High germline mutation rates, but not extreme population outbreaks, influence genetic diversity in a keystone coral predator

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(2), P. e1011129 - e1011129

Published: Feb. 12, 2024

Lewontin's paradox, the observation that levels of genetic diversity (π) do not scale linearly with census population size (Nc) variation, is an evolutionary conundrum. The most extreme mismatches between π and Nc are found for highly abundant marine invertebrates. Yet, influences new mutations on relative to extrinsic processes such as fluctuations unknown. Here, we provide first germline mutation rate (μ) estimate a invertebrate in corallivorous crown-of-thorns sea stars (Acanthaster cf. solaris). We use high-coverage whole-genome sequencing 14 parent-offspring trios alongside empirical estimates Australia's Great Barrier Reef jointly examine determinants populations undergoing fluctuations. A. solaris mean μ was 9.13 x 10-09 per-site per-generation (95% CI: 6.51 1.18 10-08), exceeding other invertebrates showing greater concordance vertebrate rates. Lower-than-expected Ne (~70,000-180,000) low Ne/Nc values (0.0047-0.048) indicated weak outbreaks long-term π. Our findings consistent elevated evolving response reduced generation time length, important implications explaining high mutational loads taxa.

Language: Английский

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The diagnostic relevance of mesenteric lymph node biopsy in small intestinal lymphoma in cats

Journal of Veterinary Internal Medicine, Journal Year: 2024, Volume and Issue: 38(4), P. 2316 - 2323

Published: June 10, 2024

Abstract Background Regional lymph nodes are frequently sampled in cats with suspected intestinal lymphoma; however, their diagnostic value has not been explored. Objectives To investigate whether histologic and immunohistochemical analysis of mesenteric correlates the diagnosis lymphoma cats. Animals One hundred 2 client‐owned diagnosed lymphoma. Methods Retrospective study. The inclusion criteria required a full‐thickness biopsy small intestine concurrent excision nodes. Histologic immunophenotypic analyses were performed on biopsies corresponding Selected nodal samples reactive underwent clonality testing. Results Transmural T‐cell lymphomas, encompassing large cell types, predominant (64 cases, 62.7%), B‐cell lymphomas being more transmural (68.8%) than mucosal (31.2%). Among all examined, 44 (43.1%; 95% CI: 33.9%‐52.8%) exhibited neoplastic infiltration. cases lymphoma, 51 out 72 (70.8%; 59.4%‐80.1%) showed no involvement. Clonality results correctly identified 19/30 (63.3%; 45.5%‐78.2%) Concerns raised regarding clonal identification remaining potential misdiagnoses based phenotypic characteristics. Conclusion Clinical Importance study underscores drawbacks relying solely for diagnosing cats, particularly subtypes. It emphasizes importance assessing infiltration recommends caution when utilizing histologic, evaluations lymphomas. Despite limitations, this research highlights need comprehensive strategies

Language: Английский

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Quantifying the effects of computational filter criteria on the accurate identification of de novo mutations at varying levels of sequencing coverage

Heredity, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Language: Английский

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Estimates of the Mutation Rate per Year Can Explain Why the Molecular Clock Depends on Generation Time

Molecular Biology and Evolution, Journal Year: 2025, Volume and Issue: 42(4)

Published: March 25, 2025

Abstract Rates of molecular evolution are known to vary across species, often deviating from the classical expectation a strict clock. In many cases, rate has been found correlate generation time, an effect that could be explained if species with shorter times have higher mutation rates per year. We investigate this hypothesis using direct estimates for 133 eukaryotic diverse taxonomic groups. Using phylogenetic comparative approach, we find strong negative correlation between year and consistent all Our results provide simple explanation why time plays pivotal role in driving eukaryotes.

Language: Английский

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Population size interacts with reproductive longevity to shape the germline mutation rate

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(21)

Published: May 20, 2025

Mutation rates vary across the tree of life by many orders magnitude, with fewer mutations occurring each generation in species that reproduce quickly and maintain large effective population sizes. A compelling explanation is sizes facilitate selection against weakly deleterious “mutator alleles” such as variants modulate cell division or interfere molecular efficacy DNA repair. However, while fidelity a single largely determines microorganisms’ mutation rates, relationship rate to determinants damage repair more complex multicellular long times. Since generations leave time for accrue generation, we posit likely amplifies fitness consequences any agent defect creates extra spermatogonia oocytes. This leads counterintuitive prediction highest germline per are also most mechanisms avoiding repairing their reproductive cells. Consistent this, show cells inversely correlated time; contrast, number occur during prepuberty development trends upward increases. Our results parallel recent findings longest-lived have lowest adult somatic tissues, potentially due keep lifetime load below harmful threshold.

Language: Английский

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De Novo Mutation Rates in Sticklebacks

Molecular Biology and Evolution, Journal Year: 2023, Volume and Issue: 40(9)

Published: Aug. 30, 2023

Mutation rate is a fundamental parameter in population genetics. Apart from being an important scaling for demographic and phylogenetic inference, it allows one to understand at what new genetic diversity generated the expected level of equilibrium. However, except well-established model organisms, accurate estimates de novo mutation rates are available very limited number organisms wild. We estimated (µ) two marine populations nine-spined stickleback (Pungitius pungitius) with aid several 2- 3-generational family pedigrees, deep (>50×) whole-genome resequences high-quality reference genome. After stringent filtering, we discovered 308 germline mutations 106 offspring translating µ = 4.83 × 10-9 4.29 per base generation populations, respectively. Up 20% were shared by full-sibs showing that parental mosaicism was relatively high. Since 3.1 times smaller than commonly used substitution rate, recalibration led substantial increase divergence between different species. Our should provide useful resource research focused on fish genetics sticklebacks particular.

Language: Английский

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Extensive Phylogenomic Discordance and the Complex Evolutionary History of the Neotropical Cat Genus Leopardus

Molecular Biology and Evolution, Journal Year: 2023, Volume and Issue: 40(12)

Published: Nov. 21, 2023

Even in the genomics era, phylogeny of Neotropical small felids comprised genus Leopardus remains contentious. We used whole-genome resequencing data to construct a time-calibrated consensus this group, quantify phylogenomic discordance, test for interspecies introgression, and assess patterns genetic diversity demographic history. infer that radiation started Early Pliocene as an initial speciation burst, followed by another its subgenus Oncifelis during Pleistocene. Our findings challenge long-held notion ocelot (Leopardus pardalis) margay (L. wiedii) are sister species instead indicate is most closely related enigmatic Andean cat jacobita), whose reported here first time. In addition, we found newly sampled tiger tigrinus pardinoides) population from Colombia associates with Central American cats oncilla). Genealogical discordance was largely attributable incomplete lineage sorting, yet augmented strong gene flow between ancestral branch Oncifelis, well Geoffroy's geoffroyi) southern guttulus). Contrasting trajectories have led disparate levels current genomic diversity, nearly tenfold difference heterozygosity ocelot, spanning entire range variability extant felids. analyses improved our understanding history felid radiation, highlight benefits inference embracing many heterogeneous signals scattered across genome.

Language: Английский

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Examining the Effects of Hibernation on Germline Mutation Rates in Grizzly Bears

Genome Biology and Evolution, Journal Year: 2022, Volume and Issue: 14(10)

Published: Sept. 29, 2022

Abstract A male mutation bias is observed across vertebrates, and, where data are available, this accompanied by increased per-generation rates with parental age. While continuing mitotic cell division in the germline post puberty has been proposed as major cellular mechanism underlying both patterns, little direct evidence for role found. Understanding evolution of rate among species requires that we identify molecular mechanisms change between species. Here, study an extended pedigree brown (grizzly) bear, Ursus arctos horribilis. Brown bears hibernate one-third year, a period during which spermatogenesis slows or stops altogether. The reduction predicted to lessen and lower However, using whole-genome sequencing, find highly similar expected non-hibernating We also carry out phylogenetic comparison substitution along lineage leading bear panda (a species) no slowing hibernator. Our results contribute accumulating suggests not determinant biases. provide quantitative basis improved estimates timing carnivore evolution.

Language: Английский

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Epistasis between mutator alleles contributes to germline mutation spectrum variability in laboratory mice

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

Published: July 20, 2023

Maintaining germline genome integrity is essential and enormously complex. Although many proteins are involved in DNA replication, proofreading, repair, mutator alleles have largely eluded detection mammals. replication repair often recognize sequence motifs or excise lesions at specific nucleotides. Thus, we might expect that the spectrum of de novo mutations - frequencies C>T, A>G, etc. will differ between genomes harbor either a wild-type allele. Previously, used quantitative trait locus mapping to discover candidate gene Mutyh increased C>A mutation rate family inbred mice known as BXDs (Sasani et al., 2022, Ashbrook 2021). In this study developed new method detect associated with variation applied it data from BXDs. We discovered an additional on chromosome 6 overlaps Ogg1, glycosylase same base-excision network (David 2007). Its effect depends presence allele near Mutyh, both loci greater numbers than those alone. Our methods for analyzing spectra reveal evidence epistasis may be applicable humans other model organisms.

Language: Английский

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Evolution of the Mutation Spectrum Across a Mammalian Phylogeny

Molecular Biology and Evolution, Journal Year: 2023, Volume and Issue: 40(10)

Published: Sept. 26, 2023

Abstract Although evolutionary biologists have long theorized that variation in DNA repair efficacy might explain some of the diversity lifespan and cancer incidence across species, we little data on variability normal germline mutagenesis outside humans. Here, shed light spectrum etiology mammals by quantifying mutational sequence context biases using polymorphism from thirteen species mice, apes, bears, wolves, cetaceans. After normalizing mutation for reference genome accessibility k-mer content, use Mantel test to deduce divergence is highly correlated with genetic between whereas life history traits like reproductive age are weaker predictors divergence. Potential bioinformatic confounders only weakly related a small set features. We find clock-like signatures previously inferred human cancers cannot phylogenetic signal exhibited mammalian spectrum, despite ability these fit each species’ 3-mer high cosine similarity. In contrast, parental aging de novo appear much 1-mer spectrum's combination novel signature. posit future models purporting need capture fact more closely similar spectra; model fits marginal similarity not guaranteed this hierarchy among species.

Language: Английский

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