Evolution of the germline mutation rate across vertebrates

Nature, Journal Year: 2023, Volume and Issue: 615(7951), P. 285 - 291

Published: March 1, 2023

The germline mutation rate determines the pace of genome evolution and is an evolving parameter itself1. However, little known about what its evolution, as most studies rates have focused on single species with different methodologies2. Here we quantify across vertebrates by sequencing comparing high-coverage genomes 151 parent-offspring trios from 68 mammals, fishes, birds reptiles. We show that per-generation varies among a factor 40, being higher for males than females in mammals birds, but not reptiles fishes. generation time, age at maturity species-level fecundity are key life-history traits affecting this variation species. Furthermore, long-term effective population sizes tend to lower per generation, providing support drift barrier hypothesis3. exceptionally high yearly domesticated animals, which been continually selected including shorter times, further importance time rates. Overall, our comparative analysis pedigree-based provides ecological insights vertebrates.

Language: Английский

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Patterns of recombination in snakes reveal a tug-of-war between PRDM9 and promoter-like features

Science, Journal Year: 2024, Volume and Issue: 383(6685)

Published: Feb. 22, 2024

In some mammals, notably humans, recombination occurs almost exclusively where the protein PRDM9 binds, whereas in vertebrates lacking an intact

Language: Английский

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Experimental estimates of germline mutation rate in eukaryotes: a phylogenetic meta-analysis

Evolution Letters, Journal Year: 2023, Volume and Issue: 7(4), P. 216 - 226

Published: June 19, 2023

Mutation is the ultimate source of all genetic variation, and over last 10 years ready availability whole-genome sequencing has permitted direct estimation mutation rate for many non-model species across tree life. In this meta-analysis, we make a comprehensive search literature estimates in eukaryotes, identifying 140 accumulation (MA) parent-offspring (PO) studies covering 134 species. Based on these data, revisit differences single-nucleotide (SNM) between different phylogenetic lineages update known relationships generation time, genome size, nucleotide diversity-while accounting nonindependence. We do not find significant difference MA PO estimated rates, but confirm that mammal plant have higher rates than arthropods unicellular eukaryotes lowest rates. are with longer times larger sizes, even when relationships. Moreover, although diversity positively correlated rate, gradient relationship significantly less one (on logarithmic scale), consistent populations smaller effective size. For 29 which data available, indel short deletions generally more common insertions. Nevertheless, despite recent progress, no either SNM or available majority deeply branching eukaryotic lineages-or most animal phyla. Even among charismatic megafauna, experimental remain unknown amphibia scarce reptiles fish.

Language: Английский

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Meiotic DNA breaks drive multifaceted mutagenesis in the human germ line

Science, Journal Year: 2023, Volume and Issue: 382(6674)

Published: Nov. 30, 2023

Meiotic recombination commences with hundreds of programmed DNA breaks; however, the degree to which they are accurately repaired remains poorly understood. We report that meiotic break repair is eightfold more mutagenic for single-base substitutions than was previously understood, leading de novo mutation in one four sperm and 12 eggs. Its impact on indels structural variants even higher, 100- 1300-fold increases rates per break. uncovered new mutational signatures footprints relative sites, implicate unexpected biochemical processes error-prone mechanisms, including translesion synthesis end joining repair. provide evidence these mechanisms drive mutagenesis human germ lines lead disruption genes genome wide.

Language: Английский

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Unprecedented female mutation bias in the aye-aye, a highly unusual lemur from Madagascar

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(2), P. e3003015 - e3003015

Published: Feb. 7, 2025

Every mammal studied to date has been found have a male mutation bias: parents transmit more de novo mutations offspring than female parents, contributing increasingly with age. Although male-biased for 75 years, its causes are still debated. One obstacle understanding this pattern is near universality—without variation in bias, it difficult find an underlying cause. Here, we present new data on multiple pedigrees from two primate species: aye-ayes ( Daubentonia madagascariensis ), member of the strepsirrhine primates, and olive baboons Papio anubis ). In stark contrast across mammals, much larger effect maternal age paternal rates aye-aye. addition, older aye-aye mothers substantially fathers. We carry out both computational experimental validation our results, contrasting them results other primates using same methodologies. Further, analyze set DNA repair replication genes identify candidate that may be responsible change bias observed aye-ayes. Our demonstrate not immutable trait, but rather one can evolve between closely related species. Further work (and possibly lemuriform primates) should help explain molecular basis sex-biased mutation.

Language: Английский

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De novo Mutations in Domestic Cat are Consistent with an Effect of Reproductive Longevity on Both the Rate and Spectrum of Mutations

Molecular Biology and Evolution, Journal Year: 2022, Volume and Issue: 39(7)

Published: June 30, 2022

The mutation rate is a fundamental evolutionary parameter with direct and appreciable effects on the health function of individuals. Here, we examine this important in domestic cat, beloved companion animal as well valuable biomedical model. We estimate 0.86 × 10-8 per bp generation for cat (at an average parental age 3.8 years). find evidence significant paternal effect, more mutations transmitted by older sires. Our analyses suggest that human have accrued similar numbers germline before reaching sexual maturity. per-generation 28% lower than what has been observed humans, but consistent shorter time cat. Using model reproductive longevity, which takes into account differences to maturity, are able explain much difference rates between species. further apply our longevity novel analysis spectra spectrum resembles at younger reproduction. Together, these results implicate changes life-history driver evolution As first observation effect outside rodents primates, also phenomenon may be universal among mammals.

Language: Английский

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Eighty million years of rapid evolution of the primate Y chromosome

Nature Ecology & Evolution, Journal Year: 2023, Volume and Issue: 7(7), P. 1114 - 1130

Published: June 2, 2023

Language: Английский

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Somatic mutations in aging and disease

GeroScience, Journal Year: 2024, Volume and Issue: 46(5), P. 5171 - 5189

Published: March 15, 2024

Language: Английский

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Direct Measurement of the Mutation Rate and Its Evolutionary Consequences in a Critically Endangered Mollusk

Molecular Biology and Evolution, Journal Year: 2025, Volume and Issue: 42(1)

Published: Jan. 1, 2025

Abstract The rate at which mutations arise is a fundamental parameter of biology. Despite progress in measuring germline mutation rates across diverse taxa, such estimates are missing for much Earth's biodiversity. Here, we present the first estimate from phylum Mollusca. We sequenced three pedigreed families white abalone Haliotis sorenseni, long-lived, large-bodied, and critically endangered mollusk, estimated de novo 8.60 × 10−9 single nucleotide per site generation. This similar to measured vertebrates with comparable generation times longevity abalone, higher than faster-reproducing invertebrates. spectrum also that seen vertebrate species, although an excess rare C > A polymorphisms wild individuals suggests modifier allele or environmental exposure may have once increased rates. use our infer baseline effective population sizes (Ne) multiple Pacific find persisted over most their evolutionary history as large stable populations, contrast extreme fluctuations recent small census day. then timing pattern evolution genus Haliotis, was previously unknown due few fossil calibrations. Our findings important step toward understanding they establish key conservation genomics research mollusks.

Language: Английский

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Mutational signature analyses in multi-child families reveal sources of age-related increases in human germline mutations

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Nov. 6, 2024

Abstract Whole-genome sequencing studies of parent–offspring trios have provided valuable insights into the potential impact de novo mutations (DNMs) on human health and disease. However, molecular mechanisms that drive DNMs are unclear. Studies with multi-child families can provide important insight causes inter-family variability in DNM rates but they highly limited. We characterized 2479 single nucleotide variants (SNVs) 13 Mexican-American ethnicity. observed a strong paternal age effect validated SNVs extensive yearly rate increase. Children older fathers showed more C > T transitions at CpG sites than children from younger fathers. Validated were examined against one cancer (COSMIC) two non-cancer (human germline CRISPR-Cas 9 knockout DNA repair genes) mutational signature databases. These analyses suggest inaccurate mismatch during initiation excision processes, along damage replication errors, major sources SNVs. Our findings information for understanding critical role their genesis.

Language: Английский

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