Estimation of the species-specific mutation rates at the DRB1 locus in humans and chimpanzee

AbstractMutation rates vary between species across several orders of magnitude, with larger organisms having the highest per-generation mutation rates. Hypotheses for this pattern typically invoke physiological or population-genetic constraints imposed on the molecular machinery preventing mutations1. However, continuing germline cell division in multicellular eukaryotes means that organisms with longer generation times and of larger size will leave more mutations to their offspring simply as a by-product of their increased lifespan2,3. Here, we deeply sequence the genomes of 30 owl monkeys (Aotus nancymaae) from 6 multi-generation pedigrees to demonstrate that paternal age is the major factor determining the number of de novo mutations in this species. We find that owl monkeys have an average mutation rate of 0.81 × 10−8 per site per generation, roughly 32% lower than the estimate in humans. Based on a simple model of reproductive longevity that does not require any changes to the mutational machinery, we show that this is the expected mutation rate in owl monkeys. We further demonstrate that our model predicts species-specific mutation rates in other primates, including study-specific mutation rates in humans based on the average paternal age. Our results suggest that variation in life history traits alone can explain variation in the per-generation mutation rate among primates, and perhaps among a wide range of multicellular organisms.

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Sex-Specific Mutation Rates in Salmonid Fish

Journal of Molecular Evolution ◽

10.1007/s00239-002-2416-z ◽

2003 ◽

Vol 56 (4) ◽

pp. 458-463 ◽

Cited By ~ 29

Author(s):

Hans Ellegren ◽

Anna-Karin Fridolfsson

Keyword(s):

Salmonid Fish ◽

Mutation Rates ◽

Specific Mutation

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Loss of Heterozygosity and Base Mutation Rates Vary Among Saccharomyces cerevisiae Hybrid Strains

G3 Genes|Genome|Genetics ◽

10.1534/g3.120.401551 ◽

2020 ◽

Vol 10 (9) ◽

pp. 3309-3319 ◽

Cited By ~ 2

Author(s):

Ajith V Pankajam ◽

Suman Dash ◽

Asma Saifudeen ◽

Abhishek Dutta ◽

Koodali T Nishant

Keyword(s):

Saccharomyces Cerevisiae ◽

Loss Of Heterozygosity ◽

Mutation Rates ◽

Single Nucleotide ◽

Single Nucleotide Mutation ◽

Genome Wide ◽

Nucleotide Mutation ◽

Specific Variation ◽

Chromosomal Changes ◽

Species Specific

Abstract A growing body of evidence suggests that mutation rates exhibit intra-species specific variation. We estimated genome-wide loss of heterozygosity (LOH), gross chromosomal changes, and single nucleotide mutation rates to determine intra-species specific differences in hybrid and homozygous strains of Saccharomyces cerevisiae. The mutation accumulation lines of the S. cerevisiae hybrid backgrounds - S288c/YJM789 (S/Y) and S288c/RM11-1a (S/R) were analyzed along with the homozygous diploids RM11, S288c, and YJM145. LOH was extensive in both S/Y and S/R hybrid backgrounds. The S/Y background also showed longer LOH tracts, gross chromosomal changes, and aneuploidy. Short copy number aberrations were observed in the S/R background. LOH data from the S/Y and S/R hybrids were used to construct a LOH map for S288c to identify hotspots. Further, we observe up to a sixfold difference in single nucleotide mutation rates among the S. cerevisiae S/Y and S/R genetic backgrounds. Our results demonstrate LOH is common during mitotic divisions in S. cerevisiae hybrids and also highlight genome-wide differences in LOH patterns and rates of single nucleotide mutations between commonly used S. cerevisiae hybrid genetic backgrounds.

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Great ape mutation spectra vary across the phylogeny and the genome due to distinct mutational processes that evolve at different rates

10.1101/805598 ◽

2019 ◽

Cited By ~ 1

Author(s):

Michael E. Goldberg ◽

Kelley Harris

Keyword(s):

Replication Timing ◽

Mutation Rates ◽

Great Ape ◽

Mutational Signatures ◽

Clock Model ◽

Cis Acting ◽

Molecular Clock Model ◽

Species Specific ◽

Mutation Spectra ◽

Mutational Processes

ABSTRACTRecent studies of hominoid variation have shown that mutation rates and spectra can evolve rapidly, contradicting the fixed molecular clock model. The relative mutation rates of three-base-pair motifs differ significantly among great ape species, suggesting the action of unknown modifiers of DNA replication fidelity. To illuminate the footprints of these hypothetical mutators, we measured mutation spectra of several functional compartments (such as late-replicating regions) that are likely targeted by localized mutational processes. Using genetic diversity from 88 great apes, we find that compartment-specific mutational signatures appear largely conserved between species. These signatures layer with species-specific signatures to create rich mutational portraits: for example, late-replicating regions in gorillas contain an identifiable mixture of a replication timing signature and a gorilla-specific signature. Our results suggest that cis-acting mutational modifiers are highly conserved between species and transacting modifiers are driving rapid mutation spectrum evolution.

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Bayesian co-estimation of selfing rate and locus-specific mutation rates for a partially selfing population

10.1101/020537 ◽

2015 ◽

Author(s):

Benjamin D Redelings ◽

Seiji Kumagai ◽

Liuyang Wang ◽

Andrey Tatarenkov ◽

Ann K. Sakai ◽

...

Keyword(s):

Mating System ◽

Dirichlet Process ◽

Mutation Rates ◽

Common Mutation ◽

Dirichlet Process Prior ◽

Coalescence Model ◽

Specific Mutation ◽

Sampling Formula ◽

Self Fertilization ◽

Infinite Alleles Model

We present a Bayesian method for characterizing the mating system of populations reproducing through a mixture of self-fertilization and random outcrossing. Our method uses patterns of genetic variation across the genome as a basis for inference about pure hermaphroditism, androdioecy, and gynodioecy. We extend the standard coalescence model to accommodate these mating systems, accounting explicitly for multilocus identity disequilibrium, inbreeding depression, and variation in fertility among mating types. We incorporate the Ewens Sampling Formula (ESF) under the infinite-alleles model of mutation to obtain a novel expression for the likelihood of mating system parameters. Our Markov chain Monte Carlo (MCMC) algorithm assigns locus-specific mutation rates, drawn from a common mutation rate distribution that is itself estimated from the data using a Dirichlet Process Prior model. Among the parameters jointly inferred are the population-wide rate of self-fertilization, locus-specific mutation rates, and the number of generations since the most recent outcrossing event for each sampled individual.

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DNA Variation in a 5-Mb Region of the X Chromosome and Estimates of Sex-Specific/Type-Specific Mutation Rates

The American Journal of Human Genetics ◽

10.1086/302250 ◽

1999 ◽

Vol 64 (2) ◽

pp. 508-517 ◽

Cited By ~ 18

Author(s):

Theodore Anagnostopoulos ◽

Peter M. Green ◽

Gabriella Rowley ◽

Cathryn M. Lewis ◽

Francesco Giannelli

Keyword(s):

X Chromosome ◽

Mutation Rates ◽

Dna Variation ◽

Specific Mutation

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Maximum-Likelihood Estimation of Site-Specific Mutation Rates in Human Mitochondrial DNA From Partial Phylogenetic Classification

Genetics ◽

10.1534/genetics.108.091116 ◽

2008 ◽

Vol 180 (3) ◽

pp. 1511-1524 ◽

Cited By ~ 12

Author(s):

Saharon Rosset ◽

R. Spencer Wells ◽

David F. Soria-Hernanz ◽

Chris Tyler-Smith ◽

Ajay K. Royyuru ◽

...

Keyword(s):

Mitochondrial Dna ◽

Maximum Likelihood ◽

Maximum Likelihood Estimation ◽

Likelihood Estimation ◽

Mutation Rates ◽

Site Specific ◽

Human Mitochondrial Dna ◽

Specific Mutation ◽

Phylogenetic Classification

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Temperature-dependence of spontaneous mutation rates

10.1101/2020.11.03.366807 ◽

2020 ◽

Author(s):

Ann-Marie Waldvogel ◽

Markus Pfenninger

Keyword(s):

Genetic Variation ◽

Null Hypothesis ◽

Spontaneous Mutation ◽

Empirical Support ◽

Mutation Rates ◽

Temperature Extremes ◽

Whole Genome ◽

Direct Impact ◽

Species Specific ◽

Dependent Processes

Mutation is the source of genetic variation and the fundament of evolution. At the interphase of ecology and evolution, temperature has long been suggested to have a direct impact on realised spontaneous mutation rates. The question is whether mutation rates can be a species-specific constant under variable environmental conditions, such as variation of the ambient temperature. By combining mutation accumulation with whole genome sequencing in a multicellular organism, we provide empirical support to reject this null hypothesis. Instead mutation rates depend on temperature in a U-shaped manner with increasing rates towards both temperature extremes. This relation has important implications for mutation dependent processes in molecular evolution, processes shaping the evolution of mutation rates and even the evolution of biodiversity as such.

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