scholarly journals Moderate amounts of epistasis are not evolutionarily stable in small populations

2019 ◽  
Author(s):  
Dariya K. Sydykova ◽  
Thomas LaBar ◽  
Christoph Adami ◽  
Claus O. Wilke
Keyword(s):  
Mutation Rates ◽  
Small Populations ◽  
Deleterious Mutations ◽  
Mutational Robustness ◽  
Agent Based ◽  
Lethal Mutagenesis ◽  
Unstable Fixed Point ◽  
Population Sizes ◽  
Evolutionary Trajectories ◽  
Evolutionarily Stable

AbstractHigh mutation rates select for the evolution of mutational robustness where populations inhabit flat fitness peaks with little epistasis, protecting them from lethal mutagenesis. Recent evidence suggests that a different effect protects small populations from extinction via the accumulation of deleterious mutations. In drift robustness, populations tend to occupy peaks with steep flanks and positive epistasis between mutations. However, it is not known what happens when mutation rates are high and population sizes are small at the same time. Using a simple fitness model with variable epistasis, we show that the equilibrium fitness has a minimum as a function of the parameter that tunes epistasis, implying that this critical point is an unstable fixed point for evolutionary trajectories. In agent-based simulations of evolution at finite mutation rate, we demonstrate that when mutations can change epistasis, trajectories with a subcritical value of epistasis evolve to decrease epistasis, while those with supercritical initial points evolve towards higher epistasis. These two fixed points can be identified with mutational and drift robustness, respectively.

scholarly journals Evolution of Drift Robustness in Small Populations

2016 ◽  
Author(s):  
Thomas LaBar ◽  
Christoph Adami
Keyword(s):  
Mathematical Modeling ◽  
Experimental Evolution ◽  
Small Population ◽  
Small Populations ◽  
Mutational Load ◽  
Deleterious Mutations ◽  
Mutational Robustness ◽  
Large Populations ◽  
Slightly Deleterious Mutations ◽  
Population Sizes

AbstractMost mutations are deleterious and cause a reduction in population fitness known as the mutational load. In small populations, weakened selection against slightly-deleterious mutations results in an additional fitness reduction. Many studies have established that populations can evolve a reduced mutational load by evolving mutational robustness, but it is uncertain whether small populations can evolve a reduced susceptibility to drift-related fitness declines. Here, using mathematical modeling and digital experimental evolution, we show that small populations do evolve a reduced vulnerability to drift, or “drift robustness”. We find that, compared to genotypes from large populations, genotypes from small populations have a decreased likelihood of small-effect deleterious mutations, thus causing small-population genotypes to be drift-robust. We further show that drift robustness is not adaptive, but instead arises because small populations preferentially adapt to drift-robust fitness peaks. These results have implications for genome evolution in organisms with small population sizes.

scholarly journals The Effects of Deleterious Mutations on Linked, Neutral Variation in Small Populations

Genetics ◽  
1999 ◽  
Vol 153 (1) ◽  
pp. 475-483 ◽  
Author(s):  
Snæbjörn Pálsson ◽  
Pekka Pamilo
Keyword(s):  
Small Populations ◽  
Background Selection ◽  
Deleterious Mutations ◽  
Selection Coefficient ◽  
Effective Population ◽  
Strong Reduction ◽  
Tight Linkage ◽  
Neutral Marker ◽  
Population Sizes ◽  
Clear Increase

Abstract The effects of recessive, deleterious mutations on genetic variation at linked neutral loci can be heterozygosity-decreasing because of reduced effective population sizes or heterozygosity-increasing because of associative overdominance. Here we examine the balance between these effects by simulating individual diploid genotypes in small panmictic populations. The haploid genome consists of one linkage group with 1000 loci that can have deleterious mutations and a neutral marker. Combinations of the following parameters are studied: gametic mutation rate to harmful alleles (U), population size (N), recombination rate (r), selection coefficient (s), and dominance (h). Tight linkage (r ≤ 10–4) gives significant associative effects, leading either to strong reduction of heterozygosity when the product Nhs is large or to a clear increase when the product Nhs is small, the boundary between these effects being 1 < Nhs < 4 in our simulations. Associative overdominance can lead to heterozygosities that are larger than predicted by the background selection models and even larger than the neutral expectation.

scholarly journals Germline Bottlenecks and the Evolutionary Maintenance of Mitochondrial Genomes

Genetics ◽  
1998 ◽  
Vol 149 (4) ◽  
pp. 2135-2146 ◽  
Author(s):  
Carl T Bergstrom ◽  
Jonathan Pritchard
Keyword(s):  
Equilibrium Distribution ◽  
Genetic Model ◽  
Mutation Rates ◽  
Mitochondrial Genomes ◽  
Uniparental Inheritance ◽  
Small Populations ◽  
Deleterious Mutations ◽  
Muller's Ratchet ◽  
Large Populations ◽  
Muller’S Ratchet

Abstract Several features of the biology of mitochondria suggest that mitochondria might be susceptible to Muller's ratchet and other forms of evolutionary degradation: Mitochondria have predominantly uniparental inheritance, appear to be nonrecombining, and have high mutation rates producing significant deleterious variation. We demonstrate that the persistence of mitochondria may be explained by recent data that point to a severe “bottleneck” in the number of mitochondria passing through the germline in humans and other mammals. We present a population-genetic model in which deleterious mutations arise within individual mitochondria, while selection operates on assemblages of mitochondria at the level of their eukaryotic hosts. We show that a bottleneck increases the efficacy of selection against deleterious mutations by increasing the variance in fitness among eukaryotic hosts. We investigate both the equilibrium distribution of deleterious variation in large populations and the dynamics of Muller's ratchet in small populations. We find that in the absence of the ratchet, a bottleneck leads to improved mitochondrial performance and that, over a longer time scale, a bottleneck acts to slow the progression of the ratchet.

scholarly journals Recombination Can Evolve in Large Finite Populations Given Selection on Sufficient Loci

Genetics ◽  
2003 ◽  
Vol 165 (4) ◽  
pp. 2249-2258 ◽  
Author(s):  
Mark M Iles ◽  
Kevin Walters ◽  
Chris Cannings
Keyword(s):  
Experimental Evidence ◽  
Genetic Drift ◽  
Finite Population ◽  
Selective Advantage ◽  
Indirect Selection ◽  
Small Populations ◽  
Finite Populations ◽  
Population Sizes ◽  
Population Recombination

AbstractIt is well known that an allele causing increased recombination is expected to proliferate as a result of genetic drift in a finite population undergoing selection, without requiring other mechanisms. This is supported by recent simulations apparently demonstrating that, in small populations, drift is more important than epistasis in increasing recombination, with this effect disappearing in larger finite populations. However, recent experimental evidence finds a greater advantage for recombination in larger populations. These results are reconciled by demonstrating through simulation without epistasis that for m loci recombination has an appreciable selective advantage over a range of population sizes (am, bm). bm increases steadily with m while am remains fairly static. Thus, however large the finite population, if selection acts on sufficiently many loci, an allele that increases recombination is selected for. We show that as selection acts on our finite population, recombination increases the variance in expected log fitness, causing indirect selection on a recombination-modifying locus. This effect is enhanced in those populations with more loci because the variance in phenotypic fitnesses in relation to the possible range will be smaller. Thus fixation of a particular haplotype is less likely to occur, increasing the advantage of recombination.

scholarly journals Testing temporal changes in allele frequencies: a simulation approach

2010 ◽  
Vol 92 (4) ◽  
pp. 309-320 ◽  
Author(s):  
EDSON SANDOVAL-CASTELLANOS
Keyword(s):  
Molecular Data ◽  
Temporal Changes ◽  
Allele Frequencies ◽  
Small Populations ◽  
Simulation Approach ◽  
Simulation Test ◽  
Agent Based ◽  
Binomial Sampling ◽  
Molecular Databases ◽  
Parameter Values

SummaryAnalysis of the temporal variation in allele frequencies is useful for studying microevolutionary processes. However, many statistical methods routinely used to test temporal changes in allele frequencies fail to establish a proper hypothesis or have theoretical or practical limitations. Here, a Bayesian statistical test is proposed in which the distribution of the distances among sampling frequencies is approached with computer simulations, and hypergeometric sampling is considered instead of binomial sampling. To validate the test and compare its performance with other tests, agent-based model simulations were run for a variety of scenarios, and two real molecular databases were analysed. The results showed that the simulation test (ST) maintained the significance value used (α=0·05) for a vast combination of parameter values, whereas other tests were sensitive to the effect of genetic drift or binomial sampling. The differences between binomial and hypergeometric sampling were more complex than expected, and a novel effect was described. This study suggests that the ST is especially useful for studies with small populations and many alleles, as in microsatellite or sequencing molecular data.

scholarly journals Two-dimensional IR spectroscopy of the anti-HIV agent KP1212 reveals protonated and neutral tautomers that influence pH-dependent mutagenicity

2015 ◽  
Vol 112 (11) ◽  
pp. 3229-3234 ◽  
Author(s):  
Chunte Sam Peng ◽  
Bogdan I. Fedeles ◽  
Vipender Singh ◽  
Deyu Li ◽  
Tiffany Amariuta ◽  
...  
Keyword(s):  
Ir Spectroscopy ◽  
Mutation Rates ◽  
Viral Population ◽  
Lethal Mutagenesis ◽  
2D Ir ◽  
Viral Mutation ◽  
Unique Shape ◽  
Ph Dependent ◽  
Mutagenic Property ◽  
Anti Hiv

Antiviral drugs designed to accelerate viral mutation rates can drive a viral population to extinction in a process called lethal mutagenesis. One such molecule is 5,6-dihydro-5-aza-2′-deoxycytidine (KP1212), a selective mutagen that induces A-to-G and G-to-A mutations in the genome of replicating HIV. The mutagenic property of KP1212 was hypothesized to originate from its amino–imino tautomerism, which would explain its ability to base pair with either G or A. To test the multiple tautomer hypothesis, we used 2D IR spectroscopy, which offers subpicosecond time resolution and structural sensitivity to distinguish among rapidly interconverting tautomers. We identified several KP1212 tautomers and found that >60% of neutral KP1212 is present in the enol–imino form. The abundant proportion of this traditionally rare tautomer offers a compelling structure-based mechanism for pairing with adenine. Additionally, the pKa of KP1212 was measured to be 7.0, meaning a substantial population of KP1212 is protonated at physiological pH. Furthermore, the mutagenicity of KP1212 was found to increase dramatically at pH <7, suggesting a significant biological role for the protonated KP1212 molecules. Overall, our data reveal that the bimodal mutagenic properties of KP1212 result from its unique shape shifting ability that utilizes both tautomerization and protonation.

scholarly journals Higher-fitness yeast genotypes are less robust to deleterious mutations

Science ◽  
2019 ◽  
Vol 366 (6464) ◽  
pp. 490-493 ◽  
Author(s):  
Milo S. Johnson ◽  
Alena Martsul ◽  
Sergey Kryazhimskiy ◽  
Michael M. Desai
Keyword(s):  
Second Order ◽  
Order Selection ◽  
Deleterious Mutations ◽  
Mutational Robustness ◽  
First Order ◽  
Fitness Effects ◽  
Yeast Strains ◽  
Selection For ◽  
Microbial Systems ◽  
Insertion Mutations

Natural selection drives populations toward higher fitness, but second-order selection for adaptability and mutational robustness can also influence evolution. In many microbial systems, diminishing-returns epistasis contributes to a tendency for more-fit genotypes to be less adaptable, but no analogous patterns for robustness are known. To understand how robustness varies across genotypes, we measure the fitness effects of hundreds of individual insertion mutations in a panel of yeast strains. We find that more-fit strains are less robust: They have distributions of fitness effects with lower mean and higher variance. These differences arise because many mutations have more strongly deleterious effects in faster-growing strains. This negative correlation between fitness and robustness implies that second-order selection for robustness will tend to conflict with first-order selection for fitness.

scholarly journals Changes in life history and population size can explain the relative neutral diversity levels on X and autosomes in extant human populations

2020 ◽  
Vol 117 (33) ◽  
pp. 20063-20069
Author(s):  
Guy Amster ◽  
David A. Murphy ◽  
William R. Milligan ◽  
Guy Sella
Keyword(s):  
Life History ◽  
Population Size ◽  
Mutation Rates ◽  
Human Populations ◽  
Effective Population ◽  
Mutation Bias ◽  
Female Ratio ◽  
Generation Times ◽  
Population Sizes ◽  
Male Mutation Bias

In human populations, the relative levels of neutral diversity on the X and autosomes differ markedly from each other and from the naïve theoretical expectation of 3/4. Here we propose an explanation for these differences based on new theory about the effects of sex-specific life history and given pedigree-based estimates of the dependence of human mutation rates on sex and age. We demonstrate that life history effects, particularly longer generation times in males than in females, are expected to have had multiple effects on human X-to-autosome (X:A) diversity ratios, as a result of male-biased mutation rates, the equilibrium X:A ratio of effective population sizes, and the differential responses to changes in population size. We also show that the standard approach of using divergence between species to correct for male mutation bias results in biased estimates of X:A effective population size ratios. We obtain alternative estimates using pedigree-based estimates of the male mutation bias, which reveal that X:A ratios of effective population sizes are considerably greater than previously appreciated. Finally, we find that the joint effects of historical changes in life history and population size can explain the observed X:A diversity ratios in extant human populations. Our results suggest that ancestral human populations were highly polygynous, that non-African populations experienced a substantial reduction in polygyny and/or increase in the male-to-female ratio of generation times around the Out-of-Africa bottleneck, and that current diversity levels were affected by fairly recent changes in sex-specific life history.

scholarly journals Inbreeding depression due to mildly deleterious mutations in finite populations: size does matter

2000 ◽  
Vol 75 (1) ◽  
pp. 75-81 ◽  
Author(s):  
THOMAS BATAILLON ◽  
MARK KIRKPATRICK
Keyword(s):  
Population Size ◽  
Inbreeding Depression ◽  
Deleterious Mutation ◽  
Large Population ◽  
Genetic Load ◽  
Breeding Systems ◽  
Deleterious Mutations ◽  
Single Locus Analysis ◽  
Population Sizes ◽  
Inbreeding Rate

We studied the effects of population size on the inbreeding depression and genetic load caused by deleterious mutations at a single locus. Analysis shows how the inbreeding depression decreases as population size becomes smaller and/or the rate of inbreeding increases. This pattern contrasts with that for the load, which increases as population size becomes smaller but decreases as inbreeding rate goes up. The depression and load both approach asymptotic limits when the population size becomes very large or very small. Numerical results show that the transition between the small and the large population regimes is quite rapid, and occurs largely over a range of population sizes that vary by a factor of 10. The effects of drift on inbreeding depression may bias some estimates of the genomic rate of deleterious mutation. These effects could also be important in the evolution of breeding systems in hermaphroditic organisms and in the conservation of endangered populations.

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