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Journal of Theoretical Biology Sep 2023The cost of germline maintenance gives rise to a trade-off between lowering the deleterious mutation rate and investing in life history functions. Therefore, life...
The cost of germline maintenance gives rise to a trade-off between lowering the deleterious mutation rate and investing in life history functions. Therefore, life history and the mutation rate coevolve, but this coevolution is not well understood. We develop a mathematical model to analyse the evolution of resource allocation traits, which simultaneously affect life history and the deleterious mutation rate. First, we show that the invasion fitness of such resource allocation traits can be approximated by the basic reproductive number of the least-loaded class; the expected lifetime production of offspring without deleterious mutations born to individuals without deleterious mutations. Second, we apply the model to investigate (i) the coevolution of reproductive effort and germline maintenance and (ii) the coevolution of age-at-maturity and germline maintenance. This analysis provides two resource allocation predictions when exposure to environmental mutagens is higher. First, selection favours higher allocation to germline maintenance, even if it comes at the expense of life history functions, and leads to a shift in allocation towards reproduction rather than survival. Second, life histories tend to be faster, characterised by individuals with shorter lifespans and smaller body sizes at maturity. Our results suggest that mutation accumulation via the cost of germline maintenance can be a major force shaping life-history traits.
Topics: Humans; Mutation Rate; Basic Reproduction Number; Body Size; Life History Traits; Mutation Accumulation
PubMed: 37598761
DOI: 10.1016/j.jtbi.2023.111598 -
Signal Transduction and Targeted Therapy Aug 2022
Topics: Longevity; Mutation Rate
PubMed: 35961971
DOI: 10.1038/s41392-022-01122-8 -
The New Phytologist Mar 2023Genetic mutations provide the heritable material for plant adaptation to their environments. At the same time, the environment can affect the mutation rate across plant... (Review)
Review
Genetic mutations provide the heritable material for plant adaptation to their environments. At the same time, the environment can affect the mutation rate across plant genomes. However, the extent to which environmental plasticity in mutation rates can facilitate or hinder adaptation remains a longstanding and unresolved question. Emerging discoveries of mechanisms affecting mutation rate variability provide opportunities to consider this question in a new light. Links between chromatin states, transposable elements, and DNA repair suggest cases of adaptive mutation rate plasticity could occur. Yet, numerous evolutionary and biological forces are expected to limit the impact of any such mutation rate plasticity on adaptive evolution. Persistent uncertainty about the significance of mutation rate plasticity on adaptation motivates new experimental and theoretical research relevant to understanding plant responses in changing environments.
Topics: Mutation Rate; Biological Evolution; Adaptation, Physiological; Mutation; Genome, Plant; Plants
PubMed: 36444532
DOI: 10.1111/nph.18640 -
Cells Jan 2024Driver mutations are considered the cornerstone of cancer initiation. They are defined as mutations that convey a competitive fitness advantage, and hence, their... (Review)
Review
Driver mutations are considered the cornerstone of cancer initiation. They are defined as mutations that convey a competitive fitness advantage, and hence, their mutation frequency in premalignant tissue is expected to exceed the basal mutation rate. In old terms, that translates to "the survival of the fittest" and implies that a selective process underlies the frequency of cancer driver mutations. In that sense, each tissue is its own niche that creates a molecular selective pressure that may favor the propagation of a mutation or not. At the heart of this stands one of the biggest riddles in cancer biology: the tissue-predisposition to cancer driver mutations. The frequency of cancer driver mutations among tissues is non-uniform: for instance, mutations in are particularly frequent in colorectal cancer, and 99% of chronic myeloid leukemia patients harbor the driver fusion mutation, which is rarely found in solid tumors. Here, we provide a mechanistic framework that aims to explain how tissue-specific features, ranging from epigenetic underpinnings to the expression of viral transposable elements, establish a molecular basis for selecting cancer driver mutations in a tissue-specific manner.
Topics: Humans; Precancerous Conditions; Disease Susceptibility; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mutation; Mutation Rate
PubMed: 38247798
DOI: 10.3390/cells13020106 -
Current Opinion in Genetics &... Jun 2020Germline mutations are the source of all heritable variation. In the past few years, whole genome sequencing has allowed direct and comprehensive surveys of mutation... (Review)
Review
Germline mutations are the source of all heritable variation. In the past few years, whole genome sequencing has allowed direct and comprehensive surveys of mutation patterns in humans and other species. These studies have documented substantial variation in both mutation rates and spectra across primates, the causes of which remain unclear. Here, we review what is currently known about mutation rates in primates, highlight the factors proposed to explain the variation across species, and discuss some implications of these findings on our understanding of the chronology of primate evolution and the process of mutagenesis.
Topics: Animals; Biological Evolution; Genome; Genomics; Mutation; Mutation Rate; Primates
PubMed: 32634682
DOI: 10.1016/j.gde.2020.05.028 -
Journal of Molecular Evolution Jun 2023Loss of heterozygosity (LOH) is a mitotic recombination event that converts heterozygous loci to homozygous loci. This mutation event is widespread in organisms that... (Review)
Review
Loss of heterozygosity (LOH) is a mitotic recombination event that converts heterozygous loci to homozygous loci. This mutation event is widespread in organisms that have asexual reproduction like budding yeasts, and is also an important and frequent mutation event in tumorigenesis. Mutation accumulation studies have demonstrated that LOH occurs at a rate higher than the point mutation rate, and can impact large portions of the genome. Laboratory evolution experiments of heterozygous yeasts have revealed that LOH often unmasks beneficial recessive alleles that can confer large fitness advantages. Here, I highlight advances in understanding dominance, fitness, and phenotypes in laboratory evolved heterozygous yeast strains. I discuss best practices for detecting LOH in intraspecific and interspecific evolved clones and populations. Utilizing heterozygous strain backgrounds in laboratory evolution experiments offers an opportunity to advance our understanding of this important mutation type in shaping adaptation and genome evolution in wild, domesticated, and clinical populations.
Topics: Saccharomyces cerevisiae; Mutation; Loss of Heterozygosity; Mutation Rate; Genome
PubMed: 36752826
DOI: 10.1007/s00239-022-10088-8 -
DNA Repair Sep 2019Cancer genome sequencing has revealed that somatic mutation rates vary substantially across the human genome and at scales from megabase-sized domains to individual... (Review)
Review
Cancer genome sequencing has revealed that somatic mutation rates vary substantially across the human genome and at scales from megabase-sized domains to individual nucleotides. Here we review recent work that has both revealed the major mutation biases that operate across the genome and the molecular mechanisms that cause them. The default mutation rate landscape in mammalian genomes results in active genes having low mutation rates because of a combination of factors that increase DNA repair: early DNA replication, transcription, active chromatin modifications and accessible chromatin. Therefore, either an increase in the global mutation rate or a redistribution of mutations from inactive to active DNA can increase the rate at which consequential mutations are acquired in active genes. Several environmental carcinogens and intrinsic mechanisms operating in tumor cells likely cause cancer by this second mechanism: by specifically increasing the mutation rate in active regions of the genome.
Topics: Chromatin; DNA; DNA Repair; Genome, Human; Humans; Mutation Rate; Neoplasms
PubMed: 31307927
DOI: 10.1016/j.dnarep.2019.102647 -
Nature Mar 2023The germline mutation rate determines the pace of genome evolution and is an evolving parameter itself. However, little is known about what determines its evolution, as...
The germline mutation rate determines the pace of genome evolution and is an evolving parameter itself. However, little is known about what determines its evolution, as most studies of mutation rates have focused on single species with different methodologies. Here we quantify germline mutation rates across vertebrates by sequencing and comparing the high-coverage genomes of 151 parent-offspring trios from 68 species of mammals, fishes, birds and reptiles. We show that the per-generation mutation rate varies among species by a factor of 40, with mutation rates being higher for males than for females in mammals and birds, but not in reptiles and fishes. The generation time, age at maturity and species-level fecundity are the key life-history traits affecting this variation among species. Furthermore, species with higher long-term effective population sizes tend to have lower mutation rates per generation, providing support for the drift barrier hypothesis. The exceptionally high yearly mutation rates of domesticated animals, which have been continually selected on fecundity traits including shorter generation times, further support the importance of generation time in the evolution of mutation rates. Overall, our comparative analysis of pedigree-based mutation rates provides ecological insights on the mutation rate evolution in vertebrates.
Topics: Animals; Female; Male; Birds; Evolution, Molecular; Fishes; Germ-Line Mutation; Mammals; Mutation Rate; Reptiles; Vertebrates
PubMed: 36859541
DOI: 10.1038/s41586-023-05752-y -
Genes Mar 2023Mutation rate is a crucial parameter in evolutionary genetics. However, the mutation rate of most species as well as the extent to which the environment can alter the...
Mutation rate is a crucial parameter in evolutionary genetics. However, the mutation rate of most species as well as the extent to which the environment can alter the genome of multicellular organisms remain poorly understood. Here, we used parents-progeny sequencing to investigate the mutation rate and spectrum of the domestic silkworm () among normal and two temperature stress conditions (32 °C and 0 °C). The rate of single-nucleotide mutations in the normal temperature rearing condition was 0.41 × 10 (95% confidence interval, 0.33 × 10-0.49 × 10) per site per generation, which was up to 1.5-fold higher than in four previously studied insects. Moreover, the mutation rates of the silkworm under the stresses are significantly higher than in normal conditions. Furthermore, the mutation rate varies less in gene regions under normal and temperature stresses. Together, these findings expand the known diversity of the mutation rate among eukaryotes but also have implications for evolutionary analysis that assumes a constant mutation rate among species and environments.
Topics: Animals; Bombyx; Temperature; Mutation Rate; Insecta; Genome
PubMed: 36980921
DOI: 10.3390/genes14030649 -
Molecular Biology and Evolution Aug 2021De novo mutations are central for evolution, since they provide the raw material for natural selection by regenerating genetic variation. However, studying de novo...
De novo mutations are central for evolution, since they provide the raw material for natural selection by regenerating genetic variation. However, studying de novo mutations is challenging and is generally restricted to model species, so we have a limited understanding of the evolution of the mutation rate and spectrum between closely related species. Here, we present a mutation accumulation (MA) experiment to study de novo mutation in the unicellular green alga Chlamydomonas incerta and perform comparative analyses with its closest known relative, Chlamydomonas reinhardtii. Using whole-genome sequencing data, we estimate that the median single nucleotide mutation (SNM) rate in C. incerta is μ = 7.6 × 10-10, and is highly variable between MA lines, ranging from μ = 0.35 × 10-10 to μ = 131.7 × 10-10. The SNM rate is strongly positively correlated with the mutation rate for insertions and deletions between lines (r > 0.97). We infer that the genomic factors associated with variation in the mutation rate are similar to those in C. reinhardtii, allowing for cross-prediction between species. Among these genomic factors, sequence context and complexity are more important than GC content. With the exception of a remarkably high C→T bias, the SNM spectrum differs markedly between the two Chlamydomonas species. Our results suggest that similar genomic and biological characteristics may result in a similar mutation rate in the two species, whereas the SNM spectrum has more freedom to diverge.
Topics: Base Composition; Chlamydomonas; Chlamydomonas reinhardtii; Mutation; Mutation Accumulation; Mutation Rate
PubMed: 33950243
DOI: 10.1093/molbev/msab140