Susan E. Johnston

Life history trade-offs at a single locus maintain sexually selected genetic variation

Sexual selection, through intra-male competition or female choice, is assumed to be a source of strong and sustained directional selection in the wild. In the presence of such strong directional selection, alleles enhancing a particular trait are predicted to become fixed within a population, leading to a decrease in the underlying genetic variation. However, there is often considerable genetic variation underlying sexually selected traits in wild populations, and consequently, this phenomenon has become a long-discussed issue in the field of evolutionary biology. In wild Soay sheep, large horns confer an advantage in strong intra-sexual competition, yet males show an inherited polymorphism for horn type and have substantial genetic variation in their horn size. Here we show that most genetic variation in this trait is maintained by a trade-off between natural and sexual selection at a single gene, relaxin-like receptor 2 (RXFP2). We found that an allele conferring larger horns, Ho+, is associated with higher reproductive success, whereas a smaller horn allele, HoP, confers increased survival, resulting in a net effect of overdominance (that is, heterozygote advantage) for fitness at RXFP2. The nature of this trade-off is simple relative to commonly proposed explanations for the maintenance of sexually selected traits, such as genic capture (‘good genes’) and sexually antagonistic selection. Our results demonstrate that by identifying the genetic architecture of trait variation, we can determine the principal mechanisms maintaining genetic variation in traits under strong selection and explain apparently counter-evolutionary observations.

Sex-dependent dominance at a single locus maintains variation in age at maturity in salmon

Males and females share many traits that have a common genetic basis; however, selection on these traits often differs between the sexes, leading to sexual conflict. Under such sexual antagonism, theory predicts the evolution of genetic architectures that resolve this sexual conflict. Yet, despite intense theoretical and empirical interest, the specific loci underlying sexually antagonistic phenotypes have rarely been identified, limiting our understanding of how sexual conflict impacts genome evolution and the maintenance of genetic diversity. Here we identify a large effect locus controlling age at maturity in Atlantic salmon (Salmo salar), an important fitness trait in which selection favours earlier maturation in males than females, and show it is a clear example of sex-dependent dominance that reduces intralocus sexual conflict and maintains adaptive variation in wild populations. Using high-density single nucleotide polymorphism data across 57 wild populations and whole genome re-sequencing, we find that the vestigial-like family member 3 gene (VGLL3) exhibits sex-dependent dominance in salmon, promoting earlier and later maturation in males and females, respectively. VGLL3, an adiposity regulator associated with size and age at maturity in humans, explained 39% of phenotypic variation, an unexpectedly large proportion for what is usually considered a highly polygenic trait. Such large effects are predicted under balancing selection from either sexually antagonistic or spatially varying selection. Our results provide the first empirical example of dominance reversal allowing greater optimization of phenotypes within each sex, contributing to the resolution of sexual conflict in a major and widespread evolutionary trade-off between age and size at maturity. They also provide key empirical evidence for how variation in reproductive strategies can be maintained over large geographical scales. We anticipate these findings will have a substantial impact on population management in a range of harvested species where trends towards earlier maturation have been observed.

Genome-wide association mapping identifies the genetic basis of discrete and quantitative variation in sexual weaponry in a wild sheep population

Understanding the genetic architecture of phenotypic variation in natural populations is a fundamental goal of evolutionary genetics. Wild Soay sheep (Ovis aries) have an inherited polymorphism for horn morphology in both sexes, controlled by a single autosomal locus, Horns. The majority of males have large normal horns, but a small number have vestigial, deformed horns, known as scurs; females have either normal horns, scurs or no horns (polled). Given that scurred males and polled females have reduced fitness within each sex, it is counterintuitive that the polymorphism persists within the population. Therefore, identifying the genetic basis of horn type will provide a vital foundation for understanding why the different morphs are maintained in the face of natural selection. We conducted a genome‐wide association study using ∼36 000 single nucleotide polymorphisms (SNPs) and determined the main candidate for Horns as RXFP2, an autosomal gene with a known involvement in determining primary sex characters in humans and mice. Evidence from additional SNPs in and around RXFP2 supports a new model of horn‐type inheritance in Soay sheep, and for the first time, sheep with the same horn phenotype but different underlying genotypes can be identified. In addition, RXFP2 was shown to be an additive quantitative trait locus (QTL) for horn size in normal‐horned males, accounting for up to 76% of additive genetic variation in this trait. This finding contrasts markedly from genome‐wide association studies of quantitative traits in humans and some model species, where it is often observed that mapped loci only explain a modest proportion of the overall genetic variation.

Genome mapping in intensively studied wild vertebrate populations

Over the past decade, long-term studies of vertebrate populations have been the focus of many quantitative genetic studies. As a result, we have a clearer understanding of why some fitness-related traits are heritable and under selection, but are apparently not evolving. An exciting extension of this work is to identify the genes underlying phenotypic variation in natural populations. The advent of next-generation sequencing and high-throughput single nucleotide polymorphism (SNP) genotyping platforms means that mapping studies are set to become widespread in those wild populations for whom appropriate phenotypic data and DNA samples are available. Here, we highlight the progress made in this area and define evolutionary genetic questions that have become tractable with the arrival of these new genomics technologies.

Molecular evolutionary and population genomic analysis of the nine-spined stickleback using a modified restriction-site-associated DNA tag approach

In recent years, the explosion of affordable next generation sequencing technology has provided an unprecedented opportunity to conduct genome‐wide studies of adaptive evolution in organisms previously lacking extensive genomic resources. Here, we characterize genome‐wide patterns of variability and differentiation using pooled DNA from eight populations of the nine‐spined stickleback (Pungitius pungitius L.) from marine, lake and pond environments. We developed a novel genome complexity reduction protocol, defined as paired‐end double restriction‐site‐associated DNA (PE dRAD), to maximize read coverage at sequenced locations. This allowed us to identify over 114 000 short consensus sequences and 15 000 SNPs throughout the genome. A total of 6834 SNPs mapped to a single position on the related three‐spined stickleback genome, allowing the detection of genomic regions affected by divergent and balancing selection, both between species and between freshwater and marine populations of the nine‐spined stickleback. Gene ontology analysis revealed 15 genomic regions with elevated diversity, enriched for genes involved in functions including immunity, chemical stimulus response, lipid metabolism and signalling pathways. Comparisons of marine and freshwater populations identified nine regions with elevated differentiation related to kidney development, immunity and MAP kinase pathways. In addition, our analysis revealed that a large proportion of the identified SNPs mapping to LG XII is likely to represent alternative alleles from divergent X and Y chromosomes, rather than true autosomal markers following Mendelian segregation. Our work demonstrates how population‐wide sequencing and combining inter‐ and intra‐specific RAD analysis can uncover genome‐wide patterns of differentiation and adaptations in a non‐model species.

Genome-wide SNP analysis reveals a genetic basis for sea-age variation in a wild population of Atlantic salmon (Salmo salar).

Delaying sexual maturation can lead to larger body size and higher reproductive success, but carries an increased risk of death before reproducing. Classical life history theory predicts that trade‐offs between reproductive success and survival should lead to the evolution of an optimal strategy in a given population. However, variation in mating strategies generally persists, and in general, there remains a poor understanding of genetic and physiological mechanisms underlying this variation. One extreme case of this is in the Atlantic salmon (Salmo salar), which can show variation in the age at which they return from their marine migration to spawn (i.e. their ‘sea age’). This results in large size differences between strategies, with direct implications for individual fitness. Here, we used an Illumina Infinium SNP array to identify regions of the genome associated with variation in sea age in a large population of Atlantic salmon in Northern Europe, implementing individual‐based genome‐wide association studies (GWAS) and population‐based FST outlier analyses. We identified several regions of the genome which vary in association with phenotype and/or selection between sea ages, with nearby genes having functions related to muscle development, metabolism, immune response and mate choice. In addition, we found that individuals of different sea ages belong to different, yet sympatric populations in this system, indicating that reproductive isolation may be driven by divergence between stable strategies. Overall, this study demonstrates how genome‐wide methodologies can be integrated with samples collected from wild, structured populations to understand their ecology and evolution in a natural context.

Horn type and horn length genes map to the same chromosomal region in Soay sheep.

The evolution of male weaponry in animals is driven by sexual selection, which is predicted to reduce the genetic variability underlying such traits. Soay sheep have an inherited polymorphism for horn type in both sexes, with males presenting with either large, normal horns or small, deformed horns (scurs). In addition, there is additive genetic variation in horn length among males with normal horns. Given that scurred males cannot win conflicts with normal-horned males, it is unusual that genes conferring scurs should persist in the population. Identifying the genetic basis of these traits should help us in understanding their evolution. We developed microsatellite markers in a targeted region of the Soay sheep genome and refined the location of the Horns locus (Ho) to a ∼7.4 cM interval on chromosome 10 (LOD=8.78). We then located quantitative trait loci spanning a 34 cM interval with a peak centred close to Ho, which explained the majority of the genetic variation for horn length and base circumference in normal-horned males (LOD=2.51 and LOD=1.04, respectively). Therefore, the genetic variation in both horn type and horn length is attributable to the same chromosomal region. Understanding the maintenance of horn type and length variation will require an investigation of selection on genotypes that (co)determine both traits.

Conserved Genetic Architecture Underlying Individual Recombination Rate Variation in a Wild Population of Soay sheep (Ovis aries)

Meiotic recombination breaks down linkage disequilibrium (LD) and forms new haplotypes, meaning that it is an important driver of diversity in eukaryotic genomes. Understanding the causes of variation in recombination rate is important in interpreting and predicting evolutionary phenomena and in understanding the potential of a population to respond to selection. However, despite attention in model systems, there remains little data on how recombination rate varies at the individual level in natural populations. Here we used extensive pedigree and high-density SNP information in a wild population of Soay sheep (Ovis aries) to investigate the genetic architecture of individual autosomal recombination rates. Individual rates were high relative to other mammal systems and were higher in males than in females (autosomal map lengths of 3748 and 2860 cM, respectively). The heritability of autosomal recombination rate was low but significant in both sexes (h2 = 0.16 and 0.12 in females and males, respectively). In females, 46.7% of the heritable variation was explained by a subtelomeric region on chromosome 6; a genome-wide association study showed the strongest associations at locus RNF212, with further associations observed at a nearby ∼374-kb region of complete LD containing three additional candidate loci, CPLX1, GAK, and PCGF3. A second region on chromosome 7 containing REC8 and RNF212B explained 26.2% of the heritable variation in recombination rate in both sexes. Comparative analyses with 40 other sheep breeds showed that haplotypes associated with recombination rates are both old and globally distributed. Both regions have been implicated in rate variation in mice, cattle, and humans, suggesting a common genetic architecture of recombination rate variation in mammals.

Butterfly speciation and the distribution of gene effect sizes fixed during adaptation

Mimicry has had a significant historical influence as a tractable system for studying adaptation and is known to play a role in speciation. Here, we discuss recent theoretical treatment of adaptive walks to local adaptive peaks and contrast this with the adaptive landscape of mimicry. Evolution of novel Müllerian mimicry patterns almost certainly involves substitution of a major mutation to provide an initial similarity to the model, such that major gene effects are expected to an even greater degree than for other adaptive traits. The likelihood of large adaptive peak shifts in mimicry evolution may therefore promote speciation. In addition, mimicry adaptive peaks are determined by the local abundance of particular patterns and may be more fluid than the case for other traits. It will therefore be of considerable interest to test empirically the distribution of effect sizes fixed during mimicry evolution. Here, we show the feasibility of this by presenting a preliminary quantitative trait locus (QTL) analysis of Heliconius colour patterns. This shows that a number of modifier loci of different effect sizes influence forewing band morphology. We also show multiple pleiotropic effects of major Heliconius patterning loci and discuss the likelihood of multiple substitutions at the same loci in pattern evolution, which would inflate the importance of major loci in QTL analysis of the gene effect sizes. Analyses such as these have the potential to uncover the genetic architecture of both within and between species adaptive differences.

Evolutionary mysteries in meiosis

Meiosis is a key event of sexual life cycles in eukaryotes. Its mechanistic details have been uncovered in several model organisms, and most of its essential features have received various and often contradictory evolutionary interpretations. In this perspective, we present an overview of these often ‘weird’ features. We discuss the origin of meiosis (origin of ploidy reduction and recombination, two-step meiosis), its secondary modifications (in polyploids or asexuals, inverted meiosis), its importance in punctuating life cycles (meiotic arrests, epigenetic resetting, meiotic asymmetry, meiotic fairness) and features associated with recombination (disjunction constraints, heterochiasmy, crossover interference and hotspots). We present the various evolutionary scenarios and selective pressures that have been proposed to account for these features, and we highlight that their evolutionary significance often remains largely mysterious. Resolving these mysteries will likely provide decisive steps towards understanding why sex and recombination are found in the majority of eukaryotes. This article is part of the themed issue ‘Weird sex: the underappreciated diversity of sexual reproduction’.