Understanding the Genetic Basis of Variation in Meiotic Recombination: Past, Present, and Future

Molecular Biology and Evolution, Год журнала: 2024, Номер 41(7)

Опубликована: Июль 1, 2024

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

Язык: Английский

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High prevalence of PRDM9-independent recombination hotspots in placental mammals

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(23)

Опубликована: Май 29, 2024

In many mammals, recombination events are concentrated in hotspots directed by a sequence-specific DNA-binding protein named PRDM9. Intriguingly, PRDM9 has been lost several times vertebrates, and notably among it pseudogenized the ancestor of canids. absence PRDM9, tend to occur promoter-like features such as CpG islands. It thus proposed that one role could be direct away from PRDM9-independent hotspots. However, ability assessed only handful species, clear picture how much occurs outside PRDM9-directed mammals is still lacking. this study, we derived an estimator past activity based on signatures GC-biased gene conversion substitution patterns. We quantified 52 species boreoeutherian mammals. observe wide range rates at these loci: (such mice, humans, some felids, or cetaceans) show deficit recombination, while majority display peak recombination. Our results demonstrate can coexist their coexistence appears rule rather than exception. Additionally, location relatively more stable hotspots, but nevertheless evolve slowly concert with DNA hypomethylation.

Язык: Английский

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PRDM9 drives the location and rapid evolution of recombination hotspots in salmonid fish

PLoS Biology, Год журнала: 2025, Номер 23(1), С. e3002950 - e3002950

Опубликована: Янв. 6, 2025

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 H3K36me3 location depended genotype Prdm9 . observed high level polymorphism zinc finger domain , indicating diversification positive selection. 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.

Язык: Английский

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universalmotif: An R package for biological motif analysis

The Journal of Open Source Software, Год журнала: 2024, Номер 9(100), С. 7012 - 7012

Опубликована: Авг. 19, 2024

Sequence motifs are an important concept in molecular biology, as specific repeating patterns DNA, RNA and proteins form the basis of biological regulation.Identifying characterizing these is therefore a part studying various aspects cellular processes, such gene regulation, transcript stability, protein function.Many programs have been developed over years to tackle tasks, though their interoperability remains poor.The universalmotif package has two main goals: serve go-between for most common motif Bioconductor packages used by research community, provide robust set tools basic analysis manipulation R. Tools sequence manipulation, scanning, enrichment, comparison, shuffling P-value computation included. InstallationThe project including its extensive documentation hosted on Bioconductor, with pre-built binaries available macOS Windows (and installation from source all platforms).Installation takes place within R using BiocManager package, which itself can be installed CRAN:install.packages("BiocManager") BiocManager::install("universalmotif")

Язык: Английский

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

Genome biology, Год журнала: 2024, Номер 25(1)

Опубликована: Авг. 13, 2024

Abstract Background 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 investigate evolutionary forces shaping at (TSS) through comparative genomic analysis nucleotide substitution rates between different species by examining human de novo mutations. Results Our data suggests that GC-peaks TSSs were present in last common ancestor amniotes, likely vertebrates. observe apes rodents, where recombination is directed away from PRDM9, end gene currently undergoing mutational decay. canids, which lack PRDM9 perform TSSs, increasing. show these patterns extend into open reading frame, thus impacting synonymous codon position choices. Conclusions results indicate dynamics this GC-peak amniotes largely shaped historic recombination. Since decay towards mutation rate equilibrium default state non-functional DNA, observed decrease rodents indicates not being maintained selection on those species.

Язык: Английский

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

eLife, Год журнала: 2023, Номер 12

Опубликована: Окт. 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.

Язык: 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, Год журнала: 2024, Номер 41(6)

Опубликована: Май 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.

Язык: Английский

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Determinants of de novo mutations in extended pedigrees of 43 dog breeds

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 5, 2024

Abstract Intensive breeding of dogs has had dramatic effects on genetic variants underlying phenotypes. To investigate whether this also affected mutation rates, we deep-sequenced pedigrees from 43 different dog breeds representing 404 trios. We find that the rate is remarkably stable across and predominantly influenced by variation in parental ages. The effect paternal age per year rates approximately 1.5 times greater than humans, suggesting elevated yearly only partially attributed to earlier reproduction. While there no significant overall rate, larger accumulate proportionally more mutations development small breeds. Interestingly, a 2.6 CG Islands (CGIs) compared remaining genome dogs, unlike where difference. Our estimated recombination 10 estimates humans. ascribe these fact canids have lost PRDM9-directed draw away CGIs. In conclusion, our study sheds light stability processes disparities accumulation reflecting influence differences growth patterns among breeds, impact PRDM9 gene loss de novo canids.

Язык: Английский

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Diversity in Recombination Hotspot Characteristics and Gene Structure Shape Fine-Scale Recombination Patterns in Plant Genomes

Molecular Biology and Evolution, Год журнала: 2024, Номер 41(9)

Опубликована: Сен. 1, 2024

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 11 plant species. detected gradients 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, revealing diversity complexity emerging interaction between

Язык: Английский

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

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Ноя. 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.

Язык: Английский

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