MHC studies in nonmodel vertebrates: what have we learned about natural selection in 15 years?

Elucidating how natural selection promotes local adaptation in interaction with migration, genetic drift and mutation is a central aim of evolutionary biology. While several conceptual and practical limitations are still restraining our ability to study these processes at the DNA level, genes of the major histocompatibility complex (MHC) offer several assets that make them unique candidates for this purpose. Yet, it is unclear what general conclusions can be drawn after 15 years of empirical research that documented MHC diversity in the wild. The general objective of this review is to complement earlier literature syntheses on this topic by focusing on MHC studies other than humans and mice. This review first revealed a strong taxonomic bias, whereby many more studies of MHC diversity in natural populations have dealt with mammals than all other vertebrate classes combined. Secondly, it confirmed that positive selection has a determinant role in shaping patterns of nucleotide diversity in MHC genes in all vertebrates studied. Yet, future tests of positive selection would greatly benefit from making better use of the increasing number of models potentially offering more statistical rigour and higher resolution in detecting the effect and form of selection. Thirdly, studies that compared patterns of MHC diversity within and among natural populations with neutral expectations have reported higher population differentiation at MHC than expected either under neutrality or simple models of balancing selection. Fourthly, several studies showed that MHC-dependent mate preference and kin recognition may provide selective factors maintaining polymorphism in wild outbred populations. However, they also showed that such reproductive mechanisms are complex and context-based. Fifthly, several studies provided evidence that MHC may significantly influence fitness, either by affecting reproductive success or progeny survival to pathogens infections. Overall, the evidence is compelling that the MHC currently represents the best system available in vertebrates to investigate how natural selection can promote local adaptation at the gene level despite the counteracting actions of migration and genetic drift. We conclude this review by proposing several directions where future research is needed.     

Humans act against the natural process of breeder selection: A modern sickness for animal populations?

We present a new idea about the possible effects of human-induced mortality on different age cohorts (i.e., breeders vs. juveniles) in long-lived animals. Our hypothesis is based on Curios idea on the effect of natural selective processes on cohorts to explain age-related increases in fecundity (selection hypothesis). We believe that negative human pressure may modify such contribution to reproduction of good versus low quality phenotypes, altering the genetic structure of the population. Ecologists and environmental managers in general should be aware of how stochastic events provoked by humans may induce changes in the genetic structure of populations.     

Phenotypic shifts caused by predation: selection or life-history shifts?

Predators can impose both selection and life-history shifts in prey populations. Because both processes may affect phenotypic distributions, the estimates of selection differentials may be biased. We carried out two field experiments to disentangle these separate effects. We studied whether dragonfly predation by Aeshna cyanea changes the distributions in body size and lamellae morphology in the damselfly Lestes sponsa. Damselflies have caudal lamellae which are used in escapes by swimming. In a first experiment, we manipulated predator presence (No Aeshna, Encaged Aeshna or Free-ranging Aeshna) and stopped the experiment when all larvae had moulted once. In a second experiment, larvae were confronted with a Free-ranging Aeshna but collected before moulting, and survivors were compared with a control sample taken at the start of the experiment. The presence of Aeshna largely reduced the survival probabilities of the Lestes larvae at a very similar rate in both experiments. Daily survival probabilities did not differ between the No Aeshna and Encaged Aeshna treatments. In the Free-ranging Aeshna treatment of the first experiment, size was reduced compared to the other two treatments, creating a significant apparent selection differential. This was probably mainly due to predator-induced reduced growth because in the second experiment, where growth effects were excluded, size of the survivors did not differ from the control sample. In both experiments there was a significant selection pressure for larger lamellae. Standardized directional selection differentials were similar in both experiments (0.57 and 0.28 phenotypic standard deviation units). No survival selection on lamellae shape was detected. These results are in agreement with previous findings that lamellae size, but not lamellae shape, enhances swimming performance and thereby predator escape in this species. This revised version was published online in July 2006 with corrections to the Cover Date.     

How strong is natural selection?

The strength of selection in nature has long been a controversial subject, partly because there were few quantitative measurements of phenotypic selection available until recently. In a new paper, Kingsolver and colleagues reviewed 63 studies and found that the median standardized directional selection gradient (a measure of the strength of phenotypic selection) was 0.16. Whether this means selection in nature is strong or weak depends both on one's point of view and on the error in selection estimates.     

What can natural selection explain?

One approach to assess the explanatory power of natural selection is to ask what type of facts it can explain. The standard list of explananda includes facts like trait frequencies or the survival of particular organisms. Here, I argue that this list is incomplete: natural selection can also explain a specific kind of individual-level fact that involves traits. The ability of selection to explain this sort of fact (‘trait facts’) vindicates the explanatory commitments of empirical studies on microevolution. Trait facts must be distinguished from a closely related kind of fact, that is, the fact that a particular individual x has one trait rather than another. Whether or not selection can explain the latter type of fact is highly controversial. According to the so-called ‘Negative View’ it cannot be explained by selection. I defend the Negative View against Nanay’s (2005) objection.     

Sexual dimorphism in snake tail length: sexual selection,natural selection,or morphological constraint?

Male snakes typically have longer tails relative to body length than females, but the extent of this dimorphism varies among species. Three hypotheses have been suggested to explain tail dimorphism. The Morphological Constraint Hypothesis proposes that males have relatively longer tails to accommodate hemipenes and retractor muscles. The Female Reproductive Output Hypothesis proposes that females have relatively shorter tails as a secondary result of natural selection for increased reproductive capacity. The Male Mating Ability Hypothesis proposes that sexual selection favours relatively longer tails in males during courtship. These hypotheses make different predictions about the relationships among tail length, body size, male reproductive morphology, female reproductive output, mode of reproduction, and male mating behaviour among and within taxa. Predictions were tested using published data for 56 genera in the family Colubridae and original data for the water snake, Nerodia sipedon. Tail length dimorphism was more male-biased in tam having relatively short tails (r=–0.52, P < 0.001), hemipenes and retractor muscles occupied a greater proportion of the tail in taxa having relatively short tails (r=– 0.71, P < 0.00l and r=– 0.66, P = 0.001, respectively), and tail length dimorphism was more male-biased in taxa in which body size dimorphism was more female-biased (r=– 0.60, P < 0.001). These results support both the Morphological Constraint Hypotheses and the Female Reproductive Output Hypothesis. However, tests of other predictions, including those regarding patterns within N. sipedon , failed to support any of the three hypotheses. Comparisons among taxa suggest several species in which further tests of these hypotheses would be especially appropriate.     

To what extent do microsatellite markers reflect genome‐wide genetic diversity in natural populations?

Microsatellite variability is widely used to infer levels of genetic diversity in natural populations. However, the ascertainment bias caused by typically selecting only the most polymorphic markers in the genome may lead to reduced sensitivity for judging genome-wide levels of genetic diversity. To test this potential limitation of microsatellite-based approaches, we assessed the degree of nucleotide diversity in noncoding regions of eight different carnivore populations, including inbred as well as outbred populations, by sequencing 10 introns (5.4–5.7 kb) in 20 individuals of each population (wolves, coyotes, wolverines and lynxes). Estimates of nucleotide diversity varied 30-fold (7.1 × 10⁻⁵ –2.1 × 10⁻³), with densities of one single nucleotide polymorphism every 112–5446 bp. Microsatellite genotyping (10–27 markers) of the same animals revealed mean multilocus heterozygosities of 0.54–0.78, a 1.4-fold difference among populations. There was a positive yet not perfect ( r ²  = 0.70) correlation between microsatellite marker heterozygosity and nucleotide diversity at the population level. For example, point estimates of nucleotide diversity varied in some cases with an order of magnitude despite very similar levels of microsatellite marker heterozygosity. Moreover, at the individual level, no significant correlation was found. Our results imply that variability at microsatellite marker sets typically used in population studies may not accurately reflect the underlying genomic diversity. This suggests that researchers should consider using resequencing-based approaches for assessing genetic diversity when accurate inference is critical, as in many conservation and management contexts.     

Is there really natural selection affecting the l frequencies (long hair) in the Brazilian cat populations?

The scientific literature on cat genetics contains a presumed typical example of natural selection affecting l frequencies (long hair) in 16 Brazilian cat populations. It has been observed that the hotter and more tropical the climate in Brazil, the lower the values of l frequencies in the cat populations. Nevertheless, this study of some new cat populations in Latin America showed that all of them, independent of the climate, had high or very high l frequencies. l postulate that an alternative migrational-historical hypothesis exists that explains the correlation between the l frequencies and climate characteristics (which are correlated with the latitude) without using natural selection explanations concerning the appearance of the l allele in Brazil.     

Phenotypic selection on floral scent: trade-off between attraction and deterrence?

Flowers emit a large variety of floral signals that play a fundamental role in the communication of plants with their mutualists and antagonists. We investigated phenotypic selection on floral scent and floral display using the rewarding orchid species Gymnadenia odoratissima. We found positive directional selection on inflorescence size, as well as positive and negative selection on floral scent compounds. Structural equation modeling showed that “active” compounds, i.e. those that were shown in earlier investigations to be detected by pollinator insects, were positively linked to fitness, whereas “non-active” were negatively linked to fitness. Our results suggest that different patterns of selection impact on different scent compounds, which may relate to the functions of compounds for attracting/deterring insects.     

Does genetic diversity limit disease spread in natural host populations?

It is a commonly held view that genetically homogenous host populations are more vulnerable to infection than genetically diverse populations. The underlying idea, known as the 'monoculture effect,' is well documented in agricultural studies. Low genetic diversity in the wild can result from bottlenecks (that is, founder effects), biparental inbreeding or self-fertilization, any of which might increase the risk of epidemics. Host genetic diversity could buffer populations against epidemics in nature, but it is not clear how much diversity is required to prevent disease spread. Recent theoretical and empirical studies, particularly in Daphnia populations, have helped to establish that genetic diversity can reduce parasite transmission. Here, we review the present theoretical work and empirical evidence, and we suggest a new focus on finding 'diversity thresholds.'     

Experimental studies of group selection: what do they tell us about group selection in nature?

The study of group selection has developed along two autonomous lines. One approach, which we refer to as the adaptationist school, seeks to understand the evolution of existing traits by examining plausible mechanisms for their evolution and persistence. The other approach, which we refer to as the genetic school, seeks to examine how currently acting artificial or natural selection changes traits within populations and focuses on current evolutionary change. The levels of selection debate lies mainly within the adaptationist school, whereas the experimental studies of group selection lie within the genetic school. Because of the very different traditions and goals of these two schools, the experimental studies of group selection have not had a major impact on the group selection debate. We review the experimental results of the genetic school in the context of the group selection controversy and address the following questions: Under what conditions is group selection effective? What is the genetic basis of a response to group selection? How common is group selection in nature?     

Frequency‐dependent selection: a diversifying force in microbial populations

The benefits of “bet‐hedging” strategies have been assumed to be the main cause of phenotypic diversity in biological populations. However, in their recent work, Healey et al ( 2016 ) provide experimental support for negative frequency‐dependent selection (NFDS) as an alternative driving force of diversity. NFDS favors rare phenotypes over common ones, resulting in an evolutionarily stable mixture of phenotypes that is not necessarily optimal for population growth.     

Interfamily variation in amphibian early life-history traits: raw material for natural selection?

The embryonic development and time to hatching of eggs can be highly adaptive in some species, and thus under selective pressure. In this study, we examined the underlying interfamily variation in hatching timing and embryonic development in a population of an oviparous amphibian, the rough-skinned newt (Taricha granulosa). We found significant, high variability in degree of embryonic development and hatching timing among eggs from different females. Patterns of variation were present regardless of temperature. We also could not explain the differences among families by morphological traits of the females or their eggs. This study suggests that the variation necessary for natural selection to act upon is present in the early life history of this amphibian.     

Phenotypic screening meets natural products in drug discovery†

The Nobel Prize in Physiology or Medicine 2015 was awarded for discoveries related to the control of parasitic diseases using natural products of microbial and plant origin. In current drug discovery programs, synthesized compounds are widely used as a screening source; however, this award reminds us of the importance of natural products. Here, we introduce our phenotypic screening methods based on changes in cell morphology and discuss their effectiveness and impact for natural products in drug discovery.     

What was Fisher's fundamental theorem of natural selection and what was it for?

Fisher's 'fundamental theorem of natural selection' is notoriously abstract, and, no less notoriously, many take it to be false. In this paper, I explicate the theorem, examine the role that it played in Fisher's general project for biology, and analyze why it was so very fundamental for Fisher. I defend and Lessard (1997) in the view that the theorem is in fact a true theorem if, as Fisher claimed, 'the terms employed' are 'used strictly as defined' (1930, p. 38). Finally, I explain the role that projects such as Fisher's play in the progress of scientific inquiry.     

Disruptive selection and then what?

Disruptive selection occurs when extreme phenotypes have a fitness advantage over more intermediate phenotypes. The phenomenon is particularly interesting when selection keeps a population in a disruptive regime. This can lead to increased phenotypic variation while disruptive selection itself is diminished or eliminated. Here, we review processes that increase phenotypic variation in response to disruptive selection and discuss some of the possible outcomes, such as sympatric species pairs, sexual dimorphisms, phenotypic plasticity and altered community assemblages. We also identify factors influencing the likelihoods of these different outcomes.