Pedigree Derived Mutation Rate Across the Entire Mitochondrial Genome of the Norfolk Island Population

Abstract Estimates of mutation rates for various regions of the mitochondrial genome (mtGenome) vary widely, depending on whether they are inferred using a phylogenetic approach or obtained directly from pedigrees. Traditionally, only the control region, or small portions of the coding region have been targeted for analysis due to the cost and effort required to produce whole mtGenome Sanger profiles. Here, we report one of the first pedigree derived mutation rates for the entire human mtGenome. The entire mtGenome from 225 individuals originating from Norfolk Island was analysed to estimate the population mutation rate and compared against published mutation rates. These individuals were from 45 maternal lineages spanning 345 generational events. Mutation rates for various portions of the mtGenome were calculated. Nine mutations (including two transitions and seven cases of heteroplasmy) were observed, resulting in a rate of 0.063 mutations/site/million years (95% confidence interval: 0.033 – 0.118). These mutation rates are approximately 17 times higher than estimates derived from phylogenetic analysis with heteroplasmy detected in 13 samples (n=225, 5.8% individuals). Providing one of the first pedigree derived estimates for the entire mtGenome, this study provides a better understanding of mtGenome evolution and has relevance to many research fields, including medicine, anthropology and forensics.

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The Complete Mitochondrial Genome of the New Zealand Parasitic Blowfly Lucilia sericata (Insecta: Diptera: Calliphoridae)

10.20944/preprints202010.0601.v1 ◽

2020 ◽

Author(s):

Nikola Palevich

Keyword(s):

Phylogenetic Analysis ◽

New Zealand ◽

Mitochondrial Genome ◽

Complete Mitochondrial Genome ◽

Lucilia Sericata ◽

Coding Region ◽

Protein Coding ◽

Next Generation Sequencing Technology ◽

Monophyletic Cluster ◽

Green Bottle

In the present study, the complete mitochondrial genome of the New Zealand parasitic blowfly Lucilia sericata (green bottle blowfly) field strain NZ_LucSer_NP was generated using next-generation sequencing technology. The length of complete the mitochondrial genome is 15,938 bp, with 39.4% A, 13.0% C, 9.3% G, and 38.2% T nucleotide distribution. The complete mitochondrial genome consists of 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, and a and a 1,124 bp non-coding region, similar to most metazoan mitochondrial genomes. Phylogenetic analysis showed that L. sericata NZ_LucSer_NP forms a monophyletic cluster with the remaining six Lucilia species and the Calliphoridae are polyphyletic. This study provides the first complete mitochondrial genome sequence for a L. sericata blowfly species derived from New Zealand to facilitate species identification and phylogenetic analysis.

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Bedrock radioactivity influences the rate and spectrum of mutation

eLife ◽

10.7554/elife.56830 ◽

2020 ◽

Vol 9 ◽

Author(s):

Nathanaëlle Saclier ◽

Patrick Chardon ◽

Florian Malard ◽

Lara Konecny-Dupré ◽

David Eme ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Genome ◽

Oxidative Damage ◽

Mutation Rate ◽

Natural Radioactivity ◽

Mutation Rates ◽

Low Doses ◽

Positive Correlation ◽

Nuclear Mutation

All organisms on Earth are exposed to low doses of natural radioactivity but some habitats are more radioactive than others. Yet, documenting the influence of natural radioactivity on the evolution of biodiversity is challenging. Here, we addressed whether organisms living in naturally more radioactive habitats accumulate more mutations across generations using 14 species of waterlice living in subterranean habitats with contrasted levels of radioactivity. We found that the mitochondrial and nuclear mutation rates across a waterlouse species’ genome increased on average by 60% and 30%, respectively, when radioactivity increased by a factor of three. We also found a positive correlation between the level of radioactivity and the probability of G to T (and complementary C to A) mutations, a hallmark of oxidative stress. We conclude that even low doses of natural bedrock radioactivity influence the mutation rate possibly through the accumulation of oxidative damage, in particular in the mitochondrial genome.

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Sign of selection on mutation rate modifiers depends on population size

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1715996115 ◽

2018 ◽

Vol 115 (13) ◽

pp. 3422-3427 ◽

Cited By ~ 17

Author(s):

Yevgeniy Raynes ◽

C. Scott Wylie ◽

Paul D. Sniegowski ◽

Daniel M. Weinreich

Keyword(s):

Population Size ◽

Mutation Rate ◽

Genetic System ◽

Indirect Selection ◽

Mutation Rates ◽

Deleterious Mutations ◽

Fitness Effects ◽

Sign Inversion ◽

Large Populations ◽

The Cost

The influence of population size (N) on natural selection acting on alleles that affect fitness has been understood for almost a century. AsNdeclines, genetic drift overwhelms selection and alleles with direct fitness effects are rendered neutral. Often, however, alleles experience so-called indirect selection, meaning they affect not the fitness of an individual but the fitness distribution of its offspring. Some of the best-studied examples of indirect selection include alleles that modify aspects of the genetic system such as recombination and mutation rates. Here, we use analytics, simulations, and experimental populations ofSaccharomyces cerevisiaeto examine the influence ofNon indirect selection acting on alleles that increase the genomic mutation rate (mutators). Mutators experience indirect selection via genomic associations with beneficial and deleterious mutations they generate. We show that, asNdeclines, indirect selection driven by linked beneficial mutations is overpowered by drift before drift can neutralize the cost of the deleterious load. As a result, mutators transition from being favored by indirect selection in large populations to being disfavored asNdeclines. This surprising phenomenon of sign inversion in selective effect demonstrates that indirect selection on mutators exhibits a profound and qualitatively distinct dependence onN.

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Bedrock radioactivity influences the rate and spectrum of mutation

10.1101/2020.03.23.003616 ◽

2020 ◽

Author(s):

Nathanaëlle Saclier ◽

Patrick Chardon ◽

Florian Malard ◽

Lara Konecny-Dupré ◽

David Eme ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Genome ◽

Oxidative Damage ◽

Mutation Rate ◽

Natural Radioactivity ◽

Mutation Rates ◽

Low Doses ◽

Positive Correlation ◽

Nuclear Mutation

AbstractAll organisms on Earth are exposed to low doses of natural radioactivity but some habitats are more radioactive than others. Yet, documenting the influence of natural radioactivity on the evolution of biodiversity is challenging. Here, we addressed whether organisms living in naturally more radioactive habitats accumulate more mutations across generations using 14 species of waterlice living in subterranean habitats with contrasted levels of radioactivity. We found that the mitochondrial and nuclear mutation rates across a waterlouse species’ genome increased on average by 60 and 30%, respectively, when radioactivity increased by a factor of three. We also found a positive correlation between the level of radioactivity and the probability of G to T (and complementary C to A) mutations, a hallmark of oxidative stress. We conclude that even low doses of natural bedrock radioactivity influence the mutation rate through the likely accumulation of oxidative damage, in particular in the mitochondrial genome.

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Beneficial Mutations, Hitchhiking and the Evolution of Mutation Rates in Sexual Populations

Genetics ◽

10.1093/genetics/151.4.1621 ◽

1999 ◽

Vol 151 (4) ◽

pp. 1621-1631 ◽

Cited By ~ 6

Author(s):

Toby Johnson

Keyword(s):

Mutation Rate ◽

Indirect Selection ◽

Mutation Rates ◽

Deleterious Mutations ◽

Heritable Variation ◽

Asexual Population ◽

Beneficial Mutations ◽

Long Term Effect ◽

The Cost ◽

Substantial Change

Abstract Natural selection acts in three ways on heritable variation for mutation rates. A modifier allele that increases the mutation rate is (i) disfavored due to association with deleterious mutations, but is also favored due to (ii) association with beneficial mutations and (iii) the reduced costs of lower fidelity replication. When a unique beneficial mutation arises and sweeps to fixation, genetic hitchhiking may cause a substantial change in the frequency of a modifier of mutation rate. In previous studies of the evolution of mutation rates in sexual populations, this effect has been underestimated. This article models the long-term effect of a series of such hitchhiking events and determines the resulting strength of indirect selection on the modifier. This is compared to the indirect selection due to deleterious mutations, when both types of mutations are randomly scattered over a given genetic map. Relative to an asexual population, increased levels of recombination reduce the effects of beneficial mutations more rapidly than those of deleterious mutations. However, the role of beneficial mutations in determining the evolutionarily stable mutation rate may still be significant if the function describing the cost of high-fidelity replication has a shallow gradient.

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Modifiers of mutation-selection balance: general approach and the evolution of mutation rates

Genetics Research ◽

10.1017/s001667230003439x ◽

1995 ◽

Vol 66 (1) ◽

pp. 53-69 ◽

Cited By ~ 71

Author(s):

Alexey S. Kondrashov

Keyword(s):

Mutation Rate ◽

Mutant Allele ◽

Deleterious Mutation ◽

Mutation Rates ◽

Quasi Equilibrium ◽

Selection Differential ◽

Selection Coefficient ◽

Modifier Locus ◽

Ratio Of Variances ◽

The Cost

SummaryA general approach is developed to estimate secondary selection at a modifier locus that influences some feature of a population under mutation-selection balance. The approach is based on the assumption that the properties of all available genotypes at this locus are similar. Then mutation-selection balance and weak associations between genotype distributions at selectable loci and the modifier locus are established rapidly. In contrast, changes of frequencies of the modifier genotypes are slow, and lead to only slow and small changes of the other features of the population. Thus, while these changes occur, the population remains in a state of quasi-equilibrium, where the mutation-selection balance and the associations between the selectable loci and the modifier locus are almost invariant. Selection at the modifier locus can be estimated by calculating quasiequilibrium values of these associations. This approach is developed for the situation where distributions of the number of mutations per genome within the individuals with a given modifier genotype are close to Gaussian. The results are used to study the evolution of the mutation rate. Because beneficial mutations are ignored, secondary selection at the modifier locus always diminishes the mutation rate. The coefficient of selection against an allele which increases the mutation rate by υ is approximately υδ2/[U(2−ρ)] = υŝ, where υ is the genomic deleterious mutation rate, δ is the selection differential of the number of mutations per individual in units of the standard deviation of the distribution of this number in the population, ρ is the ratio of variances of the number of mutations after and before selection, and ŝ is the selection coefficient against a mutant allele in the quasiequilibrium population. However, the decline of the mutation rate can be counterbalanced by the cost of fidelity, which can lead to an evolutionary equilibrium mutation rate.

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Molecular mechanisms involved in the regulation of mutation rates in bacteria

Periodicum Biologorum ◽

10.18054/pb.v118i4.4601 ◽

2017 ◽

Vol 118 (4) ◽

Cited By ~ 4

Author(s):

Ivan Matic

Keyword(s):

Mutation Rate ◽

Molecular Mechanisms ◽

Point Of View ◽

Mutation Rates ◽

Beneficial Mutations ◽

Bacterial Populations ◽

Multiple Strategies ◽

Induced Mutagenesis ◽

The Cost ◽

Evolutionary Point

Organisms live in constantly changing environments in which, the nature, severity and frequency of the environmental stresses are very variable. Organisms possess multiple strategies for coping with the environmental fluctuations. One such strategy is modulation of mutation rates as a function of the degree of adaptation to the environment. When adaptation is limited by the available genetic variability, natural selection favors cells having high mutation rates in bacterial populations. High mutation rates can be advantageous because they increase the probability of generation of beneficial mutations. Constitutive mutator alleles are carried to high frequency through hitchhiking with beneficial mutations they generate. However, once the adaptation is achieved, the cost of deleterious mutations generated by constitutive mutator alleles reduces cellular fitness. For this reason, the possibility of adapting the mutation rate to environmental conditions is interesting from an evolutionary point of view. Stress-induced mutagenesis allows rapid adaptation to complex environmental challenges without compromising the population fitness because it reduces the overall cost of a high mutation rate. Here we review the molecular mechanisms involved in the control of modulation of mutation rates in bacteria.

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