Down the Penrose stairs, or how selection for fewer recombination hotspots maintains their existence

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Oct. 13, 2023

In many species, meiotic recombination events tend to occur in narrow intervals of the genome, known as hotspots. humans and mice, double strand break (DSB) hotspot locations are determined by DNA-binding specificity zinc finger array PRDM9 protein, which is rapidly evolving at residues contact with DNA. Previous models explained this rapid evolution terms need restore binding sites lost gene conversion over time, under assumption that more always leads DSBs. This assumption, however, does not align current evidence. Recent experimental work indicates on both homologs facilitates DSB repair, absence sufficient symmetric disrupts meiosis. We therefore consider an alternative hypothesis: driven because its role coupling formation efficient repair. To end, we model from first principles: dynamics population genetic processes govern sites. show loss a small number strong use greater weaker ones, resulting sharp reduction favoring new alleles smaller set decrease, turn, drives evolutionary turnover. Our results suggest advantage limiting used effectively, rather than increasing net binding. By extension, our suggests hotspots may have been increase efficiency repair and/or homolog pairing.

Language: Английский

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PRDM9 drives the location and rapid evolution of recombination hotspots in salmonids

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 7, 2024

Abstract In many eukaryotes, meiotic recombination occurs preferentially at discrete sites, called hotspots. various lineages, hotspots are located in regions with promoter-like features and evolutionarily stable. Conversely, some mammals, driven by PRDM9 that targets away from promoters. Paradoxically, induces the self-destruction of its this triggers an ultra-fast evolution mammalian is ancestral to all animals, suggesting a critical importance for program, but has been lost lineages surprisingly little effect on meiosis success. However, it unclear whether function described mammals shared other species. To investigate this, we analyzed landscape several salmonids, genome which harbors one full-length truncated paralogs. We identified initiation sites Oncorhynchus mykiss mapping DNA double-strand breaks (DSBs). found DSBs clustered positioned promoters, enriched H3K4me3 H3K4me36 marks location depended genotype Prdm9 . observed high level polymorphism zinc finger domain , not Moreover, population-scaled maps O. kisutch Salmo salar revealed rapid turnover caused target motif erosion. Our results imply conserved across vertebrates peculiar evolutionary runaway active hundred million years.

Language: Английский

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Increased Positive Selection in Highly Recombining Genes Does not Necessarily Reflect an Evolutionary Advantage of Recombination

Molecular Biology and Evolution, Journal Year: 2024, Volume and Issue: 41(6)

Published: May 30, 2024

Abstract It is commonly thought that the long-term advantage of meiotic recombination to dissipate genetic linkage, allowing natural selection act independently on different loci. thus theoretically expected genes with higher rates evolve under more effective selection. On other hand, often associated GC-biased gene conversion (gBGC), which interferes by promoting fixation deleterious GC alleles. To test these predictions, several studies assessed whether was in highly recombining (due dissipation linkage) or less gBGC), assuming a fixed distribution fitness effects (DFE) for all genes. In this study, I directly derive DFE from gene’s evolutionary history (shaped mutation, selection, drift, and gBGC) empirical landscapes. show have experienced high levels gBGC are fit opportunities beneficial mutations. Only small decrease genome-wide intensity leads mutations, particularly This results increased positive not caused Additionally, death hotspot can lead dN/dS than its birth, but substitution patterns biased towards AT, only at selected positions. shows controlling bias therefore sufficient rule out contribution signatures accelerated evolution. Finally, although does affect probability GC-conservative altering DFE, also significantly nonsynonymous patterns.

Language: Английский

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Genetic architecture of individual meiotic crossover rate and distribution in Atlantic Salmon

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Nov. 22, 2023

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

Language: Английский

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High prevalence of Prdm9-independent recombination hotspots in placental mammals

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 17, 2023

Abstract In many mammals, recombination events are concentrated into hotspots directed by a sequence specific DNA-binding protein named Prdm9. This facilitates chromosome pairing and its inactivation has been shown to induce fertility losses in mice rats. Intriguingly, Prdm9 lost several times vertebrates, notably among it pseudogenized the ancestor of canids (dogs, wolves foxes). When this gene is inactive, either naturally dogs, or through knock-out experiments mice, still exist, but they tend occur promoter-like features such as CpG islands. It thus proposed that one role could be direct away from those Prdm9-independent hotspots. However, ability assessed only handful species, clear picture how much occurs outside Prdm9-directed mammals lacking. study, we derived an estimator past activity based on signatures GC-biased conversion substitution patterns. We applied quantify 52 species boreoeutherian mammals. observed wide range rate at these loci: (such humans, some felids cetaceans) show deficit recombination, while majority display peak recombination. Our results demonstrate can co-exist their co-existence seem rule rather than exception.

Language: Английский

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Rapid evolution of recombination landscapes during the divergence of cichlid ecotypes in Lake Masoko

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 23, 2024

Abstract Meiotic recombination is fundamental to evolution of sexually reproducing organisms and differences in rates are important during rapid adaptation organismal diversification. Many unknowns remain regarding how why landscapes evolve nature. Here, we reconstruct maps based on linkage disequilibrium use subsampling simulations show that fine-scale differ substantially between two cichlid fish ecotypes Astatotilapia calliptera diverged only ∼2,500 generations ago. The observed results not driven by PDRM9, whose binding sites do any relationship this species. We regions where histories have non-random distribution across chromosomes. They associated with, but partially explained, high divergence allele frequency ( F ST ) / or nucleotide diversity. also found 47 large haplotype blocks polymorphic Lake Masoko, cover 21% the genome, appear include inversions, contribute disproportionately recombination. Only a small number them elevated . While some old likely maintained balancing selection, for most, age ancestry close genome-wide average. Among blocks, there strong clear association degree ecotype clustering individual heterozygosity. Overall, our work provides holistic view changes early stages speciation with gene flow advances understanding combinatorial basis evolution.

Language: Английский

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The GC-content at the 5’ends of human protein-coding genes is undergoing mutational decay

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 14, 2024

Abstract In vertebrates, most protein-coding genes have a peak of GC-content near their 5’ transcriptional start site (TSS). This feature promotes both the efficient nuclear export and translation mRNAs. Despite importance for RNA metabolism, its general features, origin, maintenance remain mysterious. We investigated evolutionary forces shaping at (TSS) through comparative genomic analysis nucleotide substitution rates between different species by examining human de novo mutations. Our data suggests that GC-peaks TSSs were present in last vertebrate common ancestor are largely dictated recombination patterns. observe primates rodents, where is directed away from PRDM9, gene currently undergoing mutational decay. canids, which lack PRDM9 perform TSSs, increasing. These patterns extend into open reading frame affecting regions, we show changes due to affect synonymous codon position choices frame. results indicate although high may be shaped selective pressures enhance expression, dynamics mammals recombination.

Language: Английский

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Increased positive selection in highly recombining genes is not an evidence for an evolutionary advantage of recombination

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 17, 2024

Abstract It is commonly thought that the long-term advantage of meiotic recombination to dissipate genetic linkage, allowing natural selection act independently on different loci. thus theoretically expected genes with higher rates evolve under more effective selection. On other hand, often associated GC-biased gene conversion (gBGC), which interferes by promoting fixation deleterious GC alleles. To test these predictions, several studies assessed whether was in highly recombining (due dissipation linkage) or less gBGC), assuming a fixed distribution fitness effects (DFE) for all genes. In this study, I directly derive DFE from gene’s evolutionary history (shaped mutation, selection, drift and gBGC) empirical landscapes. show have experienced high levels gBGC are fit opportunities beneficial mutations. Only small decrease genome-wide intensity leads mutations, particularly This results increased positive not caused Additionally, death hotspot can lead dN/dS than its birth, but substitution patterns biased towards AT, only at selected positions. shows controlling bias therefore sufficient rule out contribution signatures accelerated evolution. Finally, although does affect probability GC-conservative altering DFE, also significantly non-synonymous patterns.

Language: Английский

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Ubiquitous recombination gradients within plant genic regions shaped by recombination hotspots

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 13, 2023

Abstract During the meiosis of many eukaryote species, crossovers tend to occur within narrow regions called recombination hotspots. In plants, it is generally thought that gene regulatory sequences, especially promoters and 5’-3’ untranslated regions, are enriched in hotspots, but this has been characterized a handful species only. We also lack clear description fine-scale variation rates genic little known about hotspot position intensity plants. To address question we constructed maps from genetic polymorphism data inferred hotspots eleven plant species. detected gradients both 5’ 3’ most yet varied shape depending on specific locations structure. further characterize gradients, decomposed them according structure by rank number exons. generalized previously observed pattern organized around boundaries coding promoters. However, our results provided new insight into relative importance end genes some possible location away Variation among seemed driven more than differences size or Our shed light at very fine scale, detailed whole genome averaged estimates used so far, revealing diversity complexity emerging interaction between

Language: Английский

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