Meiosis and the Evolution of Recombination at Low Mutation Rates

Genetics ◽  
2000 ◽  
Vol 156 (1) ◽  
pp. 449-456 ◽  
Author(s):  
Damian D G Gessler ◽  
Shizhong Xu
Keyword(s):  
Dna Damage ◽  
Linkage Disequilibrium ◽  
Mutation Rate ◽  
Large Population ◽  
Mutation Rates ◽  
Selective Agent ◽  
Dna Mutation ◽  
Neutral Gene ◽  
Per Se ◽  
Asexual Populations

Abstract The classical understanding of recombination is that in large asexual populations with multiplicative fitness, linkage disequilibrium is negligible, and thus there is no selective agent driving an allele for recombination. This has led researchers to recognize the importance of synergistic epistatic selection in generating negative linkage disequilibrium that thereby renders an advantage to recombination. Yet data on such selection is equivocal, and various works have shown that synergistic epistasis per se, when left unquantified in its magnitude or operation, is not sufficient to drive the evolution of recombination. Here we show that neither it, nor any mechanism generating negative linkage disequilibrium among fitness-related loci, is necessary. We demonstrate that a neutral gene for recombination can increase in frequency in a large population under a low mutation rate and strict multiplicative fitness. We work in a parameter range where individuals have, on average, less than one mutation each, yet recombination can still evolve. We demonstrate this in two ways: first, by examining the consequences of recombination correlated with misrepaired DNA damage and, second, by increasing the probability of recombination with declining fitness. Interestingly, the allele spreads without repairing even a single DNA mutation.

scholarly journals Distinct evolutionary trajectories in asexual populations through an interplay of their size, resource availability and mutation rates

2020 ◽  
Author(s):  
Bhaskar Kumawat ◽  
Ramray Bhat
Keyword(s):  
Mutation Rate ◽  
Single Cells ◽  
Maximum Size ◽  
Mutation Rates ◽  
Genome Replication ◽  
Sequence Motifs ◽  
Complex Picture ◽  
Distinct Sequence ◽  
Resource Levels ◽  
Asexual Populations

AbstractAsexually reproducing populations of single cells evolve through mutation, natural selection, and genetic drift to enhance their reproductive fitness. The environment provides the contexts that allow and regulate their fitness dynamics. In this work, we used Avida - a digital evolution framework - to uncover the effect of mutation rates, maximum size of the population, and the relative abundance of resources, on evolutionary outcomes in asexually reproducing populations of digital organisms. We observed that over extended simulations, the population evolved predominantly to one of several discrete fitness classes, each with distinct sequence motifs and/or phenotypes. For a low mutation rate, the organisms acquired either of four fitness values through an enhancement in the rate of genomic replication. Evolution at a relatively higher mutation rate presented a more complex picture. While the highest fitness values at a high mutation rate were achieved through enhanced genome replication rates, a suboptimal one was achieved through organisms sharing information relevant to metabolic tasks with each other. The information sharing capacity was vital to fitness acquisition and frequency of the genotype associated with it increased with greater resource levels and maximum population size. In addition, populations optimizing their fitness through such means exhibited a greater degree of genotypic heterogeneity and metabolic activity than those that improved replication rates. Our results reveal a minimal set of conditions for the emergence of interdependence within evolving populations with significant implications for biological systems in appropriate environmental contexts.

scholarly journals The effect of known mutator alleles in a cluster of clinicalSaccharomyces cerevisiaestrains

2016 ◽  
Author(s):  
Daniel A. Skelly ◽  
Paul M. Magwene ◽  
Brianna Meeks ◽  
Helen A. Murphy
Keyword(s):  
Mutation Rate ◽  
Evolutionary Theory ◽  
Phylogenetic Analyses ◽  
Mutation Rates ◽  
Genetic Modifiers ◽  
Beneficial Mutations ◽  
Mutator Allele ◽  
Genomic Mutation ◽  
Asexual Populations ◽  
The Relationship

AbstractNatural selection has the potential to act on all phenotypes, including genomic mutation rate. Classic evolutionary theory predicts that in asexual populations, mutator alleles, which cause high mutation rates, can fix due to linkage with beneficial mutations. This phenomenon has been demonstrated experimentally and may explain the frequency of mutators found in bacterial pathogens. In contrast, in sexual populations, recombination decouples mutator alleles from beneficial mutations, preventing mutator fixation. In the facultatively sexual yeastSaccharomyces cerevisiae, segregating alleles ofMLH1andPMS1have been shown to be incompatible, causing a high mutation rate when combined. These alleles had never been found together naturally, but were recently discovered in a cluster of clinical isolates. Here we report that the incompatible mutator allele combination only marginally elevates mutation rate in these clinical strains. Genomic and phylogenetic analyses provide no evidence of a historically elevated mutation rate. We conclude that the effect of the mutator alleles is dampened by background genetic modifiers. Thus, the relationship between mutation rate and microbial pathogenicity may be more complex than once thought. Our findings provide rare observational evidence that supports evolutionary theory suggesting that sexual organisms are unlikely to harbor alleles that increase their genomic mutation rate.

scholarly journals Expression of progerin does not result in an increased mutation rate

2016 ◽  
Author(s):  
Emmanuelle Deniaud ◽  
Shelagh Boyle ◽  
Wendy Bickmore
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dna Damage Response ◽  
Mutation Rate ◽  
Genetic Defect ◽  
Lamin A ◽  
Mutant Form ◽  
Premature Ageing ◽  
Damage Response ◽  
Per Se

AbstractIn the premature ageing disease Hutchinson-Gilford progeria syndrome (HGPS) the underlying genetic defect in the lamin A gene leads to accumulation at the nuclear lamina of progerin – a mutant form of lamin A that cannot be correctly processed. This has been reported to result in defects in the DNA damage response and in DNA repair, leading to the hypothesis that, as in normal ageing and in other progeroid syndromes caused by mutation of genes of the DNA repair and DNA damage response pathways, increased DNA damage may be responsible for the premature ageing phenotypes in HGPS patients. However, this hypothesis is based upon the study of markers of the DNA damage response, rather than measurement of DNA damage per se or the consequences of unrepaired DNA damage -mutation. Here, using a mutation reporter cell line, we directly compared the inherent and induced mutation rates in cells expressing wild-type lamin A or progerin. We find no evidence for an elevated mutation rate in progerin-expressing cells. We conclude that the cellular defect in HGPS cells does not lie in the repair of DNA damage per se.

scholarly journals Mutation rate estimation for 15 autosomal STR loci in a large population from Mainland China

2015 ◽  
Author(s):  
Zhuo Zhao ◽  
Hua Wang ◽  
Jie Zhang ◽  
Zhi-Peng Liu ◽  
Ming Liu ◽  
...  
Keyword(s):  
Population Genetics ◽  
Mutation Rate ◽  
Large Population ◽  
Mainland China ◽  
Mutation Rates ◽  
Str Analysis ◽  
Str Loci ◽  
Autosomal Str ◽  
Parents And Children ◽  
Genetic Assessment

STR, short trandem repeats, is well known as a type of powerful genetic marker and widely used in studying human population genetics. Compared with the conventional genetic markers, the mutation rate of STR is higher. Additionally, the mutations of STR loci do not lead to genetic inconsistencies between the genotypes of parents and children; therefore, the analysis of STR mutation is more suited to assess the population mutation. In this study, we focused on 15 autosomal STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, FGA). DNA samples from a total of 42416 unrelated healthy individuals (19037 trios) from the population of Mainland China collected between Jan 2012 and May 2014 were successfully investigated. In our study, the allele frequencies, paternal mutation rates, maternal mutation rates and average mutation rates were detected in the 15 STR loci. Furthermore, we also investigated the relationship between paternal ages, maternal ages, pregnant time, area and average mutation rate. We found that paternal mutation rate is higher than maternal mutation rate and the paternal, maternal, and average mutation rates have a positive correlation with paternal ages, maternal ages and times respectively. Additionally, the average mutation rates of coastal areas are higher than that of inland areas. Overall, these results suggest that the 15 autosomal STR loci can provide highly informative polymorphic data for population genetic assessment in Mainland China, as well as confirm and extend the application of STR analysis in population genetics.

scholarly journals Evolution of Mutation Rate in Astronomically Large Phytoplankton Populations

2020 ◽  
Vol 12 (7) ◽  
pp. 1051-1059
Author(s):  
Marc Krasovec ◽  
Rosalind E M Rickaby ◽  
Dmitry A Filatov
Keyword(s):  
Genetic Diversity ◽  
Population Size ◽  
Mutation Rate ◽  
Spontaneous Mutation ◽  
Large Population ◽  
Marine Phytoplankton ◽  
Mutation Rates ◽  
Effective Population ◽  
Spontaneous Mutation Rate ◽  
Large Populations

Abstract Genetic diversity is expected to be proportional to population size, yet, there is a well-known, but unexplained lack of genetic diversity in large populations—the “Lewontin’s paradox.” Larger populations are expected to evolve lower mutation rates, which may help to explain this paradox. Here, we test this conjecture by measuring the spontaneous mutation rate in a ubiquitous unicellular marine phytoplankton species Emiliania huxleyi (Haptophyta) that has modest genetic diversity despite an astronomically large population size. Genome sequencing of E. huxleyi mutation accumulation lines revealed 455 mutations, with an unusual GC-biased mutation spectrum. This yielded an estimate of the per site mutation rate µ = 5.55×10−10 (CI 95%: 5.05×10−10 – 6.09×10−10), which corresponds to an effective population size Ne ∼ 2.7×106. Such a modest Ne is surprising for a ubiquitous and abundant species that accounts for up to 10% of global primary productivity in the oceans. Our results indicate that even exceptionally large populations do not evolve mutation rates lower than ∼10−10 per nucleotide per cell division. Consequently, the extreme disparity between modest genetic diversity and astronomically large population size in the plankton species cannot be explained by an unusually low mutation rate.

Mutation rates in the dihydrofolate reductase gene of Plasmodium falciparum

Parasitology ◽  
2001 ◽  
Vol 122 (5) ◽  
pp. 497-505 ◽  
Author(s):  
S. PAGET-MCNICOL ◽  
A. SAUL
Keyword(s):  
Plasmodium Falciparum ◽  
Mathematical Modelling ◽  
Mutation Rate ◽  
Dihydrofolate Reductase ◽  
Large Scale ◽  
Spontaneous Mutation ◽  
Large Population ◽  
Mutation Rates ◽  
Dhfr Gene ◽  
Drug Pressure

A new method has been established to define the limits on a spontaneous mutation rate for a gene in Plasmodium falciparum. The method combines mathematical modelling and large-scale in vitro culturing and calculates the difference in mutant frequencies at 2 separate time-points. We measured the mutation rate at 2 positions in the dihydrofolate reductase (DHFR) gene of 3D7, a pyrimethamine-sensitive line of P. falciparum. This line was re-cloned and an effectively large population was treated with a selective pyrimethamine concentration of 40 nM. We detected point mutations at codon-46 (TTA to TCA) and codon-108 (AGC to AAC), resulting in serine replacing leucine and asparagine replacing serine respectively in the corresponding gene product. The substitutions caused a decrease in pyrimethamine sensitivity. By mathematical modelling we determined that the mutation rate at a given position in DHFR was low and occurred at less than 2.5×10−9 mutations/DHFR gene/replication. This result has important implications for Plasmodium genetic diversity and anti-malarial drug therapy by demonstrating that even with low mutation rates anti-malarial resistance will inevitably arise when mutant alleles are selected under drug pressure.

scholarly journals Linkage disequilibrium and genetic variances under mutation-selection balance.

Genetics ◽  
1989 ◽  
Vol 121 (4) ◽  
pp. 857-860 ◽  
Author(s):  
A Hastings
Keyword(s):  
Linkage Disequilibrium ◽  
Mutation Rate ◽  
Genetic Variance ◽  
Harmonic Mean ◽  
Recombination Rates ◽  
Genetic Variances ◽  
Locus Selection

Abstract I determine the contribution of linkage disequilibrium to genetic variances using results for two loci and for induced or marginal systems. The analysis allows epistasis and dominance, but assumes that mutation is weak relative to selection. The linkage disequilibrium component of genetic variance is shown to be unimportant for unlinked loci if the gametic mutation rate divided by the harmonic mean of the pairwise recombination rates is much less than one. For tightly linked loci, linkage disequilibrium is unimportant if the gametic mutation rate divided by the (induced) per locus selection is much less than one.

scholarly journals SETD2 alterations impair DNA damage recognition and lead to resistance to chemotherapy in leukemia

Blood ◽  
2017 ◽  
Vol 130 (24) ◽  
pp. 2631-2641 ◽  
Author(s):  
Brenton G. Mar ◽  
S. Haihua Chu ◽  
Josephine D. Kahn ◽  
Andrei V. Krivtsov ◽  
Richard Koche ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Mutation Rate ◽  
Histone 3 ◽  
Damage Recognition ◽  
Key Points ◽  
Damage Response ◽  
Dna Damage Recognition ◽  
Resistance To Chemotherapy

Key Points Alterations of SETD2, a histone 3 lysine 36 trimethyl (H3K36me3) transferase leads to resistance to DNA damaging-chemotherapy in leukemia. Low H3K36me3 levels impair DNA damage response and increase mutation rate, which may be targeted by H3K36me3 demethylase inhibition.

scholarly journals Ecological Divergence and the Origins of Intrinsic Postmating Isolation with Gene Flow

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Aneil F. Agrawal ◽  
Jeffrey L. Feder ◽  
Patrik Nosil
Keyword(s):  
Linkage Disequilibrium ◽  
Gene Flow ◽  
Natural Selection ◽  
Theoretical Models ◽  
Ecological Speciation ◽  
Divergent Selection ◽  
Postmating Isolation ◽  
Divergent Natural Selection ◽  
Mathematical Exploration ◽  
Neutral Gene

The evolution of intrinsic postmating isolation has received much attention, both historically and in recent studies of speciation genes. Intrinsic isolation often stems from between-locus genetic incompatibilities, where alleles that function well within species are incompatible with one another when brought together in the genome of a hybrid. It can be difficult for such incompatibilities to originate when populations diverge with gene flow, because deleterious genotypic combinations will be created and then purged by selection. However, it has been argued that if genes underlying incompatibilities are themselves subject to divergent selection, then they might overcome gene flow to diverge between populations, resulting in the origin of incompatibilities. Nonetheless, there has been little explicit mathematical exploration of such scenarios for the origin of intrinsic incompatibilities during ecological speciation with gene flow. Here we explore theoretical models for the origin of intrinsic isolation where genes subject to divergent natural selection also affect intrinsic isolation, either directly or via linkage disequilibrium with other loci. Such genes indeed overcome gene flow, diverge between populations, and thus result in the evolution of intrinsic isolation. We also examine barriers to neutral gene flow. Surprisingly, we find that intrinsic isolation sometimes weakens this barrier, by impeding differentiation via ecologically based divergent selection.

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