Stable recombination hotspots in birds

Abstract

The DNA-binding protein PRDM9 has a critical role in specifying meiotic recombination hotspots in mice and apes, but appears to be absent from other vertebrate species, including birds. To study the evolution and determinants of recombination in species lacking PRDM9, we inferred fine-scale genetic maps from population resequencing data for two bird species, the zebra finch Taeniopygia guttata and the long-tailed finch Poephila acuticauda. We find that both species have hotspots, which are enriched near functional genomic elements. Unlike in mice and apes, the two species share most hotspots, with conservation seemingly extending over tens of millions of years. These observations suggest that in the absence of PRDM9, recombination targets functional features that both enable access to the genome and constrain its evolution.Meiotic recombination is a ubiquitous and fundamental genetic process that shapes variation in populations, yet our understanding of its underlying mechanisms is based on a handful of model organisms, scattered throughout the tree of life. One pattern shared among most sexually reproducing species is that meiotic recombination tends to occur in short segments of 100s to 1000s of base pairs, termed "recombination hotspots" (1). In apes and mice, the location of hotspots is largely determined by PRDM9, a zinc-finger protein that binds to specific motifs in the genome during meiotic prophase and generates H3K4me3 marks, eventually leading to double-strand breaks (DSBs) and both crossover and non-crossover + to whom correspondence should be addressed. * co-first authors [2][3][4][5]. In mammals, the zinc-finger domain of PRDM9 evolves quickly, with evidence of positive selection on residues in contact with DNA (2, 6), and as a result, there is rapid turnover of hotspot locations across species, subspecies, and populations (7-10). Europe PMC Funders GroupAlthough PRDM9 plays a pivotal role in controlling recombination localization in mice and apes, many species lacking PRDM9 nonetheless have hotspots (6). An artificial example is provided by mice knockouts for PRDM9. Despite being sterile, they make similar numbers of DSBs as wild-type mice, and their recombination hotspots appear to default to residual H3K4me3 mark locations, notably at promoters (10). A natural but puzzling example is provided by canids, which carry premature stop codons in PRDM9 yet are able to recombine and remain fertile (11,12). Like in mouse PRDM9 knockouts, in dogs and in other species without PRDM9 such as the yeast Saccharomyces cerevisae and the plant Arabidopsis thaliana, hotspots tend to occur at promoters or other regions with promoter-like features (11, 13,14). In yet other taxa without PRDM9, including Drosophila species (15), honeybees (16), and Caenorhabditis elegans (17), short, intense recombination hotspots appear to be absent altogether.To further explore how the absence of PRDM9 shapes the fine-scale recombination landscape and impacts its evolution, we turn to birds, because an analysis of the chick...

Health and population effects of rare gene knockouts in adult humans with related parents

“…When using all 37 (respectively 42) crossovers we get consistent results: for the PRDM9 A Union DSB hotspots: NA12878 duo 55 …”

Evidence of linked selection on the Z chromosome of hybridizing hummingbirds*

“…If this hypothesis is true, we would expect to see similar patterns of differentiation and diversity across multiple species pairs sharing a similar recombination landscape, as is thought to occur in birds (Singhal et al. ).…”

“…Specifically, we expect the effects of background selection on linked neutral regions to be strongest when recombination rate is low (Charlesworth ), and because birds have a relatively conserved recombination landscape (Singhal et al. ; Kawakami et al. ), this would lead to a highly correlated landscape of genomic diversity.…”

Nonparadoxical evolutionary stability of the recombination initiation landscape in yeast

“…Finally, we note that available evidence in plants, birds, and canids — all apparently lacking a PRDM9-like hotspot targeting mechanism — point to Spo11 acting preferentially at promoters, CpG islands, and/or other genomic elements that are under selective constraint to maintain functions separate from being Spo11 targets (39–41). In finches, high-resolution recombination maps inferred from population genetic data reveal evolutionary stability of recombination hotspots, analogous to Saccharomyces but wholly unlike PRDM9-reliant apes or mice (41).…”

“…In finches, high-resolution recombination maps inferred from population genetic data reveal evolutionary stability of recombination hotspots, analogous to Saccharomyces but wholly unlike PRDM9-reliant apes or mice (41). Thus, not only is it untrue that recombination initiation landscapes inevitably evolve rapidly, but conservation is likely to be a common pattern for many sexual species.…”