Experimental evolution of a sexually selected display in yeast

The fundamental principle underlying sexual selection theory is that an allele conferring an advantage in the competition for mates will spread through a population. Remarkably, this has never been demonstrated empirically. We have developed an experimental system using yeast for testing genetic models of sexual selection. Yeast signal to potential partners by producing an attractive pheromone; stronger signallers are preferred as mates. We tested the effect of high and low levels of sexual selection on the evolution of a gene determining the strength of this signal. Under high sexual selection, an allele encoding a stronger signal was able to invade a population of weak signallers, and we observed a corresponding increase in the amount of pheromone produced. By contrast, the strong signalling allele failed to invade under low sexual selection. Our results demonstrate, for the first time, the spread of a sexually selected allele through a population, confirming the central assumption of sexual selection theory. Our yeast system is a powerful tool for investigating the genetics of sexual selection.     

The evolution of sexually selected traits and antagonistic androgen expression in actinopterygiian fishes

Many sexually selected traits in male fishes are controlled by testosterone. Directional selection for male ornaments could theoretically increase male testosterone levels over evolutionary timescales, and when genetically correlated, female testosterone levels as well. Because of the negative fitness consequences of high testosterone, it is plausible that female choice for sexually selected traits in males results in decreased female reproductive fitness. I used comparative analysis to examine the association between male peak testosterone expression and sexually selected ornaments. I also tested for genetic correlation between male and female androgen levels. The presence of sexually selected traits in males was significantly correlated with increased peak androgen levels in males as well as females, and female testosterone levels were significantly correlated with male peak testosterone titers, although the slope was only marginally <1. This suggests that selection to decouple high male and female testosterone levels is either weak or otherwise ineffective.     

The evolution of hybrid infertility: perpetual coevolution between gender-specific and sexually antagonistic genes

A new hypothesis is proposed for the rapid evolution of postzygotic reproductive isolation via hybrid infertility. The hypothesis is motivated by two lines of experimental research from Drosophila melanogaster that demonstrate that sexually antagonistic fitness variation is abundant and that epistatic fitness variation on the Y chromosome is common. The hypothesis states that the expression of sexually antagonistic genes leads to a gender-load in each sex. In response, gender-limited reproductive genes are selected to ameliorate, through pleiotropy, the expression of sexually antagonistic genes. Chronic coevolution between gender-limited genes and gender-unlimited sexually antagonistic genes causes rapid divergence of reproductive proteins among allopatric populations, ultimately leading to hybrid infertility.     

Detecting sexual conflict and sexually antagonistic coevolution

We begin by providing an operational definition of sexual conflict that applies to both inter- and intralocus conflict. Using this definition, we examine a series of simple coevolutionary models to elucidate fruitful approaches for detecting interlocus sexual conflict and resultant sexually antagonistic coevolution. We then use published empirical examples to illustrate the utility of these approaches. Three relevant attributes emerge. First, the dynamics of sexually antagonistic coevolution may obscure the conflict itself. Second, competing models of inter-sexual coevolution may yield similar population patterns near equilibria. Third, a variety of evolutionary forces underlying competing models may be acting simultaneously near equilibria. One main conclusion is that studies of emergent patterns in extant populations (e.g. studies of population and/or female fitness) are unlikely to allow us to distinguish among competing coevolutionary models. Instead, we need more research aimed at identifying the forces of selection acting on shared traits and sexually antagonistic traits. More specifically, we need a greater number of functional studies of female traits as well as studies of the consequences of both male and female traits for female fitness. A mix of selection and manipulative studies on these is likely the most promising route.     

Detecting sexually antagonistic coevolution with population crosses

The result of population crosses on traits such as mating rate, oviposition rate and survivorship are increasingly used to distinguish between modes of coevolution between the sexes. Two key hypotheses, erected from a verbal theory of sexually antagonistic coevolution, have been the subject of several recent tests. First, statistical interactions arising in population crosses are suggested to be indicative of a complex signal/receiver system. In the case of oviposition rates, an interaction between populations (x, y and z) would be indicated by the rank order of female oviposition rates achieved by x, y and z males changing depending upon the female (x, y or z) with which they mated. Second, under sexually antagonistic coevolution females will do 'best' when mated with their own males, where best is defined by the weakest response to the signal and the highest fitness. We test these hypotheses by crossing strains generated from a formal model of sexually antagonistic coevolution. Strains differ in the strength of natural selection acting on male and female traits. In our model, we assume sexually antagonistic coevolution of a single male signal and female receptor. The female receptor is treated as a preference function where both the slope and intercept of the function can evolve. Our results suggest that neither prediction is consistently supported. Interactions are not diagnostic of complex signal-receiver systems, and even under sexually antagonistic coevolution, females may do better mating with males of strains other than their own. These results suggest a reinterpretation of several recent experiments and have important implications for developing theories of speciation when sexually antagonistic coevolution is involved.     

Two-locus epistasis with sexually antagonistic selection: a genetic Parrondo's paradox

An example is provided where, with antagonistic selection and epistatic interaction of alleles at two loci, an autosomal allele can rise in frequency, persist in the population, and even continue to fixation, despite having an apparently lower average fitness than the alternative allele, in a process similar to Parrondo's paradox.     

Population genetics of sexually antagonistic mitochondrial mutants under inbreeding

In random mating populations, the fate of mitochondrial mutations with sexually antagonistic effects in males and females is based solely on their effects in females. Therefore, mitochondrial mutations that are beneficial for females but deleterious for males will be fixed in a deterministic model. Why then are males not less fertile? One among many several explanations is that inbreeding limits the ability of mutants to spread since the fitness of a mother is now linked to her son's fertility. We model this situation analytically and determine conditions under which such sexually antagonistic mitochondrial mutants can spread and fix in a population. We also provide alternative hypotheses for the lack of observed male sterility in natural populations.     

The effect of epistasis on sexually antagonistic genetic variation

There is increasing evidence of segregating sexually antagonistic (SA) genetic variation for fitness in laboratory and wild populations, yet the conditions for the maintenance of such variation can be restrictive. Epistatic interactions between genes can contribute to the maintenance of genetic variance in fitness and we suggest that epistasis between SA genes should be pervasive. Here, we explore its effect on SA genetic variation in fitness using a two locus model with negative epistasis. Our results demonstrate that epistasis often increases the parameter space showing polymorphism for SA loci. This is because selection in one locus is affected by allele frequencies at the other, which can act to balance net selection in males and females. Increased linkage between SA loci had more marginal effects. We also show that under some conditions, large portions of the parameter space evolve to a state where male benefit alleles are fixed at one locus and female benefit alleles at the other. This novel effect of epistasis on SA loci, which we term the ‘equity effect’, may have important effects on population differentiation and may contribute to speciation. More generally, these results support the suggestion that epistasis contributes to population divergence.     

Experimental evolution of a novel pathway for glycerol dissimilation inEscherichia coli

Wild-type Escherichia coli utilizes glycerol aerobically through an inducible pathway mediated by an ATP-dependent kinase and a glycerol 3-phosphate dehydrogenase which is a flavoprotein. A mutant, strain ECL424, employing a novel pathway for glycerol utilization was isolated. The novel pathway is mediated by an NAD-linked dehydrogenase and a dihydroxyacetone specific enzyme II of the phosphoenolpyruvate phosphotransferase system. This study describes the selection from strain ECL424, a derivative which grows more rapidly on glycerol. The derivative, strain ECL428, produces twice the parental levels of both the dehydrogenase and the enzyme II during growth on glycerol. The function of the dehydrogenase in wild-type cells is unknown, although hydroxyacetone (acetol), 3-hydroxy-2-butanone (acetoin), and 1-amino-2-propanone are gratuitous inducers. The induction can be prevented by glucose whose effect can be cancelled by external cyclic AMP. The effects of hydroxyacetone, glucose, and cyclic AMP are attenuated in the two mutants in which the dehydrogenase is produced at high basal levels. The dihydroxyacetone specific enzyme II is inducible by the substrate in both wild-type and mutant strains and serves for growth on the triose.     

The X chromosome is a hot spot for sexually antagonistic fitness variation

Sexually antagonistic alleles are selected discordantly between the sexes. Experimental evidence indicates that sexually antagonistic fitness variation is abundant in the genome of Drosophila melanogaster. Theory predicts that the X chromosome will be enriched with this type of variation. To test this prediction in D. melanogaster, we sampled, and cytogenetically cloned, 20 X chromosomes and compared their fitness variation to genome-wide levels. At the juvenile stage, in which gender roles are most similar, the X chromosome made no detectable contribution to genome-wide fitness variation. At the adult stage, in which gender roles diverge, the X chromosome was estimated to harbour 45% of the genome-wide fitness variation and 97% of the genome-wide sexually antagonistic variation. This genomic structure has important implications for the process of sexual selection because X-linked sexually antagonistic variation contributes to negative intersexual heritability for fitness, i.e. high-fitness males (females) produce, on average, low-fitness daughters (sons).     

Female choice of sexually antagonistic male adaptations: a critical review of some current research

We contrast some recent uses of the concept of male-female conflict, with the type of conflict that is inherent in traditional Darwinian female choice. Females in apparent conflict situations with males may suffer reduced lifetime reproduction, but nevertheless benefit because they obtain sons with superior manipulative abilities. Female defences against male manipulations may not be 'imperfect' because of inability to keep pace with male evolution, but in order to screen males and favour those that are especially good manipulators. We examine the consequences of these ideas, and of the difficulties of obtaining biologically realistic measures of female costs, for some recent theoretical and empirical presentations of male-female conflict ideas, and find that male-female conflict in the new sense is less certain than has been commonly supposed. Disentangling previous sexual selection ideas and the new conflict of interest models will probably often be difficult, because the two types of payoffs are not mutually exclusive.     

Decorin is a novel antagonistic ligand of the Met receptor

Decorin, a member of the small leucine-rich proteoglycan gene family, impedes tumor cell growth by down-regulating the epidermal growth factor receptor. Decorin has a complex binding repertoire, thus, we predicted that decorin would modulate the bioactivity of other tyrosine kinase receptors. We discovered that decorin binds directly and with high affinity (K_d = ∼1.5 nM) to Met, the receptor for hepatocyte growth factor (HGF). Binding of decorin to Met is efficiently displaced by HGF and less efficiently by internalin B, a bacterial Met ligand. Interaction of decorin with Met induces transient receptor activation, recruitment of the E3 ubiquitin ligase c-Cbl, and rapid intracellular degradation of Met (half-life = ∼6 min). Decorin suppresses intracellular levels of β-catenin, a known downstream Met effector, and inhibits Met-mediated cell migration and growth. Thus, by antagonistically targeting multiple tyrosine kinase receptors, decorin contributes to reduction in primary tumor growth and metastastic spreading.     

Intralocus sexual conflict for fitness: sexually antagonistic alleles for testosterone

Intralocus sexual conflict occurs when a trait encoded by the same genetic locus in the two sexes has different optima in males and females. Such conflict is widespread across taxa, however, the shared phenotypic traits that mediate the conflict are largely unknown. We examined whether the sex hormone, testosterone (T), that controls sexual differentiation, contributes to sexually antagonistic fitness variation in the bank vole, Myodes glareolus. We compared (opposite-sex) sibling reproductive fitness in the bank vole after creating divergent selection lines for T. This study shows that selection for T was differentially associated with son versus daughter reproductive success, causing a negative correlation in fitness between full siblings. Our results demonstrate the presence of intralocus sexual conflict for fitness in this small mammal and that sexually antagonistic selection is acting on T. We also found a negative correlation in fitness between parents and their opposite-sex progeny (e.g. father-daughter), highlighting a dilemma for females, as the indirect genetic benefits of selecting reproductively successful males (high T) are lost with daughters. We discuss mechanisms that may mitigate this disparity between progeny quality.     

Intra-locus sexual conflict and sexually antagonistic genetic variation in hermaphroditic animals

Intra-locus sexual conflict results when sex-specific selection pressures for a given trait act against the intra-sexual genetic correlation for that trait. It has been found in a wide variety of taxa in both laboratory and natural populations, but the importance of intra-locus sexual conflict and sexually antagonistic genetic variation in hermaphroditic organisms has rarely been considered. This is not so surprising given the conceptual and theoretical association of intra-locus sexual conflict with sexual dimorphism, but there is no a priori reason why intra-locus sexual conflict cannot occur in hermaphroditic organisms as well. Here, I discuss the potential for intra-locus sexual conflict in hermaphroditic animals and review the available evidence for such conflict, and for the existence of sexually antagonistic genetic variation in hermaphrodites. I argue that mutations with asymmetric effects are particularly likely to be important in mediating sexual antagonism in hermaphroditic organisms. Moreover, sexually antagonistic genetic variation is likely to play an important role in inter-individual variation in sex allocation and in transitions to and from gonochorism (separate sexes) in simultaneous hermaphrodites. I also describe how sequential hermaphrodites may experience a unique form of intra-locus sexual conflict via antagonistic pleiotropy. Finally, I conclude with some suggestions for further research.     

Characterization of a novel non-constitutive photomorphogenic cop1 allele

A specific light program consisting of multiple treatments with alternating red and far-red light pulses was used to isolate mutants in phytochrome A-dependent signal transduction in Arabidopsis seedlings. Because of their phenotype, the mutants were called eid (empfindlicher im dunkelroten Licht, which means hypersensitive in far-red light). One of the isolated mutants, eid6, is a novel recessive allele of the COP1 gene (constitutive photomorphogenic 1) that carries an amino acid transition in a conserved histidine residue of the RING finger domain. Mutant seedlings exhibited an extreme hypersensitivity towards all tested light qualities, but in contrast to known cop1 alleles, no constitutive photomorphogenic phenotype was detectable in darkness. Thus, the novel cop1eid6 allele seems to encode for a protein whose remaining activity is sufficient for the suppression of photomorphogenesis in dark-grown plants. In adult cop1eid6 plants, the development of the Cop1 phenotype is dominated by phytochrome B. Comparison of the phenotype of the novel cop1eid6 and the weak cop1-4 allele under continuous far-red light indicates that the RING finger and coiled-coil domains of COP1 are sufficient for some specific regulatory function in phytochrome A-dependent high irradiance responses.     

Identification and characterization of a novel mouse prion gene allele

The major determinant of prion disease incubation time in mice is thought to be the amino acid sequence of the prion protein. Two alleles of the mouse prion gene (Prnp) have been described, where Prnp^a (Leu-108, Thr-189) and Prnp^b (Phe-108, Val-189) are associated with short and long incubation times, to defined prion strains, respectively. As part of a survey of inbred mouse lines, the prion gene open reading frame was sequenced and revealed a new allele, Prnp^c (Phe-108, Thr-189), in the strain MAI/Pas. To study the influence of Prnp^c independently of the MAI/Pas genetic background, we generated a congenic line in which Prnp^c was bred onto the C57BL/6JOlaHsd background. Following intracerebral inoculation with Chandler/RML scrapie prions, the congenic mice showed an increased mean incubation time relative to C57BL/6JOlaHsd, of over 100 days. However, no differences were observed in the intensity and pattern of PrP immunoreactivity deposition or spongiosis. We conclude that the new allele, Prnp^c, modulates incubation time but not neuropathology and that the previous classification of mice into two distinct groups based on incubation time and Prnp genotype should now be revised.     

The effect of purging on sexually selected traits through antagonistic pleiotropy with survival

Sexually selected traits are expected to evolve to a point where their positive effect on reproductive success is counterbalanced by their negative effect on survival. At the genetic level, such a trade-off implies antagonistic pleiotropy between survival and the expression of sexually selected traits. Yet, the consequences of such a genetic architecture have been largely overlooked in studies examining how inbreeding influences sexually selected traits. These studies have solely interpreted their results as an effect of increased homozygosity. An alternative, however, is that purging of recessive alleles deleterious for survival when inbreeding increases can negatively affect the expression of sexually selected traits through antagonistic pleiotropy. We tested this hypothesis by analyzing the effects of inbreeding on several male ornaments and life-history traits across 20 captive populations of guppies (Poecilia reticulata) with varying levels of inbreeding. Only one ornament, orange area, decreased in its expression with an increasing level of inbreeding. This was most likely due to purging because we found no within-population relationship between orange area and the inbreeding coefficient. We further tested this hypothesis by crossing unrelated individuals from the four most inbred populations, creating a group of individuals with purged genomes but restored heterozygosity. Restoration of heterozygosity only slightly increased orange area, confirming that the decrease in orange area in the inbred populations most likely resulted from purging. These results support previous studies suggesting the existence of antagonistic pleiotropy between ornament expression and survival.     

Sisters' curse: sexually antagonistic effects constrain the spread of a mitochondrial haplogroup superior in sperm competition

Maternal inheritance of mitochondria creates a sex-specific selective sieve with implications for male longevity, disease susceptibility and infertility. Because males are an evolutionary dead end for mitochondria, mitochondrial mutations that are harmful or beneficial to males but not females cannot respond directly to selection. Although the importance of this male/female asymmetry in evolutionary response depends on the extent to which mitochondrial mutations exert antagonistic effects on male and female fitness, few studies have documented sex-specific selection acting on mitochondria. Here, we exploited the discovery of two highly divergent mitochondrial haplogroups (A and B2) in central Panamanian populations of the pseudoscorpion Cordylochernes scorpioides. Next-generation sequencing and phylogenetic analyses suggest that selection on the ND4 and ND4L mitochondrial genes may partially explain sexually antagonistic mitochondrial effects on reproduction. Males carrying the rare B2 mitochondrial haplogroup enjoy a marked advantage in sperm competition, but B2 females are significantly less sexually receptive at second mating than A females. This reduced propensity for polyandry is likely to significantly reduce female lifetime reproductive success, thereby limiting the spread of the male beneficial B2 haplogroup. Our findings suggest that maternal inheritance of mitochondria and sexually antagonistic selection can constrain male adaptation and sexual selection in nature.