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Social hierarchy is a fact of life for many animals. Navigating social hierarchy requires understanding one''s own status relative to others and behaving accordingly, while achieving higher status may call upon cunning and strategic thinking. The neural mechanisms mediating social status have become increasingly well understood in invertebrates and model organisms like fish and mice but until recently have remained more opaque in humans and other primates. In a new study in this issue, Noonan and colleagues explore the neural correlates of social rank in macaques. Using both structural and functional brain imaging, they found neural changes associated with individual monkeys'' social status, including alterations in the amygdala, hypothalamus, and brainstem—areas previously implicated in dominance-related behavior in other vertebrates. A separate but related network in the temporal and prefrontal cortex appears to mediate more cognitive aspects of strategic social behavior. These findings begin to delineate the neural circuits that enable us to navigate our own social worlds. A major remaining challenge is identifying how these networks contribute functionally to our social lives, which may open new avenues for developing innovative treatments for social disorders.
“Observing the habitual and almost sacred ‘pecking order’ which prevails among the hens in his poultry yard—hen A pecking hen B, but not being pecked by it, hen B pecking hen C and so forth—the politician will meditate on the Catholic hierarchy and Fascism.” —Aldous Huxley, Point Counter Point (1929)From the schoolyard to the boardroom, we are all, sometimes painfully, familiar with the pecking order. First documented by the Norwegian zoologist Thorleif Schjelderup-Ebbe in his PhD thesis on social status in chickens in the 1920s, a pecking order is a hierarchical social system in which each individual is ranked in order of dominance [1]. In chickens, the top hen can peck all lower birds, the second-ranking bird can peck all birds ranked below her, and so on. Since it was first coined, the term has become widely applied to any such hierarchical system, from business, to government, to the playground, to the military.Social hierarchy is a fact of life not only for humans and chickens but also for most highly social, group-living animals. Navigating social hierarchies and achieving dominance often appear to require cunning, intelligence, and strategic social planning. Indeed, the Renaissance Italian politician and writer Niccolo Machiavelli argued in his best-known book “The Prince” that the traits most useful for attaining and holding on to power include manipulation and deception [2]. Since then, the term “Machiavellian” has come to signify a person who deceives and manipulates others for personal advantage and power. 350 years later, Frans de Waal applied the term Machiavellian to social maneuvering by chimpanzees in his book Chimpanzee Politics [3]. De Waal argued that chimpanzees, like Renaissance Italian politicians, apply guile, manipulation, strategic alliance formation, and deception to enhance their social status—in this case, not to win fortune and influence but to increase their reproductive success (which is presumably the evolutionary origin of status-seeking in Renaissance Italian politicians as well).The observation that navigating large, complex social groups in chimpanzees and many other primates seems to require sophisticated cognitive abilities spurred the development of the social brain hypothesis, originally proposed to explain why primates have larger brains for their body size than do other animals [4],[5]. Since its first proposal, the social brain hypothesis has accrued ample evidence endorsing the connections between increased social network complexity, enhanced social cognition, and larger brains. For example, among primates, neorcortex size, adjusted for the size of the brain or body, varies with group size [6],[7], frequency of social play [8], and social learning [9].Of course, all neuroscientists know that when it comes to brains, size isn''t everything [10]. Presumably social cognitive functions required for strategic social behavior are mediated by specific neural circuits. Here, we summarize and discuss several recent discoveries, focusing on an article by Noonan and colleagues in the current issue, which together begin to delineate the specific neural circuits that mediate our ability to navigate our social worlds.Using structural magnetic resonance imaging (MRI), Bickart and colleagues showed that the size of the amygdala—a brain nucleus important for emotion, vigilance, and rapid behavioral responses—is correlated with social network size in humans [11]. Subsequent studies showed similar relationships for other brain regions implicated in social function, including the orbitofrontal cortex [12] and ventromedial prefrontal cortex [13]. Indeed, one study even found an association between grey matter density in the superior temporal sulcus (STS) and temporal gyrus and an individual''s number of Facebook friends [14]. Collectively, these studies suggest that the number and possibly the complexity of relationships one maintains varies with the structural organization of a specific network of brain regions, which are recruited when people perform tests of social cognition such as recognizing faces or inferring others'' mental states [15],[16]. These studies, however, do not reveal whether social complexity actively changes these brain areas through plasticity or whether individual differences in the structure of these networks ultimately determines social abilities.To address this question, Sallet and colleagues experimentally assigned rhesus macaques to social groups of different sizes and then scanned their brains with MRI [17]. The authors found significant positive associations between social network size and morphology in mid-STS, rostral STS, inferior temporal (IT) gyrus, rostral prefrontal cortex (rPFC), temporal pole, and amygdala. The authors also found a different region in rPFC that scaled positively with social rank; as grey matter in this region increased, so did the monkey''s rank in the hierarchy. As in the human studies described previously, many of these regions are implicated in various aspects of social cognition and perception [18]. These findings endorse the idea that neural plasticity is engaged in specifically social brain areas in response to the demands of the social environment, changing these areas structurally according to an individual''s experiences with others.Sallet and colleagues also examined spontaneous coactivation among these regions using functional MRI (fMRI). Measures of coactivation are thought to reflect coupling between regions [19],[20]; these measures are observable in many species [21],[22] and vary according to behavior [23],[24], genetics [25], and sex [26], suggesting that coactivation may underlie basic neural function and interaction between brain regions. The authors found that coactivation between the STS and rPFC increased with social network size and that coactivation between IT and rPFC increased with social rank. These findings show that not only do structural changes occur in these regions to meet the demands of the social environment but these structural changes mediate changes in function as well.One important question raised by the study by Sallet and colleagues is whether changes in the structure and function of social brain areas are specific outcomes of social network size or of dealing with social hierarchy. After all, larger groups offer more opportunity for a larger, more despotic pecking order. In the current volume, Noonan and colleagues address this question directly by examining the structural and functional correlates of social status in macaques independently of social group size [27]. The authors collected MRI scans from rhesus macaques and measured changes in grey matter associated with social dominance. By scanning monkeys of different ranks living in groups of different sizes, the authors were able to cleave the effects of social rank from those of social network size (Figure 1).Open in a separate windowFigure 1Brain regions in rhesus macaques related to social environment.Primary colors indicate brain regions in which morphometry tracks social network size. Pastel colors indicate brain regions in which morphometry tracks social status in the hierarchy. Regions of interest adapted from [48], overlaid on Montreal Neurological Institute (MNI) macaque template [49].The authors found a network of regions in which grey matter measures varied with social rank; these regions included the bilateral central amygdala, bilateral brainstem (between the medulla and midbrain, including parts of the raphe nuclei), and hypothalamus, which varied positively with dominance, and regions in the basal ganglia, which varied negatively with social rank. These regions have been implicated in social rank functions across a number of species [28]–[32]. Importantly, these relationships were unique to social status. There was no relationship between grey matter in these subcortical areas and social network size, endorsing a specific role in social dominance-related behavior. Nevertheless, grey matter in bilateral mid-STS and rPFC varied with both social rank and social network size, as reported previously. These findings demonstrate that specific brain areas uniquely mediate functions related to social hierarchy, whereas others may subserve more general social cognitive processes.Noonan and colleagues next probed spontaneous coactivation using fMRI to examine whether functional coupling between any of these regions varied with social status. They found that the more subordinate an animal, the stronger the functional coupling between multiple regions related to dominance. These results suggest that individual differences in social status are functionally observable in the brain even while the animal is at rest and not engaged in social behavior. These findings suggest that structural changes associated with individual differences in social status alter baseline brain function, consistent with the idea that the default mode of the brain is social [33] and that the sense of self and perhaps even awareness emerge from inwardly directed social reasoning [34].These findings resonate with previous work on the neural basis of social dominance in other vertebrates. In humans, for example, activity in the amygdala tracks knowledge of social hierarchy [28],[35] and, further, shows activity patterns that uniquely encode social rank and predict relevant behaviors [28]. Moreover, recent research has identified a specific region in the mouse hypothalamus, aptly named the “hypothalamic attack area” [36],[37]. Stimulating neurons in this area immediately triggers attacks on other mice and even an inflated rubber glove, while inactivating these neurons suppresses aggression [38]. In the African cichlid fish Haplochromis burtoni, a change in the social status of an individual male induces a reversible change in the abundance of specialized neurons in the hypothalamus that communicate hormonally with the pituitary and gonads [39]. Injections of this hormone in male birds after an aggressive territorial encounter amplifies the normal subsequent rise in testosterone [40]. Serotonin neurons in the raphe area of the brainstem also contribute to dominance-related behaviors in fish [29],[31] and aggression in monkeys [41].Despite these advances, there are still gaps in our understanding of how these circuits mediate status-related behaviors. Though regions in the amygdala, brainstem, and hypothalamus vary structurally and functionally with social rank, it remains unknown precisely how they contribute to or respond to social status. For example, though amygdala function and structure correlates with social status in both humans and nonhuman primates [27],[28],[35],[42], it remains unknown which aspects of dominance this region contributes to or underlies. One model suggests that the amygdala contributes to learning or representing one''s own status within a social hierarchy [28],[35]. Alternatively, the amygdala could contribute to behaviors that support social hierarchy, including gaze following [43] and theory of mind [44]. Lastly, the amygdala could contribute to social rank via interpersonal behaviors or personality traits, such as aggression [45], grooming [45], or fear responses [46],[47]. Future work will be critical to determine how signals in these regions relate to social status; direct manipulation of these regions, possibly via microstimulation, larger-scale brain stimulation (e.g., transcranial magnetic stimulation and transcranial direct current stimulation), or temporary lesions, will be critical to better understand these relationships.The work by Noonan and colleagues suggests new avenues for exploring how the brain both responds to and makes possible social hierarchy in nonhuman primates and humans. The fact that the neural circuits mediating dominance and social networking behavior can be identified and measured from structural and functional brain scans even at rest suggests the possibility that similar measures can be made in humans. Although social status is much more complex in people than it is in monkeys or fish, it is just as critical for us and most likely depends on shared neural circuits. Understanding how these circuits work, how they develop, and how they respond to the local social environment may help us to understand and ultimately treat disorders, like autism, social anxiety, or psychopathy, that are characterized by impaired social behavior and cognition. 相似文献
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From bacteria to multicellular animals, most organisms exhibit declines in survivorship or reproductive performance with increasing age (“senescence”) [1],[2]. Evidence for senescence in clonal plants, however, is scant [3],[4]. During asexual growth, we expect that somatic mutations, which negatively impact sexual fitness, should accumulate and contribute to senescence, especially among long-lived clonal plants [5],[6]. We tested whether older clones of Populus tremuloides (trembling aspen) from natural stands in British Columbia exhibited significantly reduced reproductive performance. Coupling molecular-based estimates of clone age with male fertility data, we observed a significant decline in the average number of viable pollen grains per catkin per ramet with increasing clone age in trembling aspen. We found that mutations reduced relative male fertility in clonal aspen populations by about 5.8×10−5 to 1.6×10−3 per year, leading to an 8% reduction in the number of viable pollen grains, on average, among the clones studied. The probability that an aspen lineage ultimately goes extinct rises as its male sexual fitness declines, suggesting that even long-lived clonal organisms are vulnerable to senescence. 相似文献
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Vaughn S. Cooper 《PLoS biology》2014,12(2)
Examples of ecological specialization abound in nature but the evolutionary and genetic causes of tradeoffs across environments are typically unknown. Natural selection itself may favor traits that improve fitness in one environment but reduce fitness elsewhere. Furthermore, an absence of selection on unused traits renders them susceptible to mutational erosion by genetic drift. Experimental evolution of microbial populations allows these potentially concurrent dynamics to be evaluated directly, rather than by historical inference. The 50,000 generation (and counting) Lenski Long-Term Evolution Experiment (LTEE), in which replicate E. coli populations have been passaged in a simple environment with only glucose for carbon and energy, has inspired multiple studies of their potential specialization. Earlier in this experiment, most changes were the side effects of selection, both broadening growth potential in some conditions and narrowing it in others, particularly in assays of diet breadth and thermotolerance. The fact that replicate populations experienced similar losses suggested they were becoming specialists because of tradeoffs imposed by selection. However a new study in this issue of PLOS Biology by Nicholas Leiby and Christopher Marx revisits these lines with powerful new growth assays and finds a surprising number of functional gains as well as losses, the latter of which were enriched in populations that had evolved higher mutation rates. Thus, these populations are steadily becoming glucose specialists by the relentless pressure of mutation accumulation, which has taken 25 years to detect. More surprising, the unpredictability of functional changes suggests that we still have much to learn about how the best-studied bacterium adapts to grow on the best-studied sugar.The wonder of biological diversity belies a puzzling subtext. Species are defined as much by their limits as their capabilities. Very few species in our common vernacular tolerate life in a wide range of environments, and those that do—the Norway rat, say—are not generally appealing. More often, we celebrate specialization to a particular condition: for example, orchid epiphytes growing tenuously in the cloud forest, only a subtle climate shift from extinction. Even grade school natural history teaches us that species are often unfit when living beyond their natural range.So it comes as a surprise that the causes of this rampant ecological specialization are poorly understood. “Use it or lose it,” but why? One common explanation is that natural selection tends to favor traits that simultaneously enhance fitness in one environment but compromise fitness elsewhere. This selective process is known as “antagonistic pleiotropy.” Another explanation is that a selective shadow falls upon unused traits, rendering them susceptible to mutational erosion by random genetic drift. This neutral process is known as “mutation accumulation” (Figure 1). These processes inevitably co-occur, and can be enhanced by the hybrid dynamic of genetic hitchhiking, in which neutral mutations affecting unused functions become linked to different mutations under positive selection. In most cases, the functional decay of a species can only be studied retrospectively, and distinguishing the roles of antagonistic pleiotropy and mutation accumulation is hampered by weak historical inference. Did selection, or an absence of selection, produce the blind cavefish [1]? There is little controversy that the sum of these dynamics can produce specialists, but their timing and relative importance is an open question.Open in a separate windowFigure 1Hypothetical dynamics of fitness in foreign environments by pleiotropy or mutation accumulation during long-term adaptation.Prolonged adaptation to one environment leads to decelerating fitness gains in the selective environment (solid black line), as beneficial mutations become limiting. Consequences of this adaptation for fitness in other environments may take different forms. No net change may occur if beneficial mutations generate no or inconsistent side effects (neutrality). However, the same mutations responsible for adaptation may also increase fitness in other environments (synergistic pleiotropy, dotted line), may decrease fitness in foreign environments at an equivalent rate if antagonistic effects correlate with selected effects (antagonistic pleiotropy, dotted line), or may decrease fitness at an increasing rate if subsequent mutations generate greater tradeoffs (antagonistic pleiotropy, dashed and dotted line). The uncertainty of the form of pleiotropic effects reflects a general lack of understanding of how mutations interact to affect fitness, particularly over the long term. Mutation accumulation (MA) in traits hidden from selection is expected to reduce fitness randomly but linearly on average, more slowly during evolution at a low mutation rate (MA, low U) or more rapidly at a high mutation rate (MA, high U). Evidence of all processes is now evident in this latest study of the evolution of diet breadth in the LTEE [20].The study of “evolution in action” using model experimental populations of rapidly reproducing organisms allows researchers to quantify both adaptation and any functional declines simultaneously. This approach is especially powerful when samples of evolving populations can be stored inanimate and studied at a later time under various conditions. Perhaps the best example of this approach is Richard Lenski''s Long-Term Evolution Experiment (LTEE), in which 12 populations of E. coli have been grown under simple conditions for more than 25 years and 50,000 generations [2],[3].When as a graduate student I wondered aloud whether the LTEE lines had become specialists, a colleague remarked: “Of course! You''ve selected for streamlined E. coli that have scuttled unused functions.” But with only a small amount of glucose as the sole carbon source available to the ancestor (the innovation by one population of using citrate for growth more than 30,000 generations in the future notwithstanding [4]), all anabolic pathways to construct new cells remain under strong selection to preserve their function. Moreover, because some catabolic reactions use the same intermediates as anabolic pathways (a form of pleiotropy) [5], growth on alternative carbon sources may be nonetheless preserved. Thus, we wondered whether the physiology of E. coli might actually prove to be robust during long-term evolution on glucose alone.Over the first 2,000 generations, the LTEE lines gained more often than lost fitness across a range of different environments [6]. In addition, a high-throughput screen of cellular respiration (Biolog) for the best-studied clone from these lines showed 171 relative gains and only 32 losses [7]. Even these losses in substrate respiration did not translate to reduced fitness versus the ancestor; rather, the evolved clone was simply relatively worse in the foreign resources than in glucose [7]. Evidently, each of the five beneficial mutations found in this early clone was broadly beneficial and imparted few tradeoffs [8]. Generalists rather than specialists were the rule.Between 2,000 and 20,000 generations, fitness losses in foreign conditions became more obvious but not always consistent. Some lines became less fit than the ancestor in a dilute complex medium (LB) [9], all lines grew worse at high (>40°C) and low (<20°C) temperature [10], and all lines became sensitive to the resource concentration in their environment, even for glucose [9]. Did subsequent beneficial mutations cause these tradeoffs (antagonistic pleiotropy), or did other, neutral or slightly harmful mutations accumulate by drift (Figure 1)? We must consider the population genetic dynamics of these LTEE populations. The hallmark of neutral theory [11] is that mutations with no effect in the selective environment should become fixed in the population at the rate of mutation. For the ancestor of this experiment, the mutation rate is ∼10−3 per genome per generation [12],[13], so only a handful of neutral mutations would have fixed by the time tradeoffs became evident, and would not likely explain the early specialization.However, an important extension of neutral theory is that slightly harmful mutations—those whose effects are roughly the inverse of the population size or below, 1/N—can also be fixed by drift [14]. Millions of slightly deleterious mutations were produced in these populations, which cycled between 5×106 and 5×108 cells each day. Might these mutations account for tradeoffs over the first 10–20,000 generations? In small populations, the effect of these mutations can be substantial, which explains why bottlenecked populations may experience fitness declines or even the genome erosion frequently seen in bacterial endosymbionts [15]. But in the large LTEE populations, most deleterious mutations are weeded out by selection and only those with the slightest effects may accumulate over very long time scales. Thus, because these early losses tended to occur when adaptation in the selective environment was most rapid, and because the randomness and rarity of mutation accumulation should not produce parallel changes over these time scales, early specialization is best explained by antagonistic pleiotropy [9],[10].Later in the LTEE, elevated mutation rates began to evolve in certain lines, resulting in a fundamental change in the population genetic environment [16],[17] that should increase the rate of functional decay in unused, essentially neutral functions. These mutator populations tended to perform worse in multiple environments, and in theory should continue to specialize more rapidly by accelerated mutation accumulation. As a first test, we used Biolog plates to assay respiration on 95 different carbon sources over the first 20,000 generations [18]. Although mutators tended to exhibit a reduced breadth of function in this assay, the difference was not statistically significant [18]. Rather, a surprising number of losses of function were shared among replicate lines, and we took this parallelism as further support of antagonistic pleiotropy driven by selection for common sets of adaptive mutations.Here the LTEE offers its greatest advantage: more time, both for evolution and innovative research. Over subsequent generations, mutator lines should continue to accumulate greater mutational load by drift and hence become more specialized than lines retaining the low ancestral rate. Genomic sequences of the evolved lines now have confirmed this increased mutational load [3],[19] in the six of 12 lines that are now mutators [16]. In this issue, Leiby and Marx [20] have readdressed these questions by retracing old steps, applying the prior Biolog assays to lines spanning 50,000 generations of evolution, and by pioneering new high-throughput assays of fitness in many resources. Somewhat surprisingly, these methods disagree and challenge the reliability of Biolog data as a fitness proxy. As a proprietary measure of cellular respiration, it can demonstrate major functional shifts but is less reliable than growth rate as a fitness parameter.More importantly, Leiby and Marx provide clear evidence that niche breadth in the LTEE was shaped by both mutation accumulation and pleiotropy. Growth rates actually increased on several resources, and hence the pleiotropic effects of adaptation to glucose were synergistic, broadening functionality particularly over the first 20,000 generations, as well as antagonistic, producing fewer tradeoffs than previously thought [20]. Pleiotropic effects were also somewhat unpredictable: a sophisticated flux-balance analysis [21] of foreign substrates did not reveal more gains for resources similar to glucose or losses for dissimilar resources. Some early losses linked to selection (maltose, galactose, serine) [6] became complete, but also subtle gains of function for dicarboxylic acid metabolism, perhaps related to growth on metabolic byproducts, became amplified. The most striking pattern was that mutator populations became specialists, diminished for many functions owing to their greater mutational burden, and this only became evident after 50,000 generations in a single resource. These convergent functional losses were not caused by selection, as is often argued, but rather by an absence of selection in the face of mutational pressure. Mutational decay by genetic drift takes a long time, and it will take much longer for the non-mutator lines, it seems.Although Leiby and Marx [20] correctly emphasize the importance of truly long-term selection combined with deficient DNA repair to reveal effects of mutation accumulation, decay has been witnessed in other systems undergoing regular population bottlenecks over shorter time scales [22],[23]. Antagonistic pleiotropy can also reveal its effects much more rapidly than was seen in the LTEE, especially when selection discriminates among discrete fitness features in a heterogeneous environment, such as in the colonization of a new landscape [24],[25]. What this study uniquely illustrates is the unpredictability of pleiotropic effects of adaptation to a simple environment, which in turn shows how chance draws from a distribution of contending beneficial mutations may produce divergent outcomes, ranging from generalists to specialists. A sample of the first mutants competing to prevail in the LTEE system showed variable niche breadth [26] so perhaps we should not be surprised that the footprints of these large-effect mutations endure. Further study of the precise mechanisms by which different mutations produce more fit offspring will teach us more about the origins of diversity that beguile us. We can also gain a broader perspective on the longstanding tension between chance and necessity [27]—a motivator of the LTEE—by focusing more on what is unnecessary, such as how organisms grow in foreign environments. Often insight comes from studying at the margins of a problem, and here, the limits to the growth of these bacteria have allowed us to focus more on how exactly they have accomplished their most essential tasks. 相似文献
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Simon Robin Evans 《PLoS biology》2016,14(4)
It was recently proposed that long-term population studies be exempted from the expectation that authors publicly archive the primary data underlying published articles. Such studies are valuable to many areas of ecological and evolutionary biological research, and multiple risks to their viability were anticipated as a result of public data archiving (PDA), ultimately all stemming from independent reuse of archived data. However, empirical assessment was missing, making it difficult to determine whether such fears are realistic. I addressed this by surveying data packages from long-term population studies archived in the Dryad Digital Repository. I found no evidence that PDA results in reuse of data by independent parties, suggesting the purported costs of PDA for long-term population studies have been overstated.Data are the foundation of the scientific method, yet individual scientists are evaluated via novel analyses of data, generating a potential conflict of interest between a research field and its individual participants that is manifested in the debate over access to the primary data underpinning published studies [1–5]. This is a chronic issue but has become more acute with the growing expectation that researchers publish the primary data underlying research reports (i.e., public data archiving [PDA]). Studies show that articles publishing their primary data are more reliable and accrue more citations [6,7], but a recent opinion piece by Mills et al. [2] highlighted the particular concerns felt by some principal investigators (PIs) of long-term population studies regarding PDA, arguing that unique aspects of such studies render them unsuitable for PDA. The "potential costs to science" identified by Mills et al. [2] as arising from PDA are as follows:
- Publication of flawed research resulting from a "lack of understanding" by independent researchers conducting analyses of archived data
- Time demands placed on the PIs of long-term population studies arising from the need to correct such errors via, e.g., published rebuttals
- Reduced opportunities for researchers to obtain the skills needed for field-based data collection because equivalent long-term population studies will be rendered redundant
- Reduced number of collaborations
- Inefficiencies resulting from repeated assessment of a hypothesis using a single dataset
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Daven C. Presgraves 《PLoS biology》2013,11(2)
The modern evolutionary synthesis codified the idea that species exist as distinct entities because intrinsic reproductive barriers prevent them from merging together. Understanding the origin of species therefore requires understanding the evolution and genetics of reproductive barriers between species. In most cases, speciation is an accident that happens as different populations adapt to different environments and, incidentally, come to differ in ways that render them reproductively incompatible. As with other reproductive barriers, the evolution and genetics of interspecific hybrid sterility and lethality were once also thought to evolve as pleiotripic side effects of adaptation. Recent work on the molecular genetics of speciation has raised an altogether different possibility—the genes that cause hybrid sterility and lethality often come to differ between species not because of adaptation to the external ecological environment but because of internal evolutionary arms races between selfish genetic elements and the genes of the host genome. Arguably one of the best examples supporting a role of ecological adaptation comes from a population of yellow monkey flowers, Mimulus guttatus, in Copperopolis, California, which recently evolved tolerance to soil contaminants from copper mines and simultaneously, as an incidental by-product, hybrid lethality in crosses with some off-mine populations. However, in new work, Wright and colleagues show that hybrid lethality is not a pleiotropic consequence of copper tolerance. Rather, the genetic factor causing hybrid lethality is tightly linked to copper tolerance and spread to fixation in Copperopolis by genetic hitchhiking.New species arise when populations gradually evolve intrinsic reproductive barriers to interbreeding with other populations [1]–[3]. Two species can be reproductively isolated from one another in ways that prevent the formation of interspecific hybrids—the species may, for instance, have incompatible courtship signals or occupy different ecological habitats. Two species can also be reproductively isolated from one another if interspecific hybrids are formed but are somehow unfit—the hybrids may be sterile, inviable, or may simply fall between parental ecological niches. All forms of reproductive isolation limit the genetic exchange between species, preventing their fusion and facilitating their further divergence. Understanding the genetic and evolutionary basis of speciation—a major cause of biodiversity—therefore involves understanding the genetics and evolutionary basis of the traits that mediate reproductive isolation.Most reproductive barriers arise as incidental by-products of selection—either ecological adaptation or sexual selection. For these cases, the genetic basis of speciation is, effectively, the genetics of adaptation. But hybrid sterility and lethality have historically posed two special problems. Darwin [4] devoted an entire chapter of his Origin of Species to the first problem: as the sterility or lethality of hybrids provides no advantage to parents, how could the genetic factors involved possibly evolve by natural selection? The second problem was recognized much later [5], after the rediscovery of Mendelian genetics: if two species (with genotypes AA and aa) produce, say, sterile hybrids (Aa) due to an incompatibility between the A and a alleles, then how could, e.g., the AA genotype have evolved from an aa ancestor in the first place without passing through a sterile intermediate genotype (Aa)? Not only does natural selection not directly favor the evolution of hybrid sterility or lethality, but there is reason to believe natural selection positively prevents its evolution.Together these problems stymied evolutionists and geneticists for decades. T.H. Huxley [6] and William Bateson [5], writing decades apart, each branded the evolution of hybrid sterility one of the most serious challenges for a then-young evolutionary theory. Darwin had, in fact, offered a simple solution to the first problem. Namely, hybrid sterility and lethality are not advantageous per se but rather “incidental on other acquired differences" [4]. Then Bateson [5], in a few short, forgotten lines solved the second problem (see [7]). Later, Dobzhansky [2] and Muller [8] would arrive at the same solution, showing that hybrid sterility or lethality could evolve readily, unopposed by natural selection, under a two-locus model with epistasis. In particular, they imagined that separate populations diverge from a common ancestor (genotype aabb), with the A allele becoming established in one population (AAbb) and the B allele in the other (aaBB); while A and B alleles must function on their respective genetic backgrounds, there is no guarantee that the A and B alleles will be functionally compatible with one another. Hybrid sterility and lethality most likely result from incompatible complementary genetic factors that disrupt development when brought together in a common hybrid genome. Dobzhansky [2] and Muller [8] could point to a few supporting data in fish, flies, and plants. Notably, like Darwin, neither speculated on the forces responsible for the evolution of the genetic factors involved.Today, there is no doubt that the Dobzhansky-Muller model is correct, as the data for incompatible complementary genetic factors is now overwhelming [1],[9]. In the last decade, a fast-growing number of speciation genes involved in these genetic incompatibilities have been identified in mice, fish, flies, yeast, and plants [9]–[11]. Perhaps not surprisingly, these speciation genes often have histories of recurrent, adaptive protein-coding sequence evolution [10],[11]. The signature of selection at speciation genes has been taken by some as tacit evidence for the pervasive role of ecological adaptation in speciation, including the evolution of hybrid sterility and lethality [12]. What is surprising, however, from the modern molecular analysis of speciation genes is how often their rapid sequence evolution and functional divergence seems to have little to do with adaptation to external ecological circumstances. Instead, speciation genes often (but not always [9]–[11]) seem to evolve as by-products of evolutionary arms races between selfish genetic elements—e.g., satellite DNAs [13],[14], meiotic drive elements [15], cytoplasmic male sterility factors [16]—and the host genes that regulate or suppress them [9]–[11],[17]. The notion that selfish genes are exotic curiosities is now giving way to a realization that selfish genes are common and diverse, each generation probing for transmission advantages at the expense of their bearers, fueling evolutionary arms races and, not infrequently, contributing to the genetic divergence that drives speciation. Indeed, the case has become so strong that examples of hybrid sterility and lethality genes that have evolved in response to ecological challenges (other than pathogens) appear to be the exception [9],[11],[17].Perhaps the most clear-cut case in which a genetic incompatibility seems to have evolved as a by-product of ecological adaptation comes from populations of the yellow monkey flower, Mimulus guttatus, from Copperopolis (California, U.S.A.). In the last ∼150 years, the Copperopolis population has evolved tolerance to the tailings of local copper mines (Figure 1). These copper-tolerant M. guttatus plants also happen to be partially reproductively isolated from many off-mine M. guttatus plants, producing hybrids that suffer tissue necrosis and death. In classic work, Macnair and Christie showed that copper tolerance is controlled by a single major factor [18] and hybrid lethality, as expected under the Dobzhansky-Muller model, by complementary factors [19]. Surprisingly, in crosses between tolerant and nontolerant plants, hybrid lethality perfectly cosegregates with tolerance [19],[20]. The simplest explanation is that the copper tolerance allele that spread to fixation in the Copperopolis population also happens to cause hybrid lethality as a pleiotropic by-product. The alternative explanation is that the copper tolerance and hybrid lethality loci happen to be genetically linked; when the copper tolerance allele spread to fixation in Copperopolis, hybrid lethality hitchhiked to high frequency along with it [20]. But with 2n = 28 chromosomes, the odds that copper tolerance and hybrid lethality alleles happen to be linked would seem vanishingly small [20].Open in a separate windowFigure 1Yellow monkey flowers (Mimulus guttatus) growing in the heavy-metal contaminated soils of copper-mine tailings.In this issue, Wright and colleagues [21] revisit this classic case of genetic incompatibility as a by-product of ecological adaptation. They make two discoveries, one genetic and the other evolutionary. By conducting extensive crossing experiments and leveraging the M. guttatus genome sequence (www.mimulusevolution.org), Wright et al. [21] map copper tolerance and hybrid necrosis to tightly linked but genetically separable loci, Tol1 and Nec1, respectively. Hybrid lethality is not a pleiotropic consequence of copper tolerance. Instead, the tolerant Tol1 allele spread to fixation in Copperopolis, and the tightly linked incompatible Nec1 allele spread with it by genetic hitchhiking. In a turn of bad luck, the loci happen to fall in a heterochromatic pericentric region, where genome assemblies are often problematic, putting identification of the Tol1 and Nec1 genes out of immediate reach. Wright et al. [21] were, however, able to identify linked markers within ∼0.3 cM of Tol1 and place Nec1 within a 10-kb genomic interval that contains a Gypsy3 retrotransposon, raising two possibilities. First, the Gypsy3 element is unlikely to cause hybrid lethality directly; instead, as transposable elements are often epigenetically silenced in plants, it seems possible that the Nec1-associated Gypsy3 is silenced with incidental consequences for gene expression on a gene (or genes) in the vicinity [22]. Second, although the Nec1 interval is 10-kb in the reference genome of M. guttatus, it could be larger in the (not-yet-sequenced) Copperopolis population, perhaps harboring additional genes.With Tol1 and Nec1 mapped near and to particular genomic scaffolds, respectively, Wright et al. were able to investigate the evolutionary history of the genomic region. Given the clear adaptive significance of copper tolerance in Copperopolis plants, we might expect to see the signatures of a strong selective sweep in the Tol1 region—a single Tol1 haplotype may have spread to fixation so quickly that all Copperopolis descendant plants bear the identical haplotype and thus show strongly reduced population genetic variability in the Tol1-Nec1 region relative to the rest of the genome [23],[24]. After the selective sweep is complete, variability in the region ought to recover gradually as new mutations arise and begin to fill out the mutation-drift equilibrium frequency spectrum expected for neutral variation in the Copperopolis population [25],[26]. Given that Tol1 reflects an adaptation to mine tailings established just ∼150 generations ago, there would have been little time for such a recovery. And yet, while Wright et al. find evidence of moderately reduced genetic variability in the Tol1-Nec1 genomic region, the magnitude of the reduction is hardly dramatic relative to the genome average.How, then, is it possible that the Tol1-Nec1 region swept to fixation in Copperopolis in fewer than ∼150 generations and yet left no strong footprint of a hitchhiking event? One possibility is that rather than a single, unique Tol1-Nec1 haplotype contributing to fixation, causing a “hard sweep," multiple Tol1-Nec1 haplotypes sampled from previously standing genetic variation contributed to fixation, causing a “soft sweep" [27]. A soft sweep would be plausible if Tol1 and Nec1 both segregate in the local off-mine ancestral population and if the two were, coincidentally, found on the same chromosome more often than expected by chance (i.e., in linkage disequilibrium). Then, after the copper mines were established, multiple plants with multiple Tol1 haplotypes (and, by association, Nec1) could have colonized the newly contaminated soils of the mine tailings. Tol1 segregates at ∼9% in surrounding populations, suggesting that standing genetic variation for copper tolerance may well have been present in the ancestral populations.Two big questions remain for the Tol1-Nec1 story, and both would be readily advanced by identification of Tol1 and Nec1. The first question concerns the history of Tol1 haplotypes in Copperopolis and surrounding off-mine populations. As Nec1-mediated hybrid lethality is incomplete, the ∼9% Tol1 frequency in surrounding populations could reflect its export via gene flow from the Copperopolis populations. Conversely, if there was a soft sweep from standing Tol1 variation in surrounding off-mine populations, then Tol1 and Nec1 may still be in linkage disequilibrium in those populations (assuming ∼150 years of recombination has not broken up the association). Resolving these alternative possibilities is a matter of establishing the history of movement of Tol1 haplotypes into or out of the Copperopolis population. The soft sweep scenario, if correct, presents a population genetics puzzle: during the historical time that mutations accumulated among the multiple tolerant but incompatible Tol1-Nec1 haplotypes in the ancestral off-mine populations, why did recombination fail to degrade the association, giving rise to tolerant but compatible haplotypes?The second question concerns the identity of Nec1 (or if it really is a Gypsy3 element, the identity of the nearby gene whose expression is disrupted as a consequence). The answer bears on one of the new emerging generalizations about genetic incompatibilities in plants [9]. Recently, Bomblies and Weigel [28] synthesized a century''s worth of observations on the commonly seen necrosis phenotype in plant hybrids and, based on their own genetic analyses in Arabidopsis
[29], suggested that many of these cases may have a common underlying basis: incompatibilities between plant pathogen resistance genes can cause autoimmune responses that result in tissue necrosis and hybrid lethality. Hybrid necrosis, indeed, appears to involve pathogen resistance genes across multiple plants groups [9],[28]. It remains to be seen if the Nec1-mediated lethality provides yet another instance. 相似文献
9.
10.
An intricate network of innate and immune cells and their derived mediators function in unison to protect us from toxic elements and infectious microbial diseases that are encountered in our environment. This vast network operates efficiently by use of a single cell epithelium in, for example, the gastrointestinal (GI) and upper respiratory (UR) tracts, fortified by adjoining cells and lymphoid tissues that protect its integrity. Perturbations certainly occur, sometimes resulting in inflammatory diseases or infections that can be debilitating and life threatening. For example, allergies in the eyes, skin, nose, and the UR or digestive tracts are common. Likewise, genetic background and environmental microbial encounters can lead to inflammatory bowel diseases (IBDs). This mucosal immune system (MIS) in both health and disease is currently under intense investigation worldwide by scientists with diverse expertise and interests. Despite this activity, there are numerous questions remaining that will require detailed answers in order to use the MIS to our advantage. In this issue of PLOS Biology, a research article describes a multi-scale in vivo systems approach to determine precisely how the gut epithelium responds to an inflammatory cytokine, tumor necrosis factor-alpha (TNF-α), given by the intravenous route. This article reveals a previously unknown pathway in which several cell types and their secreted mediators work in unison to prevent epithelial cell death in the mouse small intestine. The results of this interesting study illustrate how in vivo systems biology approaches can be used to unravel the complex mechanisms used to protect the host from its environment.Higher mammals have evolved a unique mucosal immune system (MIS) in order to protect the vast surfaces bathed by external secretions (which may exceed 300 m2 in humans) that are exposed to a rather harsh environment. The first view of the MIS is a single-layer epithelium covered by mucus and antimicrobial products and fortified by both innate and adaptive components of host defense (Figure 1). To this, we can add a natural microbiota that lives in different niches, i.e., the distal small intestine and colon, the skin, the nasal and oral cavities, and the female reproductive tract. The largest microbial population can reach ∼1012 bacteria/cm3 and occurs in the human large intestine [1]–[3]. This large intestinal microbiota includes over 1,000 bacterial species and the individual composition varies from person-to-person. Other epithelial sites harbor a separate type of microbiota, including the mouth, nose, skin, and other wet mucosal surfaces, that contributes to the host; in turn, the host benefits its microbial co-inhabitants. Gut bacteria grow by digesting complex carbohydrates, proteins, vitamins, and other components for absorption by the host, which in return rewards the microbiota by developing a natural immunity and tolerance (reviewed in [4]–[7]). Finally, the host microbiota influences the development and maturation of cells within lymphoid tissues of the MIS [8],[9].Open in a separate windowFigure 1The gut, nasal, upper respiratory and salivary, mammary, lacrimal, and other glands consist of a single layered epithelium.Projections of villi in the GI tract consist mainly of columnar epithelial cells (ECs), with other types including goblet and Paneth cells. Goblet cells exhibit several functions including secretion of mucins, which form a thick mucus covering. Paneth cells secrete chemokines, cytokines, and anti-microbial peptides (AMPs) termed α-defensins.Mucosal epithelial cells (ECs) are of central importance in host defense by providing both a physical barrier and innate immunity. For example, goblet cells secrete mucus, which forms a dense, protective covering for the entire epithelium (Figure 1). Peristalsis initiated by the brush border of gastrointestinal (GI) tract ECs allows food contents to be continuously digested and absorbed as it passes through the gut. In the upper respiratory (UR) tract, ciliated ECs capture inhaled, potentially toxic particles, and their beating moves them upward to expel them, thereby protecting the lungs. Damaged, infected, or apoptotic ECs in the GI tract move to the tips of villi and are excreted; newly formed ECs arise in the crypt region and continuously migrate upward. Paneth cells in crypt regions of the GI tract produce anti-microbial peptides (AMPs), or α-defensins, while ECs produce β-defensins [10],[11] for host protection (Figure 1). A major resident cell component of the mucosal epithelium are intraepithelial lymphocytes (IELs). The IELs consist of various T cell subsets that interact with ECs in order to maintain normal homeostasis [12]. Regulation is bi-directional, since ECs can also influence IEL T cell development and function [12]–[14].The MIS, simply speaking, can be separated into inductive and effector sites based upon their anatomical and functional properties. The migration of immune cells from mucosal inductive to effector tissues via the lymphatic system is the cellular basis for the immune response in the GI, the UR, and female reproductive tracts (Figure 2). Mucosal inductive sites include the gut-associated lymphoid tissues (GALT) and nasopharyngeal-associated lymphoid tissues (NALT), as well as less well characterized lymphoid sites (Box 1). Collectively, these comprise a mucosa-associated lymphoid tissue (MALT) network for the provision of a continuous source of memory B and T cells that then move to mucosal effector sites 13,14. The MALT contains T cell regions, B cell–enriched areas harboring a high frequency of surface IgA-positive (sIgA+) B cells, and a subepithelial area with antigen-presenting cells (APCs), including dendritic cells (DCs) for the initiation of specific immune responses (Figure 2). The MALT is covered by a subset of differentiated microfold (M) cells, ECs, but not goblet cells, and underlying lymphoid cells that play central roles in the initiation of mucosal immune responses. M cells take up antigens (Ags) from the lumen of the intestinal and nasal mucosa and transport them to the underlying DCs (Figure 2). The DCs carry Ags into the inductive sites of the Peyer''s patch or via draining lymphatics into the mesenteric lymph nodes (MLNs) for initiation of mucosal T and B cell responses (Figure 2). Retinoic acid (RA) producing DCs enhance the expression of mucosal homing receptors (α4β7 and CCR9) on activated T cells for subsequent migration through the lymphatics, the bloodstream, and into the GI tract lamina propria [15],[16]. Regulation within the MIS is critical; several T cell subsets including Th1, Th2, Th17, and Tregs serve this purpose [13],[14],[17] (Figure 2).Open in a separate windowFigure 2The mucosal immune system (MIS) is interconnected, enabling it to protect vast surface areas.This is accomplished by inductive sites of organized lymphoid tissues, e.g., in the gut the Peyer''s patches (PPs) and mesenteric lymph nodes (MLNs) comprise the GALT. Lumenal Ags can be easily sampled via M cells or by epithelial DCs since this surface is not covered by mucus due to an absence of goblet cells. Engested Ags in DCs trigger specific T and B cell responses in Peyer''s patches and MLNs. Homing of lymphocytes expressing specific receptors helps guide their eventual entry into major effector tissues, e.g., the lamina propria of the gut, the upper respiratory (UR) tract, the female reproductive tract, or acinar regions of exocrine glands. Terminal differentiation of plasma cells producing polymeric (mainly dimeric) IgA is then transported across ECs via the pIgR for subsequent release as S-IgA Abs.
Box 1. Major Inductive Sites for Mucosal Immune Responses
- GALT (gut-associated lymphoid tissues)
- Peyer''s patches (PPs)
- Mesenteric lymph nodes (MLNs)
- Isolated lymphoid follicles (ILFs)
- NALT (nasopharyngeal-associated lymphoid tissues)
- Tonsils/adenoids
- Inducible bronchus-associated lymphoid tissue (iBALT)
- Cervical lymph nodes (CLNs)
- Hilar lymph nodes (HLNs)
12.
Steven A. Frank 《PLoS biology》2013,11(6)
Gene expression varies widely in cells with the same genotype and environment [1],[2]. Predicting the patterns of stochastic cellular fluctuations remains an unsolved challenge. I propose that the degree to which varying cellular components combine to determine robust phenotypes may predict the amount of variability. Microbes provide excellent experimental models to analyze the relations between robust phenotypes and stochastic variability.
This essay is part of the Challenges Series: highlighting fundamental, unifying challenges in biology.相似文献
13.
Dieter Lukas 《PLoS biology》2013,11(3)
Parents providing care to offspring face the same problem that exists in every biological system in which some individuals offer resources to others: cheaters, who exploit these benefits. In almost all species in which males contribute to parental care, females mate with multiple males. As a result, males frequently provide efforts for unrelated offspring at a cost to their own reproductive fitness. In a new study, Griffin et al. find that across a wide range of animal species, males flexibly adjust their contribution to parental care in relation to extra-pair paternity. However, adjustment is not perfect, because males are limited by the potential costs of withholding help to their own offspring, which is only outweighed if cheating occurs frequently and if providing care reduces a male''s future reproductive success. These findings illustrate how in biological systems cheater and cheated can adapt to changes in each other, preventing either one from gaining control.Whatever your personal feelings, evolutionary biologists will tell you that caring for offspring is not an easy affair. Pick up any current textbook on behavioural ecology, and you will find that the word “family” is invariably followed by the word “conflict” (e.g., [1]). Conflicts between family members arise because selection favours individuals aiming to maximize reproductive fitness, and these aims frequently collide because selection pressures differ even among related individuals [2]–[4]. Offspring can improve their reproductive fitness by obtaining the maximal amount of investment from both of their parents. However, parents frequently provide less than the maximum because any increased investment into current offspring impacts their ability to produce additional offspring in the future. Caring for offspring in all its forms is energetically expensive and may impair a parent''s ability to have additional offspring in a variety of ways. For example, when a female of the golden egg bug (Phyllomorpha laciniata) lays her eggs on a male rather than on a plant, her offspring will have increased survival, but the father carrying the eggs has a higher risk of being eaten by a bird [5]. In bighorn sheep (Ovis canadiensis) [6], mothers are less likely to have a surviving offspring in the year after rearing a son, as males are generally heavier at birth and suckle more frequently because being larger provides an advantage when competing against other males. In European starlings (Sturnus vulgaris), males who participate less in the incubation of the offspring have a higher chance of gaining a secondary female [7].Given the costs of providing parental care, we would expect that individuals should not expend energy if they do not gain any fitness at all, as is the case when they care for offspring that are not their own [2],[8]–[10]. Individuals that are potential victims of cheating are predicted to have evolved a range of counteradaptations to reduce the risks and costs of raising unrelated offspring [11],[12] ([13].
Open in a separate windowCheaters, individuals who exploit the efforts of others, exist in a variety of contexts. In response, strategies have evolved that reduce the risks and costs of being cheated. The table describes three general strategies, shows how they apply to the context of fathers reducing the costs of caring for unrelated offspring including the finding by Griffin et al. [27], and provides examples from other contexts.Cuckoldry, individuals caring for unrelated offspring, not only occurs between members of different species, but also within a species. Caring fathers are the main victims of such intraspecies cuckoldry, because high levels of sperm competition mean that males frequently have less certainty about whether they are the parent of any given offspring [14]. Despite this uncertainty, paternal care is widespread across animals because offspring are the primary way through which individuals gain reproductive fitness [15] (Figure 1). In those fish species in which parental care occurs, it is usually the male who cares for the eggs or offspring by building a nest, fanning the eggs to ensure they receive enough oxygen, or protecting offspring against predators [16]. Males of some insect [17] and amphibian species carry the eggs on their back [18]. In most bird species, females and males share the costs of building the nest, incubating the eggs, and feeding the offspring [19]. In some monogamous and social mammals, including humans, males provide food and protection for dependent offspring [20].Open in a separate windowFigure 1Males contribute to the raising of offspring in a variety of ways in different species.In earth-boring dung beetles (Geotrupes vernalis) (1) and oyster catchers (Haematopus ostralegus) (2), males and females live in pairs and share the burdens of providing food for their offspring. In cotton-top tamarins (Saguinus oedipus) (3), males carry and protect offspring as they travel with the group while they are still being nursed by their mothers. Rainforest rocket frog (Silverstoneia flotator) (4) mothers transfer their eggs to the male before leaving, and the father cares for the developing offspring alone. Picture credit: All pictures under Creative Commons Attribution License: (1) HaPe_Gera, http://www.flickr.com/photos/hape_gera/235786194/; (2) John Haslam, http://www.flickr.com/photos/foxypar4/511910343/; (3) Qi Wei Fong, http://www.flickr.com/photos/photo-gratis/4631252697/; (4) Brian Gratwicke, http://www.flickr.com/photos/briangratwicke/5414228931/.There is relatively little consensus about the circumstances that explain why males do or do not adopt strategies to reduce the risks and costs of intraspecies cuckoldry. One well-documented and widespread male behaviour is mate guarding [21]; for example, mating induces rapid hormonal changes in the males of monogamous prairie voles (Microtus ochrogaster) that cause them to become aggressive toward conspecific strangers entering their territory and approaching the female [22]. Only a few instances of males discriminating and adjusting efforts between their own versus another male''s offspring within a brood have been reported, probably because cues that directly reflect genetic relatedness are rare [23],[24]. While individuals in many species adjust their behaviour according to how closely related they are to another individual, almost all rely on cues of familiarity; for example, long-tailed tits (Aegithalos caudatus) learn the calls of all of the individuals they encounter during their nestling phase, and they discriminate kin based on song [25]. However, such learned “familiarity cues” do not provide a way to discriminate kin from non-kin among offspring within a clutch or brood. Rather than reduce care toward specific offspring, males might alternatively decrease their total care contribution in reproductive attempts when cues indicate that they are less likely to have sired all the offspring. Until now researchers were undecided whether and in which ecological circumstances selection acts upon males to adjust care according to their average relatedness to the offspring [10],.In this issue of PLOS Biology, Griffin et al. turn to the method of phylogenetic meta-analysis to address the question of whether males show a reduction in paternal care in response to a loss of paternity [27]. Phylogenetic meta-analyses are a novel statistical approach that provide a quantitative synthesis of results across studies and across species [28],[29]. Contrary to inferences based on simple counting of the number of studies with significant results, summarizing the large number of empirical studies conducted to date in this rigorous way shows that the reduction of paternal care provided for broods that contain unrelated offspring is indeed a general biological phenomenon. Rather than being a rare behaviour that occurs under only limited circumstances, it can be found in more than 80 percent of the bird, insect, mammal, fish, and reptile species that have been studied to date. Evidence for the individual adjustment of paternal care provides an important addition to previous comparative analyses, which found that average levels of extra-pair paternity across all nests in a population covary with the average amount of care fathers provide [30],[31]. While not necessarily influenced by the same factors, differences between species ultimately derive from variation within populations, and Griffin et al.''s meta-analysis shows that variation between individual males with regard to parental effort can exist [27].In addition, phylogenetic meta-analyses allowed Griffin et al. to detect factors that have systematic effects on the strength of the adjustment of paternal care [27]. They found that reductions in paternal care are particularly high in species that have both high rates of cheating and where investment in paternal care strongly decreases the future reproductive success of males. Adjustment of paternal care will not be selected for in species with low levels of cheating because males that withhold care would risk harming their own offspring that are part of the brood. Selection for withholding care will also be weak if the benefits of gaining additional reproductive fitness are low. This suggests that male adjustment of paternal care is not limited just by an absence of reliable cues for males to detect when they have been cuckolded, but rather it is limited if the costs of potentially harming one''s own offspring outweigh the benefits of conserving energy to invest in future offspring. These findings could also inform our understanding of the evolution of interspecies cuckoldry, where it is currently unclear why individuals appear to accept parasitic cuckoo nestlings or larvae into their care in such a large number of species [13]. Based on the findings by Griffin et al. [27], future comparative studies could examine whether the frequency of cheating and the cost of caring for the stranger interact to explain the distribution of parasite acceptance.Griffin et al.''s findings raise important new questions for the evolution of paternal care. While the presented analyses focus on males, in most of the species included in their dataset both parents contribute to the raising of offspring, and the dynamics between the sexes have important consequences on mating and care strategies [32]. A previous meta-analysis found that, in birds, females increased their parental care efforts to partially compensate for lack of care by males if males were experimentally prevented from providing for the offspring, but they also found large variation across species in female response to male reductions of care [33]. Are females in species in which males show large variation in care more likely to compensate for the loss in paternal contribution by increasing their own efforts, or does male adjustment of care affect the fitness of the current offspring? There are other possible consequences of reductions in paternal care: males could be more effective at preventing cheating during the next breeding attempt, or it could influence females to seek fewer extra-pair matings. To address these questions, long-term individual-based studies are necessary to assess how the adjustment of paternal care interacts with external conditions and other behaviours of the male and his mate.Detailed studies are also necessary to understand why plasticity within individuals in extra-pair mating continues to exist. Given the high costs to males if females cheat, and the costs to females if males reduce their contribution to parental effort, why have both females and males not adjusted their behaviour to a stable strategy that maximizes fitness? Plastic adjustment of paternal care could be more likely in populations in which external factors lead to rapid changes in the frequency of cheating. For example, research in birds has shown that the occurrence of extra-pair paternity changes with fluctuations in the density of conspecifics within populations [34]. When drastic changes in density occur within the lifespan of males, individual responses that allow an adjustment of paternal care could be beneficial. If environmental changes influence the costs and benefits of mating strategies and the occurrence of extra-pair matings, reductions in paternal care could be the result of fathers reallocating energy to pursue extra-pair mating opportunities, rather than reducing the costs of caring for unrelated offspring.In general, the findings by Griffin et al. are a great illustration of the evolutionary struggle inherent in any system where some individuals provide a resource that can be exploited by others. In terms of parents providing resources to offspring, these new results show that fathers in many species adjust their behaviour flexibly to prevent and punish exploiters, while minimizing the costs to both their current and future offspring [27]. Nevertheless, they might still end up caring for unrelated offspring if selection leads females to keep extra-pair matings at a level that males will tolerate. More research is needed to understand the costs and benefits of all the actors within this system: father, mothers, and their offspring, and extra-pair males and their offspring. The long-standing study of family conflict, and the variety of solutions that have been recorded in different species, offers the opportunity to generate important insights into the evolution of exploitation and the strategies that prevent it. 相似文献
Table 1
Strategies to minimize the risks and costs of being exploited by cheaters.Strategies against cheaters | What can fathers do? | What happens in other contexts involving cheaters? |
Prevent cheaters from invading | Males frequently perform mate guarding, which ensures that they sire the offspring they are going to raise [21],[22] | Bacterial species that produce common goods disperse widely and then clonally reproduce, reducing the chance of cheater encounters [35] |
Recognize individual cheaters and shun them | In a few species, males appear able to recognize their own offspring, which ensures that benefits are not directed toward unrelated offspring [23] | Bird hosts of cuckoos and cowbirds produce colourful eggs, which increases their chance of recognizing the parasitic eggs [36] |
Adjust contributions according to cues that indicate potential returns | Males reduce paternal care when it is likely that unrelated offspring are part of the brood, which saves energy for future attempts in which no cheaters are around (study by Griffin et al. [27]) | Cleaner fish refrain from biting clients when observed by bystanders who are potential clients [37] |
15.
Glenda E. Gray Fatima Laher Tanya Doherty Salim Abdool Karim Scott Hammer John Mascola Chris Beyrer Larry Corey 《PLoS biology》2016,14(3)
In the last 15 years, antiretroviral therapy (ART) has been the most globally impactful life-saving development of medical research. Antiretrovirals (ARVs) are used with great success for both the treatment and prevention of HIV infection. Despite these remarkable advances, this epidemic grows relentlessly worldwide. Over 2.1 million new infections occur each year, two-thirds in women and 240,000 in children. The widespread elimination of HIV will require the development of new, more potent prevention tools. Such efforts are imperative on a global scale. However, it must also be recognised that true containment of the epidemic requires the development and widespread implementation of a scientific advancement that has eluded us to date—a highly effective vaccine. Striving for such medical advances is what is required to achieve the end of AIDS.In the last 15 years, antiretroviral therapy (ART) has been the most globally impactful life-saving development of medical research. Antiretrovirals (ARVs) are used with great success for both the treatment and prevention of HIV infection. In the United States, the widespread implementation of combination ARVs led to the virtual eradication of mother-to-child transmission of HIV from 1,650 cases in 1991 to 110 cases in 2011, and a turnaround in AIDS deaths from an almost 100% five-year mortality rate to a five-year survival rate of 91% in HIV-infected adults [1]. Currently, the estimated average lifespan of an HIV-infected adult in the developed world is well over 40 years post-diagnosis. Survival rates in the developing world, although lower, are improving: in sub-Saharan Africa, AIDS deaths fell by 39% between 2005 and 2013, and the biggest decline, 51%, was seen in South Africa [2].Furthermore, the association between ART, viremia, and transmission has led to the concept of “test and treat,” with the hope of reducing community viral load by testing early and initiating treatment as soon as a diagnosis of HIV is made [3]. Indeed, selected regions of the world have begun to actualize the public health value of ARVs, from gains in life expectancy to impact on onward transmission, with a potential 1% decline in new infections for every 10% increase in treatment coverage [2]. In September 2015, WHO released new guidelines removing all limitations on eligibility for ART among people living with HIV and recommending pre-exposure prophylaxis (PrEP) to population groups at significant HIV risk, paving the way for a global onslaught on HIV [4].Despite these remarkable advances, this epidemic grows relentlessly worldwide. Over 2.1 million new infections occur each year, two-thirds in women and 240,000 in children [2]. In heavily affected countries, HIV infection rates have only stabilized at best: the annualized acquisition rates in persons in their first decade of sexual activity average 3%–5% yearly in southern Africa [5–7]. These figures are hardly compatible with the international health community’s stated goal of an “AIDS-free generation” [8,9]. In highly resourced settings, microepidemics of HIV still occur, particularly among gays, bisexuals, and men who have sex with men (MSM) [10]. HIV epidemics are expanding in two geographic regions in 2015—the Middle East/North Africa and Eastern Europe/Central Asia—largely due to challenges in implementing evidence-based HIV policies and programmes [2]. Even for the past decade in the US, almost 50,000 new cases recorded annually, two-thirds among MSM, has been a stable figure for years and shows no evidence of declining [1].While treatment scale-up, medical male circumcision [11], and the implementation of strategies to prevent mother-to-child transmission [12] have received global traction, systemic or topical ARV-based biomedical advances to prevent sexual acquisition of HIV have, as yet, made limited impressions on a population basis, despite their reported efficacy. Factors such as their adherence requirements, cost, potential for drug resistance, and long-term feasibility have restricted the appetite for implementation, even though these approaches may reduce HIV incidence in select populations.Already, several trials have shown that daily oral administration of the ARV tenofovir disoproxil fumarate (TDF), taken singly or in combination with emtricitabine, as PrEP by HIV-uninfected individuals, reduces HIV acquisition among serodiscordant couples (where one partner is HIV-positive and the other is HIV-negative) [13], MSM [14], at-risk men and women [15], and people who inject drugs [16,17] by between 44% and 75%. Long-acting injectable antiretroviral agents such as rilpivirine and cabotegravir, administered every two and three months, respectively, are also being developed for PrEP. All of these PrEP approaches are dependent on repeated HIV testing and adherence to drug regimens, which may challenge effectiveness in some populations and contexts.The widespread elimination of HIV will require the development of new, more potent prevention tools. Because HIV acquisition occurs subclinically, the elimination of HIV on a population basis will require a highly effective vaccine. Alternatively, if vaccine development is delayed, supplementary strategies may include long-acting pre-exposure antiretroviral cocktails and/or the administration of neutralizing antibodies through long-lasting parenteral preparations or the development of a “genetic immunization” delivery system, as well as scaling up delivery of highly effective regimens to eliminate mother-to-child HIV transmission (Fig 1).Open in a separate windowFig 1Medical interventions required to end the epidemic of HIV.Image credit: Glenda Gray. 相似文献
16.
Ellen M. Leffler Kevin Bullaughey Daniel R. Matute Wynn K. Meyer Laure S��gurel Aarti Venkat Peter Andolfatto Molly Przeworski 《PLoS biology》2012,10(9)
Understanding why some species have more genetic diversity than others is central to the study of ecology and evolution, and carries potentially important implications for conservation biology. Yet not only does this question remain unresolved, it has largely fallen into disregard. With the rapid decrease in sequencing costs, we argue that it is time to revive it.What evolutionary forces maintain genetic diversity in natural populations? How do diversity levels relate to census population sizes (Box 1)? Do low levels of diversity limit adaptation to novel selective pressures? Efforts to address such questions spurred the rise of modern population genetics and contributed to the development of the neutral theory of molecular evolution—the null hypothesis for much of evolutionary genetics and comparative genomics [1]–[3]. Yet these questions remain wide open and, for close to two decades, have been neglected [4]. Most notably, little progress has been made to resolve a riddle first pointed out 40 years ago on the basis of allozyme data: the mysteriously narrow range of genetic diversity levels seen across taxa that vary markedly in their census population sizes [5]. This gap in our understanding is glaring, and may hamper efforts at conservation (e.g., [6]).
Box 1. Glossary
Allozymes: Allelic variants of a protein, often detected by differences in gel electrophoresis. Balancing selection: Natural selection that maintains variation longer than expected from genetic drift alone. Census population size: The actual number of individuals in a population; methods to estimate this number vary depending on the species and may involve aerial, transect, or capture/recapture counts. Diversity levels: The measure used here is the probability that a pair of randomly chosen haplotypes differ at a site. Effective population size: The size of an idealized population with some of the same properties as the actual one, e.g., the same rate of genetic drift. Under simplifying assumptions, notably a constant population size and no population structure, this parameter can be estimated from observed diversity levels, given an independent estimate of the mutation rate. Fluctuating selection: When the fitness of an allele changes over time or over space. Genetic draft: A dramatic loss of genetic variation due to strong, frequent selection at nearby sites [8]. Genetic drift: In a finite population, the loss of genetic variation due to the random sampling of gametes at each generation. Local adaptation: Adaptation to a particular environment that is not shared by the entire species. Nearly neutral theory of molecular evolution: A modification of the neutral theory, in which many mutations are slightly deleterious, rather than strictly neutral or strongly deleterious [75]. Neutral theory of molecular evolution: The theory that most genetic variation seen within populations and between species is neutral, and most mutations are either neutral or strongly deleterious [11]. Panmixia: Random mating among individuals, and hence no population structure. Phylogenetically independent contrasts: A statistical method that allows one to compare properties of species controlling for their evolutionary relationship. Purifying (negative) selection: Natural selection that favors the common, fitter allele against rare, deleterious alleles. Selection at linked sites: Selection at sites linked to the locus under consideration, which can affect the population dynamics of alleles at that locus. Silent sites: A general term for synonymous, intronic, and intergenic sites—all sites at which mutations do not change an amino acid. Variation-reducing selection: Selection that leads to a decrease in diversity at linked sites.With the recent technological revolution in sequencing, the data needed to address questions about the determinants of genetic diversity levels are now within reach. As a first step towards reviving these questions, we compile existing estimates of nuclear sequence diversity. These data are highly preliminary, but they underscore how little is known about the narrow span of diversity levels across species or why some species maintain more genetic variation than others [5],[7],[8], and they offer a glimpse of trends that may be worth pursuing. 相似文献17.
The hippocampus has unique access to neuronal activity across all of the neocortex. Yet an unanswered question is how the transfer of information between these structures is gated. One hypothesis involves temporal-locking of activity in the neocortex with that in the hippocampus. New data from the Matthew E. Diamond laboratory shows that the rhythmic neuronal activity that accompanies vibrissa-based sensation, in rats, transiently locks to ongoing hippocampal θ-rhythmic activity during the sensory-gathering epoch of a discrimination task. This result complements past studies on the locking of sniffing and the θ-rhythm as well as the relation of sniffing and whisking. An overarching possibility is that the preBötzinger inspiration oscillator, which paces whisking, can selectively lock with the θ-rhythm to traffic sensorimotor information between the rat’s neocortex and hippocampus.The hippocampus lies along the margins of the cortical mantle and has unique access to neuronal activity across all of the neocortex. From a functional perspective, the hippocampus forms the apex of neuronal processing in mammals and is a key element in the short-term working memory, where neuronal signals persist for tens of seconds, that is independent of the frontal cortex (reviewed in [1,2]). Sensory information from multiple modalities is highly transformed as it passes from primary and higher-order sensory areas to the hippocampus. Several anatomically defined regions that lie within the temporal lobe take part in this transformation, all of which involve circuits with extensive recurrent feedback connections (reviewed in [3]) (Fig 1). This circuit motif is reminiscent of the pattern of connectivity within models of associative neuronal networks, whose dynamics lead to the clustering of neuronal inputs to form a reduced set of abstract representations [4] (reviewed in [5]). The first way station in the temporal lobe contains the postrhinal and perirhinal cortices, followed by the medial and lateral entorhinal cortices. Of note, olfactory input—which, unlike other senses, has no spatial component to its representation—has direct input to the lateral entorhinal cortex [6]. The third structure is the hippocampus, which contains multiple substructures (Fig 1).Open in a separate windowFig 1Schematic view of the circuitry of the temporal lobe and its connections to other brain areas of relevance.Figure abstracted from published results [7–15]. Composite illustration by Julia Kuhl.The specific nature of signal transformation and neuronal computations within the hippocampus is largely an open issue that defines the agenda of a great many laboratories. Equally vexing is the nature of signal transformation as the output leaves the hippocampus and propagates back to regions in the neocortex (Fig 1)—including the medial prefrontal cortex, a site of sensory integration and decision-making—in order to influence perception and motor action. The current experimental data suggest that only some signals within the sensory stream propagate into and out of the hippocampus. What regulates communication with the hippocampus or, more generally, with structures within the temporal lobe? The results from studies in rats and mice suggest that the most parsimonious hypothesis, at least for rodents, involves the rhythmic nature of neuronal activity at the so-called θ-rhythm [16], a 5–10 Hz oscillation (reviewed in [17]). The origin of the rhythm is not readily localized to a single locus [10], but certainly involves input from the medial septum [17] (a member of the forebrain cholinergic system) as well as from the supramammillary nucleus [10,18] (a member of the hypothalamus). The medial septum projects broadly to targets in the hippocampus and entorhinal cortex (Fig 1) [10]. Many motor actions, such as the orofacial actions of sniffing, whisking, and licking, occur within the frequency range of the θ-rhythm [19,20]. Thus, sensory input that is modulated by rhythmic self-motion can, in principle, phase-lock with hippocampal activity at the θ-rhythm to ensure the coherent trafficking of information between the relevant neocortical regions and temporal lobe structures [21–23].We now shift to the nature of orofacial sensory inputs, specifically whisking and sniffing, which are believed to dominate the world view of rodents [19]. Recent work identified a premotor nucleus in the ventral medulla, named the vibrissa region of the intermediate reticular zone, whose oscillatory output is necessary and sufficient to drive rhythmic whisking [24]. While whisking can occur independently of breathing, sniffing and whisking are synchronized in the curious and aroused animal [24,25], as the preBötzinger complex in the medulla [26]—the oscillator for inspiration—paces whisking at nominally 5–10 Hz through collateral projections [27]. Thus, for the purposes of reviewing evidence for the locking of orofacial sensory inputs to the hippocampal θ-rhythm, we confine our analysis to aroused animals that function with effectively a single sniff/whisk oscillator [28].What is the evidence for the locking of somatosensory signaling by the vibrissae to the hippocampal θ-rhythm? The first suggestion of phase locking between whisking and the θ-rhythm was based on a small sample size [29,30], which allowed for the possibility of spurious correlations. Phase locking was subsequently reexamined, using a relatively large dataset of 2 s whisking epochs, across many animals, as animals whisked in air [31]. The authors concluded that while whisking and the θ-rhythm share the same spectral band, their phases drift incoherently. Yet the possibility remained that phase locking could occur during special intervals, such as when a rat learns to discriminate an object with its vibrissae or when it performs a memory-based task. This set the stage for a further reexamination of this issue across different epochs in a rewarded task. Work from Diamond''s laboratory that is published in the current issue of PLOS Biology addresses just this point in a well-crafted experiment that involves rats trained to perform a discrimination task.Grion, Akrami, Zuo, Stella, and Diamond [32] trained rats to discriminate between two different textures with their vibrissae. The animals were rewarded if they turned to a water port on the side that was paired with a particular texture. Concurrent with this task, the investigators also recorded the local field potential in the hippocampus (from which they extracted the θ-rhythm), the position of the vibrissae (from which they extracted the evolution of phase in the whisk cycle), and the spiking of units in the vibrissa primary sensory cortex. Their first new finding is a substantial increase in the amplitude of the hippocampal field potential at the θ-rhythm frequency—approximately 10 Hz for the data of Fig 2A—during the two, approximately 0.5 s epochs when the animal approaches the textures and whisks against it. There is significant phase locking between whisking and the hippocampal θ-rhythm during both of these epochs (Fig 2B), as compared to a null hypothesis of whisking while the animal whisked in air outside the discrimination zone. Unfortunately, the coherence between whisking and the hippocampal θ-rhythm could not be ascertained during the decision, i.e., turn and reward epochs. Nonetheless, these data show that the coherence between whisking and the hippocampal θ-rhythm is closely aligned to epochs of active information gathering.Open in a separate windowFig 2Summary of findings on the θ-rhythm in a rat during a texture discrimination task, derived from reference [32].
(A) Spectrogram showing the change in spectral power of the local field potential in the hippocampal area CA1 before, during, and after a whisking-based discrimination task. (B) Summary index of the increase in coherence between the band-limited hippocampal θ-rhythm and whisking signals during approach of the rat to the stimulus and subsequent touch. The index reports , where ɸH and ɸW are the instantaneous phase of the hippocampal and whisking signals, respectively, and averaging is over all trials and animals. (C) Summary indices of the increase in coherence between the band-limited hippocampal θ-rhythm and the spiking signal in the vibrissa primary sensory cortex (“barrel cortex”). The magnitude of the index for each neuron is plotted versus phase in the θ-rhythm. The arrows show the concentration of units around the mean phase—black arrows for the vector average across only neurons with significant phase locking (solid circles) and gray arrows for the vector average across all neurons (open and closed circles). The concurrent positions of the vibrissae are indicated. The vector average is statistically significant only for the approach (p < 0.0001) and touch (p = 0.04) epochs.The second finding by Grion, Akrami, Zuo, Stella, and Diamond [32] addresses the relationship between spiking activity in the vibrissa primary sensory cortex and the hippocampal θ-rhythm. The authors find that spiking is essentially independent of the θ-rhythm outside of the task (foraging in Fig 2C), similar to the result for whisking and the θ-rhythm (Fig 2B). They observe strong coherence between spiking and the θ-rhythm during the 0.5 s epoch when the animal approaches the textures (approach in Fig 2C), yet reduced (but still significant) coherence during the touch epoch (touch in Fig 2C). The latter result is somewhat surprising, given past work from a number of laboratories that observe spiking in the primary sensory cortex and whisking to be weakly yet significantly phase-locked during exploratory whisking [33–37]. Perhaps overtraining leads to only a modest need for the transfer of sensory information to the hippocampus. Nonetheless, these data establish that phase locking of hippocampal and sensory cortical activity is essentially confined to the epoch of sensory gathering.Given the recent finding of a one-to-one locking of whisking and sniffing [24], we expect to find direct evidence for the phase locking of sniffing and the θ-rhythm. Early work indeed reported such phase locking [38] but, as in the case of whisking [29], this may have been a consequence of too small a sample and, thus, inadequate statistical power. However, Macrides, Eichenbaum, and Forbes [39] reexamined the relationship between sniffing and the hippocampal θ-rhythm before, during, and after animals sampled an odorant in a forced-choice task. They found evidence that the two rhythms phase-lock within approximately one second of the sampling epoch. We interpret this locking to be similar to that seen in the study by Diamond and colleagues (Fig 2B) [32]. All told, the combined data for sniffing and whisking by the aroused rodent, as accumulated across multiple laboratories, suggest that two oscillatory circuits—the supramammillary nucleus and medial septum complex that drives the hippocampal θ-rhythm and the preBötzinger complex that drives inspiration and paces the whisking oscillator during sniffing (Fig 1)—can phase-lock during epochs of gathering sensory information and likely sustain working memory.What anatomical pathway can lead to phase locking of these two oscillators? The electrophysiological study of Tsanov, Chah, Reilly, and O’Mara [9] supports a pathway from the medial septum, which is driven by the supramammillary nucleus, to dorsal pontine nuclei in the brainstem. The pontine nucleus projects to respiratory nuclei and, ultimately, the preBötzinger oscillator (Fig 1). This unidirectional pathway can, in principle, entrain breathing and whisking. Phase locking is not expected to occur during periods of basal breathing, when the breathing rate and θ-rhythm occur at highly incommensurate frequencies. However, it remains unclear why phase locking occurs only during a selected epoch of a discrimination task, whereas breathing and the θ-rhythm occupy the same frequency band during the epochs of approach, as well as touch-based target selection (Fig 2A). While a reafferent pathway provides the rat with information on self-motion of the vibrissae (Fig 1), it is currently unknown whether that information provides feedback for phase locking.A seeming requirement for effective communication between neocortical and hippocampal processing is that phase locking must be achieved at all possible phases of the θ-rhythm. Can multiple phase differences between sensory signals and the hippocampal θ-rhythm be accommodated? Two studies report that the θ-rhythm undergoes a systematic phase-shift along the dorsal–ventral axis of the hippocampus [40,41], although the full extent of this shift is only π radians [41]. In addition, past work shows that vibrissa input during whisking is represented among all phases of the sniff/whisk cycle, at levels from primary sensory neurons [42,43] through thalamus [44,45] and neocortex [33–37], with a bias toward retraction from the protracted position. A similar spread in phase occurs for olfactory input, as observed at the levels of the olfactory bulb [46] and cortex [47]. Thus, in principle, the hippocampus can receive, transform, and output sensory signals that arise over all possible phases in the sniff/whisk cycle. In this regard, two signals that are exactly out-of-phase by π radians can phase-lock as readily as signals that are in-phase.What are the constraints for phase locking to occur within the observed texture identification epochs? For a linear system, the time to lock between an external input and hippocampal theta depends on the observed spread in the spectrum of the θ-rhythm. This is estimated as Δf ~3 Hz (half-width at half-maximum amplitude), implying a locking time on the order of 1/Δf ~0.3 s. This is consistent with the approximate one second of enhanced θ-rhythm activity observed in the study by Diamond and colleagues (Fig 2A) [32] and in prior work [39,48] during a forced-choice task with rodents.Does the θ-rhythm also play a role in the gating of output from the hippocampus to areas of the neocortex? Siapas, Lubenov, and Wilson [48] provided evidence that hippocampal θ-rhythm phase-locks to electrical activity in the medial prefrontal cortex, a site of sensory integration as well as decision-making. Subsequent work [49–51] showed that the hippocampus drives the prefrontal cortex, consistent with the known unidirectional connectivity between Cornu Ammonis area 1 (CA1) of the hippocampus and the prefrontal cortex [11] (Fig 1). Further, phase locking of hippocampal and prefrontal cortical activity is largely confined to the epoch of decision-making, as opposed to the epoch of sensory gathering. Thus, over the course of approximately one second, sensory information flows into and then out of the hippocampus, gated by phase coherence between rhythmic neocortical and hippocampal neuronal activity.It is of interest that the medial prefrontal cortex receives input signals from sensory areas in the neocortex [52] as well as a transformed version of these input signals via the hippocampus (Fig 1). Yet it remains to be determined if this constitutes a viable hub for the comparison of the original and transformed signals. In particular, projections to the medial prefrontal cortex arise from the ventral hippocampus [2], while studies on the phase locking of hippocampal θ-rhythm to prefrontal neocortical activity were conducted in dorsal hippocampus, where the strength of the θ-rhythm is strong compared to the ventral end [53]. Therefore, similar recordings need to be performed in the ventral hippocampus. An intriguing possibility is that the continuous phase-shift of the θ-rhythm along the dorsal to the ventral axis of the hippocampus [40,41] provides a means to encode the arrival of novel inputs from multiple sensory modalities relative to a common clock.A final issue concerns the locking between sensory signals and hippocampal neuronal activity in species that do not exhibit a continuous θ-rhythm, with particular reference to bats [54–56] and primates [57–60]. One possibility is that only the up and down swings of neuronal activity about a mean are important, as opposed to the rhythm per se. In fact, for animals in which orofacial input plays a relatively minor role compared to rodents, such a scheme of clocked yet arrhythmic input may be a necessity. In this case, the window of processing is set by a stochastic interval between transitions, as opposed to the periodicity of the θ-rhythm. This may imply that up/down swings of neuronal activity may drive hippocampal–neocortical communications in all species, with communication mediated via phase-locked oscillators in rodents and via synchronous fluctuations in bats and primates. The validity of this scheme and its potential consequence on neuronal computation remains an open issue and a focus of ongoing research. 相似文献
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Brian P. Lazzaro 《PLoS biology》2015,13(4)
Life history theory predicts that trait evolution should be constrained by competing physiological demands on an organism. Immune defense provides a classic example in which immune responses are presumed to be costly and therefore come at the expense of other traits related to fitness. One strategy for mitigating the costs of expensive traits is to render them inducible, such that the cost is paid only when the trait is utilized. In the current issue of PLOS Biology, Bajgar and colleagues elegantly demonstrate the energetic and life history cost of the immune response that Drosophila melanogaster larvae induce after infection by the parasitoid wasp Leptopilina boulardi. These authors show that infection-induced proliferation of defensive blood cells commands a diversion of dietary carbon away from somatic growth and development, with simple sugars instead being shunted to the hematopoetic organ for rapid conversion into the raw energy required for cell proliferation. This metabolic shift results in a 15% delay in the development of the infected larva and is mediated by adenosine signaling between the hematopoietic organ and the central metabolic control organ of the host fly. The adenosine signal thus allows D. melanogaster to rapidly marshal the energy needed for effective defense and to pay the cost of immunity only when infected.While sitting around the campfire, evolutionary biologists may tell tales of the Darwinian Demon [1], a mythical being who is reproductively mature upon birth, lives forever, and has infinite offspring. In the morning, though, we know that no such creature can exist. All organisms must make compromises, and fitness is determined by striking the optimal balance among traits with competing demands. This is the central premise of life history theory: adaptations are costly, and increasing investment in one trait often forces decreased investment in others [2].Phenotype plasticity provides a partial solution to this evolutionary conundrum. If traits can be called upon only when required, the costs can be mitigated during periods of disuse. There are many examples of plastic costly adaptations, including the defensive helmets grown by Daphnia species in response to the presence of predators or abiotic factors that signal risk of predation ([3,4] and references therein), the flamboyant plumage that male birds exhibit during breeding season [5], and the inducible immune systems of higher plants and animals [6,7].The very inducibility of immune systems implicitly argues for their cost. If immune defense was cost-free, it would be constantly deployed for maximum protection against pathogenic infection. However, immune reactions have frequently been inferred to be energetically demanding (e.g., [8,9]) and carry the risk of autoimmune damage (e.g., [10,11]). It may therefore be evolutionarily adaptive to minimize immune activity in the absence of infection, to rapidly ramp up immunity in response to infection, and then to quickly shut down the immune response after the infection has been managed [12,13]. A paper by Bajgar et al. in the current issue of PLOS Biology [14] uses the Drosophila–Leptopilina host–pathogen system to quantitatively measure the energetic expense of induced up-regulation of immunity, demonstrating plastic metabolic reallocation toward immune cell proliferation at the expense of nutrient storage, growth, and development.Parasitoid wasps such as Leptopilina species infect their insect larval hosts by laying an egg inside the host body cavity [15]. Unimpeded, the egg hatches into a wasp larva that feeds off and develops inside the still-living host. In the case of Leptopilina boulardi infecting Drosophila melanogaster, the infected host larva survives to enter pupation, but if the parasitization is successful, an adult wasp will ultimately emerge from the pupal case instead of an adult fruit fly. This clearly is against the interest of the D. melanogaster host, so the larval fly attempts to encapsulate the L. boulardi egg in a sheath of specialized blood cells called lamellocytes that collaborate with other cell types to suffocate the wasp egg, deprive it of nutrients, and kill it with oxidative free radicals [16]. The struggle between fly and wasp is of the highest stakes, with guaranteed death and complete loss of evolutionary fitness for the loser.Natural D. melanogaster populations are rife with genetic variation for resistance to parasitoids, and laboratory selection for as few as five generations can increase host survivorship from 1%–5% to 40%–60% (e.g., [17,18]). This evolved resistance comes at a cost, though. Larvae from evolved resistant strains have decreased capacity to compete with their unselected progenitors under crowded or nutrient-poor conditions [17,18]. The general mechanism for enhanced resistance has been recurrently revealed to be an increase in the number of circulating blood cells (hemocytes). But why are the resistant larvae outcompeted by susceptible larvae? One compelling hypothesis is that the extra investment in blood cell proliferation comes at an energetic cost to development of other tissues, a cost which may be exacerbated by a decrease in feeding rate of the selected lines [19] and that leads to impaired development under nutrient-limiting conditions. The cost can be limited, however, by producing the defensive blood cells in large numbers only when the host is infected and has need of them. Effectively achieving this requires the capacity to rapidly signal cell proliferation and to recruit the energy required for hematopoiesis from other physiological processes.Bajgar et al. [14] use a series of careful experiments to document energetic redistributions and costs associated with hemocyte proliferation and lamellocyte differentiation in D. melanogaster infected by L. boulardi. They find that parasitoid infection results in a 15% delay in host development, and that at least a fraction of this delay can be plausibly attributed to a metabolic reallocation that supports blood cell proliferation over somatic growth. Specifically, they find that dietary carbohydrates are shunted away from energetic storage and tissue development, and instead are routed to the lymph gland, where hemocytes are being produced and differentiated. The signal to activate this reallocation emanates from the lymph gland and developing hemocytes themselves in the form of secreted adenosine, which is then received and interpreted by the central metabolic control organ, the fat body. Bajgar et al. [14] are able to show in unprecedented quantitative precision, that secreted adenosine acts as a signal to rapidly trigger inducible immune defense, that this immune induction is costly at the level of individual tissues and the whole organism, and that the cost of induced defense is paid only upon infection.The D. melanogaster metabolic rearrangement after infection by L. boulardi is profound [14]. Within 6–18 hours of infection, host larvae show a strong reduction in the incorporation of dietary carbon into stored lipids and protein and an overall reduction in glycogen stores. The levels of circulating glucose and trehalose spike, with those saccharides seemingly directed to the hemocyte-producing lymph gland. Expression of glycolytic genes is suppressed in the fat body, while fat body expression of a trehalose transporter is up-regulated to promote trehalose secretion into circulation. Glucose and trehalose transporters are concomitantly up-regulated in the lymph gland and developing hemocytes to facilitate import of the circulating saccharides. Genes required for glycolysis—but not the TCA cycle—are simultaneously up-regulated in the lymph gland and nascent hemocytes to turn those sugars into quick energy under the Warburg effect [20]. The totality of the data is consistent with an interpretation that the induced hemocyte proliferation is directly costly to host larval growth as an immediate consequence of substantial energetic reallocation.This same research group had previously shown that extracellular adenosine can be used by Drosophila as a signal in regulating inflammation-like responses [21]. In the present study, they use RNAi to knock down expression of the adenosine transporter ENT2 specifically in the lymph gland and developing hemocytes. This prevention of adenosine export eliminates the spike in circulating glucose and trehalose after infection. Infected larvae with knocked down expression of ENT2 continue to allocate dietary carbon to lipid and proteins as though they were uninfected, they fail to differentiate an adequate number of lamellocytes, and they suffer reduced resistance to the parasitoid. These data firmly implicate extracellular adenosine as a critical trigger mediating the switch in energetic allocation from growth and development to induced immunity. In further support of this interpretation, larvae that are mutant for the adenosine receptor AdoR show a nearly 70% reduction relative to wild type in the number of differentiated lamellocytes after infection and consequently encapsulate the parasitoid egg at nearly 4-fold lower rates. Like the ENT2 knockdowns, AdoR mutant larvae fail to exhibit elevated levels of circulating glucose or trehalose when infected by L. boulardi, although surprisingly, the AdoR mutants do show an appropriate inhibition of glycogen storage when infected. Overall, the genetic results indicate that ENT2 protein allows secretion of adenosine from the lymph gland. This adenosine signal is received in the fat body, which then dampens energetic storage in favor of secretion and circulation of simple saccharides. These sugars are taken up by the lymph gland to rapidly facilitate hemocyte proliferation, lamellocyte differentiation, and immune defense against the parasitoid. In satisfying consistency with this model, Bajgar et al. [14] show that lamellocyte differentiation and host resistance can be partially rescued even in the absence of ENT2 or AdoR by supplementing the D. melanogaster diet with extra glucose, thereby providing the boost in the circulating saccharides required for hematopoiesis.There are key differences between studies of evolutionary tradeoffs, such as those conducted by Kraaijeveld and colleagues (e.g., [17–19]), and studies of physiological costs such as the one conducted by Bajgar et al. [14]. The evolutionary tradeoffs exposed by experimental selection are experienced even in the absence of parasitoid infection. Blood cell number is constitutively higher in the evolved resistant strains, which presumably allows a faster and more robust defense against a wasp egg. However, the resistant larvae always suffer the cost when reared in competitive conditions. Because the costs arise from a constitutive investment in defense, regardless of whether parasitoids are present, these are sometimes referred to as “maintenance” costs or fixed costs [22]. In contrast, Bajgar et al. have measured a physiological “deployment” cost [22], which is conditionally experienced only once the host activates an immune response.It remains an open question the extent to which maintenance costs and deployment costs share mechanistic bases. In the present example, Bajgar et al. [14] show clearly that the machinery is in place to route energetic investment away from growth and development in favor of hemocyte proliferation. Extrapolating from the laboratory selection experiments [17–19], a natural increase in the epidemiological risk of parasitization in the wild might favor greater constitutive investment in hemocyte production. In such a scenario, it is easy to imagine the adaptive value of a mutation or genetic variant that results in higher expression of ENT2 in the lymph gland in the absence of infection, driving constitutively higher hemocyte number and protection against infection at the expense of constitutively lower nutrient storage and growth. In this way, a plastic switch could be converted into a hardwired trait, a deployment cost would become a maintenance cost, and a physiological tradeoff would become an evolutionary one. However, it is important to appreciate that there typically are many solutions to any biological problem, and constitutively elevated blood cell number could also evolve via mechanisms unrelated to adenosine signaling. A key challenge for life history biologists will be to bridge physiological studies such as that by Bajgar and colleagues [14] with the evolutionary studies that preceded it, testing whether physiological and evolutionary tradeoffs share a mechanistic basis.While in the bright light of day, evolutionary biologists can agree that the Darwinian Demon is just a ghost story, we have precious few examples of evolutionary or physiological tradeoffs where the mechanistic bases are well understood. More careful quantitative and genetic studies like that of Bajgar et al. [14] are necessary to carry us beyond reliance on abstract concepts like “resource pools” [2] and into mechanistic understanding of how life history tradeoffs operate on both the physiology of individuals and the evolution of species. 相似文献