scholarly journals Rapid evolution of the human mutation spectrum

2016 ◽  
Author(s):  
Kelley Harris ◽  
Jonathan K. Pritchard
Keyword(s):  
Mutation Rate ◽  
Genetic Modifier ◽  
Rapid Evolution ◽  
Biological Information ◽  
Mutation Rates ◽  
Specific Sequence ◽  
Mutational Spectra ◽  
Damage Repair ◽  
Human Mutation ◽  
System Selection

AbstractDNA is a remarkably precise medium for copying and storing biological information. This high fidelity results from the action of hundreds of genes involved in replication, proofreading, and damage repair. Evolutionary theory suggests that in such a system, selection has limited ability to remove genetic variants that change mutation rates by small amounts or in specific sequence contexts. Consistent with this, using SNV variation as a proxy for mutational input, we report here that mutational spectra differ substantially among species, human continental groups and even some closely-related populations. Close examination of one signal, an increased TCC→TTC mutation rate in Europeans, indicates a burst of mutations from about 15,000 to 2,000 years ago, perhaps due to the appearance, drift, and ultimate elimination of a genetic modifier of mutation rate. Our results suggest that mutation rates can evolve markedly over short evolutionary timescales and suggest the possibility of mapping mutational modifiers.

scholarly journals Rapid evolution of the human mutation spectrum

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Kelley Harris ◽  
Jonathan K Pritchard
Keyword(s):  
Mutation Rate ◽  
Genetic Modifier ◽  
Rapid Evolution ◽  
Biological Information ◽  
Mutation Rates ◽  
Specific Sequence ◽  
Mutational Spectra ◽  
Damage Repair ◽  
Human Mutation ◽  
System Selection

DNA is a remarkably precise medium for copying and storing biological information. This high fidelity results from the action of hundreds of genes involved in replication, proofreading, and damage repair. Evolutionary theory suggests that in such a system, selection has limited ability to remove genetic variants that change mutation rates by small amounts or in specific sequence contexts. Consistent with this, using SNV variation as a proxy for mutational input, we report here that mutational spectra differ substantially among species, human continental groups and even some closely related populations. Close examination of one signal, an increased TCC→TTC mutation rate in Europeans, indicates a burst of mutations from about 15,000 to 2000 years ago, perhaps due to the appearance, drift, and ultimate elimination of a genetic modifier of mutation rate. Our results suggest that mutation rates can evolve markedly over short evolutionary timescales and suggest the possibility of mapping mutational modifiers.

Potential DNA methods for measuring the human heritable mutation rate

Genome ◽  
1989 ◽  
Vol 31 (2) ◽  
pp. 860-863 ◽  
Author(s):  
Mortimer L. Mendelsohn
Keyword(s):  
Mutation Rate ◽  
Human Sperm ◽  
Mutation Rates ◽  
Practical Implementation ◽  
Dna Technology ◽  
Heritable Mutation ◽  
Human Mutation ◽  
Potential Methods

Potential methods are reviewed for estimating human heritable mutation rates by comparing the DNA of parents and offspring. In the 4 years since the Alta Workshop on this subject, information has accumulated on several of the six methods detailed in that meeting. Some of the methods now appear to be infeasible, and all continue to be too inefficient for practical implementation. Newer DNA approaches are discussed, including several that could become practical enough for implementation. Finally, DNA-oriented methods using human sperm are considered as possible alternatives to the heritable approaches.Key words: human heritable mutation, human mutation rate, DNA method – DNA technology, radiation.

scholarly journals DNA local structure decreases mutation rates

2018 ◽  
Author(s):  
Chaorui Duan ◽  
Qing Huan ◽  
Xiaoshu Chen ◽  
Shaohuan Wu ◽  
Lucas B. Carey ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Local Structure ◽  
Yeast Cells ◽  
Mutation Rates ◽  
Driver Mutations ◽  
Dna Curvature ◽  
Sequence Motifs ◽  
Specific Sequence ◽  
Synthetic Genes ◽  
Mutagen Sensitivity

ABSTRACTBackgroundMutation rates vary across the genome. Whereas manytransfactors that influence mutation rates have been identified, as have specific sequence motifs at the 1-7 bp scale,ciselements remain poorly characterized. The lack of understanding why different sequences have different mutation rates hampers our ability to identify positive selection in evolution and to identify driver mutations in tumorigenesis.ResultsHere we show, using a combination of synthetic genes and sequencing of thousands of isolated yeast colonies, that intrinsic DNA curvature is the majorcisdeterminant of mutation rate. Mutation rate negatively correlates with DNA curvature within genes, and a 10% decrease in curvature results in a 70% increase in mutation rate. Consistently, both yeast cells and human tumors accumulate mutations in regions with small curvature. We further show that this effect is due to differences in the intrinsic mutation rate, likely due to differences in mutagen sensitivity, and not due to differences in the local activity of DNA repair.ConclusionsOur study establishes a framework in understanding thecisproperties of DNA sequence in modulating the local mutation rate and identifies a novel causal source of non-uniform mutation rates across the genome.

scholarly journals The mutation rates and mutational bias of influenza A virus

2017 ◽  
Author(s):  
Matthew D. Pauly ◽  
Megan Procario ◽  
Adam S. Lauring
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Mutation Rate ◽  
Influenza A ◽  
Rapid Evolution ◽  
Viral Fitness ◽  
High Mutation Rate ◽  
Mutation Rates ◽  
Mutational Bias ◽  
Neutral Mutations

AbstractInfluenza virus has a high mutation rate, and this low replicative fidelity contributes to its capacity for rapid evolution. Clonal sequencing and fluctuation tests have suggested that the mutation rate of influenza A virus is 7.1 × 10−6− 4.5 × 10−5substitutions per nucleotide per cell infection cycle and 2.7 × 10−6− 3.0 × 10−5substitutions per nucleotide per strand copied (s/n/r). However, sequencing assays are biased toward mutations with minimal impacts on viral fitness and fluctuation tests typically investigate only a subset of the twelve mutational classes. We developed a fluctuation test based on reversion to fluorescence in a set of virally encoded mutant green fluorescent proteins. This method allowed us to measure the rates of selectively neutral mutations representative of all 12 mutational classes in the context of an unstructured RNA. We measured an overall mutation rate of 1.8 × 10−4s/n/r for PR8 (H1N1) and 2.5 × 10−4s/n/r for Hong Kong 2014 (H3N2). The replication mode was linear. The mutation rates of these divergent strains are significantly higher than previous estimates and suggest that each replicated genome will have an average of 2-3 mutations. The viral mutational spectrum is heavily biased toward A to G and U to C transitions, resulting in a transition to transversion bias of 2.7 and 3.6 for the two strains. These mutation rates were relatively constant over a range of physiological temperatures. Our high-resolution analysis of influenza virus mutation rates will enable more refined models of its molecular evolution.SignificanceThe rapid evolution of influenza virus is a major problem in public health. A key factor driving this rapid evolution is the virus’ very high mutation rate. We developed a new method for measuring the rates of all 12 mutational classes in influenza virus, which eliminates some of the biases of existing assays. We find that the influenza virus mutation rate is much higher than previously reported and is consistent across two distinct strains and a range of temperatures. Our data suggest that influenza viruses replicate at their maximally tolerable mutation rates, highlighting both the virus’ evolutionary potential and its significant constraints.

scholarly journals Direct estimation of mutations in great apes reveals significant recent human slowdown in the yearly mutation rate

2018 ◽  
Author(s):  
Søren Besenbacher ◽  
Christina Hvilsom ◽  
Tomas Marques-Bonet ◽  
Thomas Mailund ◽  
Mikkel Heide Schierup
Keyword(s):  
Linear Relationship ◽  
Mutation Rate ◽  
Fossil Record ◽  
Great Apes ◽  
Mutation Rates ◽  
Rate Estimate ◽  
The Past ◽  
Divergence Estimates ◽  
Human Mutation ◽  
Mutation Rate Estimate

AbstractThe human mutation rate per generation estimated from trio sequencing has revealed an almost linear relationship with the age of the father and the age of the mother. The yearly trio-based mutation rate estimate of ~0.43×10−9 is markedly lower than prior indirect estimates of ~1×10−9 per year from phylogenetic comparisons of the great apes. This suggests either a slowdown over the past 10 million years or an inaccurate interpretation of the fossil record. Here we use sequencing of chimpanzee, gorilla and orangutan trios and find that each species has higher estimated mutation rates per year by factors of 1.67+/− 0.22, 1.54+/− 0.2 and 1.84+/− 0.19, respectively. These estimates suggest a very recent and appreciable slowdown in human mutation rate, and, if extrapolated over the great apes phylogeny, yields divergence estimates much more in line with the fossil record and the biogeography.

scholarly journals Calibrating the Human Mutation Rate via Ancestral Recombination Density in Diploid Genomes

PLoS Genetics ◽  
2015 ◽  
Vol 11 (11) ◽  
pp. e1005550 ◽  
Author(s):  
Mark Lipson ◽  
Po-Ru Loh ◽  
Sriram Sankararaman ◽  
Nick Patterson ◽  
Bonnie Berger ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Human Mutation

scholarly journals Mutation rate analysis via parent–progeny sequencing of the perennial peach. II. No evidence for recombination-associated mutation

2016 ◽  
Vol 283 (1841) ◽  
pp. 20161785 ◽  
Author(s):  
Long Wang ◽  
Yanchun Zhang ◽  
Chao Qin ◽  
Dacheng Tian ◽  
Sihai Yang ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Recombination Rate ◽  
Mutation Rates ◽  
Recombination Rates ◽  
Rate Analysis ◽  
A Genome ◽  
Break Points ◽  
New Mutations

Mutation rates and recombination rates vary between species and between regions within a genome. What are the determinants of these forms of variation? Prior evidence has suggested that the recombination might be mutagenic with an excess of new mutations in the vicinity of recombination break points. As it is conjectured that domesticated taxa have higher recombination rates than wild ones, we expect domesticated taxa to have raised mutation rates. Here, we use parent–offspring sequencing in domesticated and wild peach to ask (i) whether recombination is mutagenic, and (ii) whether domesticated peach has a higher recombination rate than wild peach. We find no evidence that domesticated peach has an increased recombination rate, nor an increased mutation rate near recombination events. If recombination is mutagenic in this taxa, the effect is too weak to be detected by our analysis. While an absence of recombination-associated mutation might explain an absence of a recombination–heterozygozity correlation in peach, we caution against such an interpretation.

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