Explore the vast range of titles available.

Recombination, the exchange of DNA between maternal and paternal chromosomes during meiosis, is an essential feature of sexual reproduction in nearly all multicellular organisms. While the role of recombination in the evolution of sex has received theoretical and empirical attention, less is known about how recombination rate itself evolves and what influence this has on evolutionary processes within sexually reproducing organisms. Here, we explore the patterns of, and processes governing recombination in eukaryotes. We summarize patterns of variation, integrating current knowledge with an analysis of linkage map data in 353 organisms. We then discuss proximate and ultimate processes governing recombination rate variation and consider how these influence evolutionary processes. Genome-wide recombination rates (cM/Mb) can vary more than tenfold across eukaryotes, and there is large variation in the distribution of recombination events across closely related taxa, populations and individuals. We discuss how variation in rate and distribution relates to genome architecture, genetic and epigenetic mechanisms, sex, environmental perturbations and variable selective pressures. There has been great progress in determining the molecular mechanisms governing recombination, and with the continued development of new modelling and empirical approaches, there is now also great opportunity to further our understanding of how and why recombination rate varies. This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.

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’.

Meiotic recombination through chromosomal crossovers ensures proper segregation of homologous chromosomes during meiosis, while also breaking down linkage disequilibrium and shuffling alleles at loci located on the same chromosome. Rates of recombination can vary between species, but also between and within individuals, sex and chromosomes within species. Indeed, the Atlantic salmon genome is known to have clear sex differences in recombination with female biased heterochiasmy and markedly different landscapes of crossovers between males and females. In male meiosis, crossovers occur strictly in the telomeric regions, whereas in female meiosis crossovers tend to occur closer to the centromeres. However, little is known about the genetic control of these patterns and how this differs at the individual level. Here, we investigate genetic variation in individual measures of recombination in > 5000 large full-sib families of a Norwegian Atlantic salmon breeding population with high-density SNP genotypes. We show that females had 1.6 × higher crossover counts (CC) than males, with autosomal linkage maps spanning a total of 2174 cM in females and 1483 cM in males. However, because of the extreme telomeric bias of male crossovers, female recombination is much more important for generation of new haplotypes with 8 × higher intra-chromosomal genetic shuffling than males. CC was heritable in females (h 2  = 0.11) and males (h 2  = 0.10), and shuffling was also heritable in both sex but with a lower heritability in females (h 2  = 0.06) than in males (h 2  = 0.11). Inter-sex genetic correlations for both traits were close to zero, suggesting that rates and distribution of crossovers are genetically distinct traits in males and females, and that there is a potential for independent genetic change in both sexes in the Atlantic Salmon. Together, these findings give novel insights into the genetic architecture of recombination in salmonids and contribute to a better understanding of how rates and distribution of recombination may evolve in eukaryotes more broadly.

Meiotic crossover patterning shows huge variation within and between chromosomes, individuals, and species, yet the molecular and evolutionary causes and consequences of this variation remain poorly understood. A key step is to understand the genetic architecture of the crossover rate, positioning, and interference to determine if these factors are governed by common or distinct genetic processes. Here, we investigate individual variation in autosomal crossover count, crossover position (measured as both intra-chromosomal shuffling and distance to telomere), and crossover interference in a large breeding population of domestic pigs ( N  = 82,474 gametes). We show that all traits are heritable in females at the gamete (h 2  = 0.07–0.11) and individual mean levels (h 2  = 0.08–0.41). In females, crossover count, and interference are strongly associated with RNF212 , but crossover positioning is associated with SYCP2 , MEI4 , and PRDM9 . Our results show that crossover positioning and rate/interference are driven by distinct genetic processes in female pigs and have the capacity to evolve independently.

Wild Soay sheep rams with large horns have more offspring, yet there is considerable genetic variation at RXFP2 , a locus strongly implicated in horn size (with different alleles conferring either large or small horns); this study finds that although the larger horn allele leads to more offspring, the smaller horn allele leads to increased survival, meaning heterozygous rams (which develop medium-sized horns) have high reproductive success and survival, providing a rare example of heterozygote advantage. Putting a dampener on male exuberance Males often deploy expensive and showy ornaments — antlers, plumes, sports cars — with the goal of attracting females. Because these ornaments are so advantageous, surely they should soon go to fixation? But no, there is always some genetic variation in the size or showiness of the display trait. This is usually explained as either due to the involvement of multiple genes or as a trade-off between the prominence of the male trait and female health. This study offers a third and disarmingly simple explanation: a trade-off between reproduction and survival. Soay rams with big horns have the most reproductive success, but there is considerable genetic variation, and many rams have very tiny horns. Variation in a single gene, RXFP2 , has been strongly implicated in horn size. The researchers show that although rams with big horns attract more mates, rams with small horns live longer. Heterozygotes, with middle-sized horns, are intermediate in longevity and reproductive success. Sexual selection, through intra-male competition or female choice, is assumed to be a source of strong and sustained directional selection in the wild 1 , 2 . 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 3 . 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 1 , 4 , 5 . 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 6 . 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, Ho P , 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 7 , 8 (‘good genes’) and sexually antagonistic selection 5 , 9 . 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.

Abstract Meiotic recombination is a fundamental feature of sexually reproducing species. It is often required for proper chromosome segregation and plays important role in adaptation and the maintenance of genetic diversity. The molecular mechanisms of recombination are remarkably conserved across eukaryotes, yet meiotic genes and proteins show substantial variation in their sequence and function, even between closely related species. Furthermore, the rate and distribution of recombination shows a huge diversity within and between chromosomes, individuals, sexes, populations, and species. This variation has implications for many molecular and evolutionary processes, yet how and why this diversity has evolved is not well understood. A key step in understanding trait evolution is to determine its genetic basis—that is, the number, effect sizes, and distribution of loci underpinning variation. In this perspective, I discuss past and current knowledge on the genetic basis of variation in recombination rate and distribution, explore its evolutionary implications, and present open questions for future research.

Background Recombination is a fundamental part of mammalian meiosis that leads to the exchange of large segments of DNA between homologous chromosomes and is therefore an important driver of genetic diversity in populations. In breeding populations, understanding recombination is of particular interest because it can break up unfavourable linkage phases between alleles and produce novel combinations of alleles that could be exploited in selection. In this study, we used dense single nucleotide polymorphism (SNP) genotype data and pedigree information to analyse individual and sex-specific variation and genetic architecture of recombination rates within and between five commercially selected pig breeds. Results In agreement with previous studies, recombination rates were higher in females than in males for all breeds and for all chromosomes, except 1 and 13, for which male rates were slightly higher. Total recombination rate differed between breeds but the pattern of recombination along the chromosomes was well conserved across breeds for the same sex. The autosomal linkage maps spanned a total length of 1731 to 1887 cM for males and of 2231 to 2515 cM for females. Estimates of heritability for individual autosomal crossover count ranged from 0.04 to 0.07 for males and from 0.08 to 0.11 for females. Fourteen genomic regions were found to be associated with individual autosomal crossover count. Of these, four were close to or within candidate genes that have previously been associated with individual recombination rates in pigs and other mammals, namely RNF212 , SYCP2 and MSH4 . Two of the identified regions included the PRDM7 and MEI1 genes, which are known to be involved in meiosis but have not been previously associated with variation in individual recombination rates. Conclusions This study shows that genetic variation in autosomal recombination rate persists in domesticated species under strong selection, with differences between closely-related breeds and marked differences between the sexes. Our findings support results from other studies, i.e., that individual crossover counts are associated with the RNF212 , SYCP2 and MSH4 genes in pig. In addition, we have found two novel candidate genes associated with the trait, namely PRDM7 and MEI1 .

Much of our knowledge of the drivers of immune variation, and how these responses vary over time, comes from humans, domesticated livestock or laboratory organisms. While the genetic basis of variation in immune responses have been investigated in these systems, there is a poor understanding of how genetic variation influences immunity in natural, untreated populations living in complex environments. Here, we examine the genetic architecture of variation in immune traits in the Soay sheep of St Kilda, an unmanaged population of sheep infected with strongyle gastrointestinal nematodes. We assayed IgA, IgE and IgG antibodies against the prevalent nematode Teladorsagia circumcincta in the blood plasma of > 3,000 sheep collected over 26 years. Antibody levels were significantly heritable (h2 = 0.21 to 0.57) and highly stable over an individual's lifespan. IgA levels were strongly associated with a region on chromosome 24 explaining 21.1% and 24.5% of heritable variation in lambs and adults, respectively. This region was adjacent to two candidate loci, Class II Major Histocompatibility Complex Transactivator (CIITA) and C-Type Lectin Domain Containing 16A (CLEC16A). Lamb IgA levels were also associated with the immunoglobulin heavy constant loci (IGH) complex, and adult IgE levels and lamb IgA and IgG levels were associated with the major histocompatibility complex (MHC). This study provides evidence of high heritability of a complex immunological trait under natural conditions and provides the first evidence from a genome-wide study that large effect genes located outside the MHC region exist for immune traits in the wild.

Recombination is a fundamental feature of sexual reproduction, ensuring proper disjunction, preventing mutation accumulation and generating new allelic combinations upon which selection can act. However it is also mutagenic, and breaks up favorable allelic combinations previously built up by selection. Identifying the genetic drivers of recombination rate variation is a key step in understanding the causes and consequences of this variation, how loci associated with recombination are evolving and how they affect the potential of a population to respond to selection. However, to date, few studies have examined the genetic architecture of recombination rate variation in natural populations. Here, we use pedigree data from ∼ 2,600 individuals genotyped at ∼ 38,000 SNPs to investigate the genetic architecture of individual autosomal recombination rate in a wild population of red deer (Cervus elaphus). Female red deer exhibited a higher mean and phenotypic variance in autosomal crossover counts (ACC). Animal models fitting genomic relatedness matrices showed that ACC was heritable in females (h2 = 0.12) but not in males. A regional heritability mapping approach showed that almost all heritable variation in female ACC was explained by a genomic region on deer linkage group 12 containing the candidate loci REC8 and RNF212B, with an additional region on linkage group 32 containing TOP2B approaching genome-wide significance. The REC8/RNF212B region and its paralogue RNF212 have been associated with recombination in cattle, mice, humans and sheep. Our findings suggest that mammalian recombination rates have a relatively conserved genetic architecture in both domesticated and wild systems, and provide a foundation for understanding the association between recombination loci and individual fitness within this population.

Runs of homozygosity (ROH) are pervasive in diploid genomes and expose the effects of deleterious recessive mutations, but how exactly these regions contribute to variation in fitness remains unclear. Here, we combined empirical analyses and simulations to explore the deleterious effects of ROH with varying genetic map lengths in wild Soay sheep. Using a long‐term dataset of 4879 individuals genotyped at 417K SNPs, we found that inbreeding depression increases with ROH length. A 1% genomic increase in long ROH (>12.5 cM) reduced the odds of first‐year survival by 12.4% compared to only 7.7% for medium ROH (1.56–12.5 cM), whereas short ROH (<1.56 cM) had no effect on survival. We show by forward genetic simulations that this is predicted: compared to shorter ROH, long ROH will have higher densities of deleterious alleles, with larger average effects on fitness and lower population frequencies. Taken together, our results are consistent with the idea that the mutation load decreases in older haplotypes underlying shorter ROH, where purifying selection has had more time to purge deleterious mutations. Finally, our study demonstrates that strong inbreeding depression can persist despite ongoing purging in a historically small population.