scholarly journals Mutation-Selection Balance, Dominance and the Maintenance of Sex

Genetics ◽  
2000 ◽  
Vol 156 (3) ◽  
pp. 1419-1425
Author(s):  
J R Chasnov
Keyword(s):  
Mutation Rate ◽  
Gene Locus ◽  
Necessary Conditions ◽  
Deleterious Mutations ◽  
Sexual Population ◽  
Recessive Mutations ◽  
Maintenance Of Sex ◽  
A Genome ◽  
Evolutionary Function ◽  
Mean Fitness

Abstract A leading hypothesis for the evolutionary function of sex postulates that sex is an adaptation that purges deleterious mutations from the genome, thereby increasing the equilibrium mean fitness of a sexual population relative to its asexual competitor. This hypothesis requires two necessary conditions: first, the mutation rate per genome must be of order one, and, second, multiple mutations within a genome must act with positive epistasis, that is, two or more mutations of different genes must be more harmful together than if they acted independently. Here, by reconsidering the theory of mutation-selection balance at a single diploid gene locus, we demonstrate a significant advantage of sex due to nearly recessive mutations provided the mutation rate per genome is of order one. The assumption of positive epistasis is unnecessary, and multiple mutations may be assumed to act independently.

scholarly journals Expansion load: recessive mutations and the role of standing genetic variation

2014 ◽  
Author(s):  
Stephan Peischl ◽  
Laurent Excoffier
Keyword(s):  
Genetic Variation ◽  
Species Range ◽  
Human Populations ◽  
Deleterious Mutations ◽  
Recessive Mutations ◽  
Mutation Burden ◽  
Natural Range ◽  
Mean Fitness ◽  
Expansion Load

Expanding populations incur a mutation burden – the so-called expansion load. Previous studies of expansion load have focused on co-dominant mutations. An important consequence of this assumption is that expansion load stems exclusively from the accumulation of new mutations occurring in individuals living at the wave front. Using individual-based simulations we study here the dynamics of standing genetic variation at the front of expansions, and its consequences on mean fitness if mutations are recessive. We find that deleterious genetic diversity is quickly lost at the front of the expansion, but the loss of deleterious mutations at some loci is compensated by an increase of their frequencies at other loci. The frequency of deleterious homozygotes therefore increases along the expansion axis whereas the average number of deleterious mutations per individual remains nearly constant across the species range. This reveals two important differences to co-dominant models: (i) mean fitness at the front of the expansion drops much faster if mutations are recessive, and (ii) mutation load can increase during the expansion even if the total number of deleterious mutations per individual remains constant. We use our model to make predictions about the shape of the site frequency spectrum at the front of range expansion, and about correlations between heterozygosity and fitness in different parts of the species range. Importantly, these predictions provide opportunities to empirically validate our theoretical results. We discuss our findings in the light of recent results on the distribution of deleterious genetic variation across human populations, and link them to empirical results on the correlation of heterozygosity and fitness found in many natural range expansions.

scholarly journals Mutation-selection balance and the evolutionary advantage of sex and recombination

1990 ◽  
Vol 55 (3) ◽  
pp. 199-221 ◽  
Author(s):  
Brian Charlesworth
Keyword(s):  
Mutation Rate ◽  
Genetic Recombination ◽  
Random Mating ◽  
Quantitative Character ◽  
Sexual Population ◽  
Evolutionary Advantage ◽  
Diminishing Returns ◽  
Mean Fitness ◽  
Locus System ◽  
Asexual Populations

SummaryMutation-selection balance in a multi-locus system is investigated theoretically, using a modification of Bulmer's infinitesimal model of selection on a normally-distributed quantitative character, taking the number of mutations per individual (n) to represent the character value. The logarithm of the fitness of an individual with n mutations is assumed to be a quadratic, decreasing function of n. The equilibrium properties of infinitely large asexual populations, random-mating populations lacking genetic recombination, and random-mating populations with arbitrary recombination frequencies are investigated. With ‘synergistic’ epistasis on the scale of log fitness, such that log fitness declines more steeply as n increases, it is shown that equilibrium mean fitness is least for asexual populations. In sexual populations, mean fitness increases with the number of chromosomes and with the map length per chromosome. With ‘diminishing returns’ epistasis, such that log fitness declines less steeply as n increases, mean fitness behaves in the opposite way. Selection on asexual variants and genes affecting the rate of genetic recombination in random-mating populations was also studied. With synergistic epistasis, zero recombination always appears to be disfavoured, but free recombination is disfavoured when the mutation rate per genome is sufficiently small, leading to evolutionary stability of maps of intermediate length. With synergistic epistasis, an asexual mutant is unlikely to invade a sexual population if the mutation rate per diploid genome greatly exceeds unity. Recombination is selectively disadvantageous when there is diminishing returns epistasis. These results are compared with the results of previous theoretical studies of this problem, and with experimental data.

scholarly journals Population heterogeneity in mutation rate increases mean fitness and the frequency of higher order mutants

2016 ◽  
Author(s):  
Helen K. Alexander ◽  
Stephanie I. Mayer ◽  
Sebastian Bonhoeffer
Keyword(s):  
Mutation Rate ◽  
Relative Effect ◽  
Relative Increase ◽  
Higher Order ◽  
Population Heterogeneity ◽  
Arbitrary Distribution ◽  
Rate Heterogeneity ◽  
Standing Variation ◽  
A Genome ◽  
Mean Fitness

AbstractMutation rate is a crucial evolutionary parameter that has typically been treated as a constant in population genetic analyses. However, mutation rate is likely to vary among co-existing individuals within a population, due to genetic polymorphisms, heterogeneous environmental influences, and random physiological fluctuations. We explore the consequences of such mutation rate heterogeneity in a model allowing an arbitrary distribution of mutation rate among individuals, either with or without inheritance. We find that variation of mutation rate about the mean results in a higher probability of producing zero or many simultaneous mutations on a genome. Moreover, it increases the frequency of higher order mutants even under ongoing mutation and selection. We gain a quantitative understanding of how this frequency depends on moments of the mutation rate distribution and selection coefficients. In particular, in a two-locus model, heterogeneity leads to a relative increase in double mutant frequency proportional to the squared coefficient of variation of the mutation rate. Relative effect sizes increase with the number of loci. Finally, this clustering of deleterious mutations into fewer individuals results in a higher population mean fitness. Our results imply that mutation rate heterogeneity allows a population to maintain a higher level of adaptedness to its current environment, while simultaneously harboring greater genetic diversity in the standing variation, which could be crucial for future adaptation to a new environment. Our results also have implications for interpreting mutation rate estimates and mutant frequencies in data.

Recessive Mutations and the Maintenance of Sex in Structured Populations

Genetics ◽  
2001 ◽  
Vol 158 (2) ◽  
pp. 913-917 ◽  
Author(s):  
Aneil F Agrawal ◽  
J R Chasnov
Keyword(s):  
Population Structure ◽  
Structured Populations ◽  
Deleterious Mutations ◽  
Recessive Mutations ◽  
Maintenance Of Sex ◽  
Controversial Problem ◽  
Low Levels ◽  
Asexual Populations ◽  
The Cost ◽  
Cost Of Sex

AbstractThe evolutionary maintenance of sexual reproduction remains a controversial problem. It was recently shown that recessive deleterious mutations create differences in the mutation load of sexual vs. asexual populations. Here we show that low levels of population structure or inbreeding can greatly enhance the importance of recessive deleterious mutations in the context of sexual vs. asexual populations. With population structure, the cost of sex can be substantially reduced or even eliminated for realistic levels of dominance.

scholarly journals Rate and effects of spontaneous mutations that affect fitness in mutator Escherichia coli

2010 ◽  
Vol 365 (1544) ◽  
pp. 1177-1186 ◽  
Author(s):  
Sandra Trindade ◽  
Lilia Perfeito ◽  
Isabel Gordo
Keyword(s):  
Escherichia Coli ◽  
Mutation Rate ◽  
Deleterious Mutation ◽  
Natural Populations ◽  
Estimation Methods ◽  
Single Individual ◽  
Deleterious Mutations ◽  
Spontaneous Mutations ◽  
Mutator Strain ◽  
Mean Fitness

Knowledge of the mutational parameters that affect the evolution of organisms is of key importance in understanding the evolution of several characteristics of many natural populations, including recombination and mutation rates. In this study, we estimated the rate and mean effect of spontaneous mutations that affect fitness in a mutator strain of Escherichia coli and review some of the estimation methods associated with mutation accumulation (MA) experiments. We performed an MA experiment where we followed the evolution of 50 independent mutator lines that were subjected to repeated bottlenecks of a single individual for approximately 1150 generations. From the decline in mean fitness and the increase in variance between lines, we estimated a minimum mutation rate to deleterious mutations of 0.005 (±0.001 with 95% confidence) and a maximum mean fitness effect per deleterious mutation of 0.03 (±0.01 with 95% confidence). We also show that any beneficial mutations that occur during the MA experiment have a small effect on the estimate of the rate and effect of deleterious mutations, unless their rate is extremely large. Extrapolating our results to the wild-type mutation rate, we find that our estimate of the mutational effects is slightly larger and the inferred deleterious mutation rate slightly lower than previous estimates obtained for non-mutator E. coli .

scholarly journals On the Rate and Linearity of Viability Declines in Drosophila Mutation-Accumulation Experiments: Genomic Mutation Rates and Synergistic Epistasis Revisited

Genetics ◽  
2004 ◽  
Vol 166 (2) ◽  
pp. 797-806 ◽  
Author(s):  
James D Fry
Keyword(s):  
Mutation Rate ◽  
Average Rate ◽  
Natural Populations ◽  
Mutation Accumulation ◽  
High Rate ◽  
Deleterious Mutations ◽  
Order Of Magnitude ◽  
Contamination Event ◽  
Genomic Mutation ◽  
The 1960S

Abstract High rates of deleterious mutations could severely reduce the fitness of populations, even endangering their persistence; these effects would be mitigated if mutations synergize each others’ effects. An experiment by Mukai in the 1960s gave evidence that in Drosophila melanogaster, viability-depressing mutations occur at the surprisingly high rate of around one per zygote and that the mutations interact synergistically. A later experiment by Ohnishi seemed to support the high mutation rate, but gave no evidence for synergistic epistasis. Both of these studies, however, were flawed by the lack of suitable controls for assessing viability declines of the mutation-accumulation (MA) lines. By comparing homozygous viability of the MA lines to simultaneously estimated heterozygous viability and using estimates of the dominance of mutations in the experiments, I estimate the viability declines relative to an appropriate control. This approach yields two unexpected conclusions. First, in Ohnishi’s experiment as well as in Mukai’s, MA lines showed faster-than-linear declines in viability, indicative of synergistic epistasis. Second, while Mukai’s estimate of the genomic mutation rate is supported, that from Ohnishi’s experiment is an order of magnitude lower. The different results of the experiments most likely resulted from differences in the starting genotypes; even within Mukai’s experiment, a subset of MA lines, which I argue probably resulted from a contamination event, showed much slower viability declines than did the majority of lines. Because different genotypes may show very different mutational behavior, only studies using many founding genotypes can determine the average rate and distribution of effects of mutations relevant to natural populations.

scholarly journals The mutation load under tetrasomic inheritance and its consequences for the evolution of the selfing rate in autotetraploid species

1999 ◽  
Vol 74 (1) ◽  
pp. 31-42 ◽  
Author(s):  
J. RONFORT
Keyword(s):  
Inbreeding Depression ◽  
Deleterious Mutation ◽  
Stable State ◽  
Approximate Solutions ◽  
Balance Model ◽  
Deleterious Mutations ◽  
Selfing Rate ◽  
Mutation Load ◽  
Mean Fitness ◽  
The Mean

Single-locus equilibrium frequencies of a partially recessive deleterious mutation under the mutation–selection balance model are derived for partially selfing autotetraploid populations. Assuming multiplicative fitness interactions among loci, approximate solutions for the mean fitness and inbreeding depression values are also derived for the multiple locus case and compared with expectations for the diploid model. As in diploids, purging of deleterious mutations through consanguineous matings occurs in autotetraploid populations, i.e. the equilibrium mutation load is a decreasing function of the selfing rate. However, the variation of inbreeding depression with the selfing rate depends strongly on the dominance coefficients associated with the three heterozygous genotypes. Inbreeding depression can either increase or decrease with the selfing rate, and does not always vary monotonically. Expected issues for the evolution of the selfing rate consequently differ depending on the dominance coefficients. In some cases, expectations for the evolution of the selfing rate resemble expectations in diploids; but particular sets of dominance coefficients can be found that lead to either complete selfing or intermediate selfing rates as unique evolutionary stable state.

Overproduction of yeast viruslike particles by strains deficient in a mitochondrial nuclease

1989 ◽  
Vol 9 (8) ◽  
pp. 3323-3331
Author(s):  
Y X Liu ◽  
C L Dieckmann
Keyword(s):  
Coat Protein ◽  
Killer Toxin ◽  
Nuclear Gene ◽  
Fold Increase ◽  
Mitochondrial Outer Membrane ◽  
Gene Encoding ◽  
Recessive Mutations ◽  
A Genome ◽  
Nonfermentable Carbon Source ◽  
Viruslike Particles

Saccharomyces cerevisiae strains are often host to several types of cytoplasmic double-stranded RNA (dsRNA) genomes, some of which are encapsidated by the L-A dsRNA product, an 86,000-dalton coat protein. Here we present the finding that nuclear recessive mutations in the NUC1 gene, which encodes the major nonspecific nuclease of yeast mitochondria, resulted in at least a 10-fold increase in amounts of the L-A dsRNA and its encoded coat protein. The effect of nuc1 mutations on L-A abundance was completely suppressed in strains that also hosted the killer-toxin-encoding M dsRNA. Both NUC1 and nuc1 strains containing the L-A genome exhibited an increase in coat protein abundance and a concomitant increase in L-A dsRNA when the cells were grown on a nonfermentable carbon source rather than on glucose, an effect independent of the increase in coat protein due to nuc1 mutations or to the absence of M. The increase in L-A expression in nuc1 strains was similar to that observed in strains with mutations in the nuclear gene encoding the most abundant outer mitochondrial membrane protein, porin. nuc1 mutations did not affect the level of porin in the mitochondrial outer membrane. Since the effect of mutations in nuc1 was to alter the copy number of the L-A coat protein genome rather than to change the level of the M toxin genome (as do mak and ski mutations), these mutations define a new class of nuclear genes affecting yeast dsRNA abundance.

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.

scholarly journals Genetic sex determination and sex-specific lifespan in tetrapods – evidence of a toxic Y effect

2020 ◽  
Author(s):  
Zahida Sultanova ◽  
Philip A. Downing ◽  
Pau Carazo
Keyword(s):  
Sex Chromosomes ◽  
Alternative Hypothesis ◽  
Z Chromosome ◽  
W Chromosome ◽  
Deleterious Mutations ◽  
Recessive Mutations ◽  
Y Chromosomes ◽  
Heterogametic Sex ◽  
Taxonomic Patterns

ABSTRACTSex-specific lifespans are ubiquitous across the tree of life and exhibit broad taxonomic patterns that remain a puzzle, such as males living longer than females in birds and vice versa in mammals. The prevailing “unguarded-X” hypothesis (UXh) explains this by differential expression of recessive mutations in the X/Z chromosome of the heterogametic sex (e.g., females in birds and males in mammals), but has only received indirect support to date. An alternative hypothesis is that the accumulation of deleterious mutations and repetitive elements on the Y/W chromosome might lower the survival of the heterogametic sex (“toxic Y” hypothesis). Here, we report lower survival of the heterogametic relative to the homogametic sex across 138 species of birds, mammals, reptiles and amphibians, as expected if sex chromosomes shape sex-specific lifespans. We then analysed bird and mammal karyotypes and found that the relative sizes of the X and Z chromosomes are not associated with sex-specific lifespans, contrary to UXh predictions. In contrast, we found that Y size correlates negatively with male survival in mammals, where toxic Y effects are expected to be particularly strong. This suggests that small Y chromosomes benefit male lifespans. Our results confirm the role of sex chromosomes in explaining sex differences in lifespan, but indicate that, at least in mammals, this is better explained by “toxic Y” rather than UXh effects.

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