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

Molecular Biology and Evolution, Journal Year: 2024, Volume and Issue: 41(7)

Published: July 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.

Language: Английский

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

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(1), P. e3002950 - e3002950

Published: Jan. 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.

Language: Английский

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High prevalence of PRDM9-independent recombination hotspots in placental mammals

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(23)

Published: May 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.

Language: Английский

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universalmotif: An R package for biological motif analysis

The Journal of Open Source Software, Journal Year: 2024, Volume and Issue: 9(100), P. 7012 - 7012

Published: Aug. 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")

Language: Английский

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

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: Aug. 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.

Language: Английский

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

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

Published: June 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.

Language: Английский

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Conserved features of recombination control in vertebrates

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(1), P. e3002959 - e3002959

Published: Jan. 7, 2025

A recent study in PLOS Biology on the epigenetic recombination regulator PRDM9 salmonid fish reveals that its function has been preserved across vertebrates for hundreds of millions years, with rapidly evolving DNA-binding domains being a defining attribute.

Language: Английский

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Germline mutation rates and fine-scale recombination parameters in zebra finch

PLoS Genetics, Journal Year: 2025, Volume and Issue: 21(4), P. e1011661 - e1011661

Published: April 15, 2025

Most of our understanding the fundamental processes mutation and recombination stems from a handful disparate model organisms pedigree studies mammals, with little known about other vertebrates. To gain broader comparative perspective, we focused on zebra finch ( Taeniopygia castanotis ), which, like birds, differs mammals in its karyotype (which includes many micro-chromosomes), mechanism by which is directed to genome, aspects ontogenesis. We collected genome sequences three generation pedigrees that provide information 80 meioses, inferring 202 single-point de novo mutations, 1,088 crossovers, 275 non-crossovers. On basis, estimated sex-averaged rate 5.0 × 10 -9 per base pair generation, par have similar time (~2–3 years). Also as found paternal germline bias at later stages gametogenesis (of 1.7:1) but no discernible difference between sexes early development. Examining patterns, crossover macro-chromosomes 0.93 cM/Mb, pronounced enrichment crossovers near telomeres. In contrast, non-crossover rates are more uniformly distributed. micro-chromosomes, substantially higher (3.96 cM/Mb), accordance homeostasis, both events At finer scale, overlap CpG islands often than expected chance, absence PRDM9. Estimates degree GC-biased gene conversion (59%), mean tract length (~32 bp), non-crossover-to-crossover ratio (5.4:1) all comparable those reported primates mice. Therefore, properties resolutions remain over large phylogenetic distances.

Language: Английский

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