Low mutation rate but high male-bias in the germline of a short-lived opossum DOI Open Access
Yadira Peña-García, Richard J. Wang, Muthuswamy Raveendran

и другие.

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

Опубликована: Дек. 10, 2024

Abstract Age and sex have been found to be important determinants of the mutation rate per generation in mammals, but mechanisms underlying these factors are still unclear. One approach distinguishing between alternative is study species that reproduce at very young ages, as competing hypotheses make different predictions about patterns organisms. Here, we germline gray short-tailed opossum, Monodelphis domestica, a laboratory model becomes reproductively mature less than six months age. Whole-genome sequencing 22 trios reveals lowest mammals thus far (0.26 × 10-8 base pair an average parental age 313 days), which expected given their early reproduction. We also examine spectrum find fewer mutations CpG sites opossums humans, consistent with lower content opossum genome. observe two-thirds inherited from male parent opossums, slightly degree bias observed organisms much older ages. Nevertheless, reproduction suggests ongoing spermatogonial divisions males after puberty not primary driver bias. These findings contribute growing body evidence differences female may arise other cell division post-puberty. Article Summary This investigates marsupial reproductive maturity. By families, report recorded typical add challenges traditional view continuing male-biased mutations. Instead, mechanisms, such DNA repair, influence sex-specific rates.

Язык: Английский

Unprecedented female mutation bias in the aye-aye, a highly unusual lemur from Madagascar DOI Creative Commons
Richard J. Wang, Yadira Peña-García, Muthuswamy Raveendran

и другие.

PLoS Biology, Год журнала: 2025, Номер 23(2), С. e3003015 - e3003015

Опубликована: Фев. 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.

Язык: Английский

Процитировано

1
Characterizing the Rates and Patterns of De Novo Germline Mutations in the Aye-Aye (Daubentonia madagascariensis) DOI Creative Commons
Cyril J. Versoza, Erin E. Ehmke, Jeffrey D. Jensen

и другие.

Molecular Biology and Evolution, Год журнала: 2025, Номер 42(3)

Опубликована: Март 1, 2025

Given the many levels of biological variation in mutation rates observed to date primates-spanning from species individuals genomic regions-future steps our understanding rate evolution will not only be aided by a greater breadth coverage across primate clade but also depth as afforded an evaluation multiple trios within individual species. In order help bridge these gaps, we here present analysis representing one most basal splits on tree (aye-ayes), combining whole-genome sequencing seven parent-offspring three-generation pedigree with novel computational pipeline that takes advantage recently developed pan-genome graphs, thereby circumventing application (highly subjective) quality metrics has previously been shown result notable differences detection de novo mutations and ultimately estimates rates. This deep sampling enabled both detailed picture parental age effects sex dependency rates, which compare studied primates, provided unique insights into nature genetic endangered primates planet.

Язык: Английский

Процитировано

1
Sperm from infertile, oligozoospermic men have elevated mutation rates DOI Creative Commons
Jason Kunisaki, Michael E. Goldberg,

Suchita Lulla

и другие.

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

Опубликована: Авг. 22, 2024

Abstract Male infertility is associated with elevated rates of aneuploidy and DNA breaks in spermatozoa germline precursors. This common condition not well understood poor individual familial somatic health relative to fertile men. To further understand the extent source genome instability, we used error-corrected duplex sequencing test whether impaired spermatogenesis relatively poorer oligozoospermic men are linked single nucleotide de novo mutation frequencies their sperm blood, respectively. We observed a significant 1.34 2.01-fold increase age-adjusted infertile, Conversely, consistently blood were found. Gain-of-function mutations clonal Mendelian disorders accumulate age at similar rate normozoospermic These results implicate hypermutation as hallmark feature oligozoospermia point age-independent processes affecting spermatogonial stem cell biology that may underlie spermatogenic impairment before after puberty. Our findings also underscore importance investigating tissue-specific mechanisms driving association between reduced reproductive infertile

Язык: Английский

Процитировано

4
Paternal age, de novo mutations, and offspring health? New directions for an ageing problem DOI Creative Commons
R. John Aitken

Human Reproduction, Год журнала: 2024, Номер 39(12), С. 2645 - 2654

Опубликована: Окт. 3, 2024

This Directions article examines the mechanisms by which a father's age impacts health and wellbeing of his children. Such are significant include adverse birth outcomes, dominant genetic conditions, neuropsychiatric disorders, variety congenital developmental defects. As well as age, wide environmental lifestyle factors also known to impact offspring via changes mediated male germ line. picture dynamic line responsive range intrinsic extrinsic contrasts with results trio studies indicating that incidence mutations in is low exhibits linear, monotonic increase paternal (∼two new per year). While traditional explanation for this pattern mutation has been metronomic plod replication errors, an alternative model pivots around 'faulty male' hypothesis. According concept, integrity can be dynamically impacted other factors, it aberrant repair such damage drives mutagenesis. Fortunately, DNA proofreading during spermatogenesis extremely effective these mutant cells either repaired or deleted apoptosis/ferroptosis. There appear only two escape apoptotic fate: (i) if acquire enhancing proliferation suppressing apoptosis, permits their clonal expansion (selfish selection hypothesis) (ii) genetically damaged spermatozoon manages fertilize oocyte, then fixes (or epimutation) result defective (oocyte collusion hypothesis). Exploration proposed should not help us better understand aetiology effects but inform potential avenues remediation.

Язык: Английский

Процитировано

3
Estimates of the Mutation Rate per Year Can Explain Why the Molecular Clock Depends on Generation Time DOI Creative Commons

Loveday E Lewin,

Adam Eyre‐Walker

Molecular Biology and Evolution, Год журнала: 2025, Номер 42(4)

Опубликована: Март 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.

Язык: Английский

Процитировано

0
Characterization and distribution of de novo mutations in the zebra finch DOI Creative Commons
Xixi Liang, Shuai Yang, Daiping Wang

и другие.

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Окт. 2, 2024

Язык: Английский

Процитировано

1
“Evolution of the mutation spectrum across a mammalian phylogeny” DOI Creative Commons
Annabel C. Beichman, Jacqueline A. Robinson, Meixi Lin

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июнь 1, 2023

Little is known about how the spectrum and etiology of germline mutagenesis might vary among mammalian species. To shed light on this mystery, we quantify variation in mutational sequence context biases using polymorphism data from thirteen species mice, apes, bears, wolves, cetaceans. After normalizing mutation for reference genome accessibility

Язык: Английский

Процитировано

3
A modelling of complex trait phenotypic variance determinants DOI Creative Commons
Shobbir Hussain

PNAS Nexus, Год журнала: 2024, Номер 3(11)

Опубликована: Окт. 18, 2024

Studies have now shown that the heritability of some complex traits, such as human height, can be virtually fully captured via potential use sufficiently powered approaches characterize associated collective common- and rare-variant additive genetic architecture. However, for other including disease full recovery narrow sense would still likely fall far short respective estimates yielded from pedigree-based analyses twin studies. Here, it is proposed traits could also involve additional types relevant architecture underlying mechanism, interaction somatic variants with heritable may represent an underappreciated component. The theoretical model suggested predicts are systematically inflated by studies, instead a significant proportion phenotypic variances explained specialized genotype-by-environment interaction.

Язык: Английский

Процитировано

0
Low mutation rate but high male-bias in the germline of a short-lived opossum DOI Open Access
Yadira Peña-García, Richard J. Wang, Muthuswamy Raveendran

и другие.

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

Опубликована: Дек. 10, 2024

Abstract Age and sex have been found to be important determinants of the mutation rate per generation in mammals, but mechanisms underlying these factors are still unclear. One approach distinguishing between alternative is study species that reproduce at very young ages, as competing hypotheses make different predictions about patterns organisms. Here, we germline gray short-tailed opossum, Monodelphis domestica, a laboratory model becomes reproductively mature less than six months age. Whole-genome sequencing 22 trios reveals lowest mammals thus far (0.26 × 10-8 base pair an average parental age 313 days), which expected given their early reproduction. We also examine spectrum find fewer mutations CpG sites opossums humans, consistent with lower content opossum genome. observe two-thirds inherited from male parent opossums, slightly degree bias observed organisms much older ages. Nevertheless, reproduction suggests ongoing spermatogonial divisions males after puberty not primary driver bias. These findings contribute growing body evidence differences female may arise other cell division post-puberty. Article Summary This investigates marsupial reproductive maturity. By families, report recorded typical add challenges traditional view continuing male-biased mutations. Instead, mechanisms, such DNA repair, influence sex-specific rates.

Язык: Английский

Процитировано

0