Extreme Recombination Frequencies Shape Genome Variation and Evolution in the Honeybee, Apis mellifera

Abstract

Meiotic recombination is a fundamental cellular process, with important consequences for evolution and genome integrity. However, we know little about how recombination rates vary across the genomes of most species and the molecular and evolutionary determinants of this variation. The honeybee, Apis mellifera, has extremely high rates of meiotic recombination, although the evolutionary causes and consequences of this are unclear. Here we use patterns of linkage disequilibrium in whole genome resequencing data from 30 diploid honeybees to construct a fine-scale map of rates of crossing over in the genome. We find that, in contrast to vertebrate genomes, the recombination landscape is not strongly punctate. Crossover rates strongly correlate with levels of genetic variation, but not divergence, which indicates a pervasive impact of selection on the genome. Germ-line methylated genes have reduced crossover rate, which could indicate a role of methylation in suppressing recombination. Controlling for the effects of methylation, we do not infer a strong association between gene expression patterns and recombination. The site frequency spectrum is strongly skewed from neutral expectations in honeybees: rare variants are dominated by AT-biased mutations, whereas GC-biased mutations are found at higher frequencies, indicative of a major influence of GC-biased gene conversion (gBGC), which we infer to generate an allele fixation bias 5 – 50 times the genomic average estimated in humans. We uncover further evidence that this repair bias specifically affects transitions and favours fixation of CpG sites. Recombination, via gBGC, therefore appears to have profound consequences on genome evolution in honeybees and interferes with the process of natural selection. These findings have important implications for our understanding of the forces driving molecular evolution.

Author Summary

Evolution results from changes in allele frequencies in populations. The main forces that cause such changes are natural selection and random genetic drift. However, an additional process, GC-biased gene conversion (gBGC), associated with meiotic recombination, affects the probability that alleles are passed from one generation to the next. The honeybee, Apis mellifera, has extremely high recombination rates—more than 20 times to those observed in humans. However, the reason for this is unknown and the effects of such high recombination rates on evolution are not well understood. Here we use patterns of genetic variation in the genomes of 30 honeybees to infer variation in the rate of recombination across the genome. We find that recombination rates and levels of genetic variation are strongly correlated, which is indicative of a pervasive impact of natural selection on genetic variation. We also infer a major role of DNA methylation in determining recombination rates in genes. Patterns of genetic variation appear to be strongly skewed due to the effects of gBGC, suggesting that recombination generates a bias in transmission of alleles during meiosis. This process seems to be interfering with the efficacy of selection at removing deleterious alleles and favouring beneficial ones. Recombination therefore has a huge impact on genetic variation and evolution in honeybees and appears to play a dominant role in genome evolution.