A simple expression for the strength of selection on recombination generated by interference among mutations

One of the most widely cited hypotheses to explain the evolutionary maintenance of genetic recombination states that the reshuffling of genotypes at meiosis increases the efficiency of natural selection by reducing interference among selected loci. However, and despite several decades of theoretical work, a quantitative estimation of the possible selective advantage of a mutant allele increasing chromosomal map length (the average number of cross-overs at meiosis) remains difficult. This article derives a simple expression for the strength of selection acting on a modifier gene affecting the genetic map length of a whole chromosome or genome undergoing recurrent mutation. In particular, it shows that indirect selection for recombination caused by interference among mutations is proportional to NeU2/NeR3, where Ne is the effective population size, U is the deleterious mutation rate per chromosome, and R is the chromosome map length. Indirect selection is relatively insensitive to the fitness effects of deleterious alleles, epistasis, or the genetic architecture of recombination rate variation and may compensate for substantial costs associated with recombination when linkage is tight. However, its effect generally stays weak in large, highly recombining populations.

Genomics of recombination rate variation in temperature-evolved Drosophila melanogaster populations

Meiotic recombination is a critical process that ensures proper segregation of chromosome homologues through DNA double strand break repair mechanisms. Rates of recombination are highly variable among various taxa, within species, and within genomes with far-reaching evolutionary and genomic consequences. The genetic basis of recombination rate variation is therefore crucial in the study of evolutionary biology but remains poorly understood. In this study we took advantage of a set of experimental temperature-evolved populations of Drosophila melanogaster with heritable differences in recombination rates depending on the temperature regime in which they evolved. We performed whole genome sequencing and identified several chromosomal regions that appear to be divergent depending on temperature regime. In addition, we identify a set of single nucleotide polymorphisms and associated genes with significant differences in allele frequency when the different temperature populations are compared. Further refinement of these gene candidates emphasizing those expressed in the ovary and associated with DNA binding reveals numerous potential candidate genes such as Hr38, EcR, and mamo responsible for observed differences in recombination rates in these experimental evolution lines thus providing insight into the genetic basis of recombination rate variation.

Genomic Features of Parthenogenetic Animals

Evolution without sex is predicted to impact genomes in numerous ways. Case studies of individual parthenogenetic animals have reported peculiar genomic features that were suggested to be caused by their mode of reproduction, including high heterozygosity, a high abundance of horizontally acquired genes, a low transposable element load, or the presence of palindromes. We systematically characterized these genomic features in published genomes of 26 parthenogenetic animals representing at least 18 independent transitions to asexuality. Surprisingly, not a single feature was systematically replicated across a majority of these transitions, suggesting that previously reported patterns were lineage-specific rather than illustrating the general consequences of parthenogenesis. We found that only parthenogens of hybrid origin were characterized by high heterozygosity levels. Parthenogens that were not of hybrid origin appeared to be largely homozygous, independent of the cellular mechanism underlying parthenogenesis. Overall, despite the importance of recombination rate variation for the evolution of sexual animal genomes, the genome-wide absence of recombination does not appear to have had the dramatic effects which are expected from classical theoretical models. The reasons for this are probably a combination of lineage-specific patterns, the impact of the origin of parthenogenesis, and a survivorship bias of parthenogenetic lineages.

Variants at RNF212 and RNF212B are associated with recombination rate variation in Soay sheep (Ovis aries)

Meiotic recombination is a ubiquitous feature of sexual reproduction, ensuring proper disjunction of homologous chromosomes, and creating new combinations of alleles upon which selection can act. By identifying the genetic drivers of recombination rate variation, we can begin to understand its evolution. Here, we revisit an analysis investigating the genetic architecture of gamete autosomal crossover counts (ACC) in a wild population of Soay sheep (Ovis aries) using a much larger dataset (increasing from 3,300 to 7,235 gametes and from ∼39,000 to ∼415,000 SNPs for genome-wide association analysis). Animal models fitting genomic relatedness confirmed that ACC was heritable in both females (h2 = 0.18) and males (h2 = 0.12). Genome-wide association studies identified two regions associated with ACC variation. A region on chromosome 6 containing RNF212 explained 46% of heritable variation in female ACC, but was not associated with male ACC, confirming the previous finding. A region on chromosome 7 containing RNF212B explained 20-25% of variation in ACC in both males and females. Both RNF212 and RNF212B have been repeatedly associated with recombination rate in other mammal species. These findings confirm that moderate to large effect loci can underpin ACC variation in wild mammals, and provide a foundation for further studies on the evolution of recombination rates.

Genetic architecture and lifetime dynamics of inbreeding depression in a wild mammal

Inbreeding depression is a phenomenon of long-standing importance, but we know surprisingly little about its genetic architecture, precise effects and life-history dynamics in wild populations. Here, we combined 417K imputed SNP genotypes for 5952 wild Soay sheep with detailed long-term life-history data to explore inbreeding depression on a key fitness component, annual survival. Inbreeding manifests in long runs of homozygosity (ROH) and these are abundant in Soay sheep, covering on average 24% of the autosomal genome and up to 50% in the most inbred individuals. The ROH landscape is shaped by recombination rate variation and differs widely across the genome, including islands where up to 87% of the population have an ROH and deserts where the ROH prevalence is as low as 4%. We next quantified individual inbreeding as the proportion of the autosomal genome in ROH (FROH) and estimated its effect on annual survival. The consequences of inbreeding are severe; a 10% increase in FROH was associated with a 68% [95% CI 55-78%] decrease in the odds of survival. However, the strength of inbreeding depression is dynamic across the lifespan. We estimate depression to peak in young adults, to decrease into older ages and to be weaker in lambs, where inbreeding effects are possibly buffered by maternal care. Finally, using a genome-wide association scan on ROH, we show that inbreeding causes depression predominantly through many loci with small effects, but we also find three regions in the genome with putatively strongly deleterious mutations. Our study reveals population and genome-wide patterns of homozygosity caused by inbreeding and sheds light on the strength, dynamics and genetic architecture of inbreeding depression in a wild mammal population.

Genetics of recombination rate variation in the pig

BackgroundIn this paper, we estimated recombination rate variation within the genome and between individuals in the pig using multiocus iterative peeling for 150,000 pigs across nine genotyped pedigrees. We used this to estimate the heritability of recombination and perform a genome-wide association study of recombination in the pig.ResultsOur results confirmed known features of the pig recombination landscape, including differences in chromosome length, and marked sex differences. The recombination landscape was repeatable between lines, but at the same time, the lines also showed differences in average genome-wide recombination rate. The heritability of genome-wide recombination was low but non-zero (on average 0.07 for females and 0.05 for males). We found three genomic regions associated with recombination rate, one of them harbouring the RNF212 gene, previously associated with recombination rate in several other species.ConclusionOur results from the pig agree with the picture of recombination rate variation in vertebrates, with low but nonzero heritability, and a major locus that is homologous to one detected in several other species. This work also highlights the utility of using large-scale livestock data to understand biological processes.