The Impact of Lethal Recessive Alleles on Bottlenecks with Implications for Conservation Genetics

2016 ◽  
Author(s):  
R. B. Campbell
Keyword(s):  
Large Population ◽  
Genetic Load ◽  
Ancestral Population ◽  
Deleterious Mutations ◽  
Recessive Mutations ◽  
Deleterious Alleles ◽  
Endangered Population ◽  
Population Breeding ◽  
The Cost ◽  
The Impact

AbstractWhen a bottleneck occurs, lethal recessive alleles from the ancestral population provide a genetic load. The purging of lethal recessive mutations may prolong the bottleneck, or even cause the population to become extinct. But the purging is of short duration, it will be over before near neutral deleterious alleles accumulate. Lethal recessive alleles from the parental population and near neutral deleterious mutations which occur during a bottleneck are temporally separated threats to the survival of a population. Breeding individuals from a large population into a small endangered population will provide the benefit of viable alleles to replace near neutral deleterious alleles but also the cost of lethal recessive mutations from the large population.

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.

scholarly journals Sex differences in deleterious genetic variants in a haplodiploid social insect

2021 ◽  
Author(s):  
Sara E. Miller ◽  
Michael J. Sheehan
Keyword(s):  
Genetic Load ◽  
Low Frequency ◽  
Paper Wasp ◽  
Deleterious Mutations ◽  
Wild Populations ◽  
Nonsense Mutations ◽  
Low Frequencies ◽  
Complete Dominance ◽  
Deleterious Alleles ◽  
Population Allele Frequency

AbstractDeleterious variants are selected against but can linger in populations at low frequencies for long periods of time, decreasing fitness and contributing to disease burden in humans and other species. Deleterious variants occur at low frequency but distinguishing deleterious variants from low frequency neutral variation is challenging based on population genetics data. As a result, we have little sense of the number and identity of deleterious variants in wild populations. For haplodiploid species, it has been hypothesized that deleterious alleles will be directly exposed to selection in haploid males, but selection can be masked in diploid females due to partial or complete dominance, resulting in more efficient purging of deleterious mutations in males. Therefore, comparisons of the differences between haploid and diploid genomes from the same population may be a useful method for inferring rare deleterious variants. This study provides the first formal test of this hypothesis. Using wild populations of Northern paper wasps (Polistes fuscatus), we find that males have fewer overall variants, and specifically fewer missense and nonsense variants, than females from the same population. Allele frequency differences are especially pronounced for rare missense and nonsense mutations and these differences lead to a lower genetic load in males than females. Based on these data we estimate that a large number of highly deleterious mutations are segregating in the paper wasp population. Stronger selection against deleterious alleles in haploid males may have implications for adaptation in other haplodiploid insects and provides evidence that wild populations harbor abundant deleterious variants.

scholarly journals Sexual selection and inbreeding: two efficient ways to limit the accumulation of deleterious mutations

2018 ◽  
Author(s):  
E. Noël ◽  
E. Fruitet ◽  
D. Lelaurin ◽  
N. Bonel ◽  
A. Ségard ◽  
...  
Keyword(s):  
Sexual Selection ◽  
Experimental Evolution ◽  
Genetic Load ◽  
Deleterious Mutations ◽  
Mutation Load ◽  
Male Function ◽  
Female Function ◽  
Deleterious Alleles ◽  
Self Fertilization ◽  
Male Specific

AbstractTheory and empirical data showed that two processes can boost selection against deleterious mutations, thus facilitating the purging of the mutation load: inbreeding, by exposing recessive deleterious alleles to selection in homozygous form, and sexual selection, by enhancing the relative reproductive success of males with small mutation loads. These processes tend to be mutually exclusive because sexual selection is reduced under mating systems that promote inbreeding, such as self-fertilization in hermaphrodites. We estimated the relative efficiency of inbreeding and sexual selection at purging the genetic load, using 50 generations of experimental evolution, in a hermaphroditic snail (Physa acuta). To this end, we generated lines that were exposed to various intensities of inbreeding, sexual selection (on the male function) and nonsexual selection (on the female function). We measured how these regimes affected the mutation load, quantified through the survival of outcrossed and selfed juveniles. We found that juvenile survival strongly decreased in outbred lines with reduced male selection, but not when female selection was relaxed, showing that male-specific sexual selection does purge deleterious mutations. However, in lines exposed to inbreeding, where sexual selection was also relaxed, survival did not decrease, and even increased for self-fertilized juveniles, showing that purging through inbreeding can compensate for the absence of sexual selection. Our results point to the further question of whether a mixed strategy combining the advantages of both mechanisms of genetic purging could be evolutionary stable.

scholarly journals Genomic signatures of inbreeding and genetic load in a threatened rattlesnake

2021 ◽  
Author(s):  
Alexander Ochoa ◽  
H. Lisle Gibbs
Keyword(s):  
Threatened Species ◽  
Empirical Studies ◽  
Genetic Load ◽  
Population History ◽  
Deleterious Mutations ◽  
Genetic Rescue ◽  
Isolated Populations ◽  
Genome Wide ◽  
The Impact

Theory predicts that threatened species living in small populations will experience high levels of inbreeding that will increase their negative genetic load but recent work suggests that the impact of load may be minimized by purging resulting from long term population bottlenecks. Empirical studies that examine this idea using genome-wide estimates of inbreeding and genetic load in threatened species are limited. Here we use genome resequencing data to compare levels of inbreeding, levels of genetic load and population history in threatened Eastern massasauga rattlesnakes (Sistrurus catenatus) which exist in small isolated populations and closely-related yet outbred Western massasauga rattlesnakes (S. tergeminus). In terms of inbreeding, S. catenatus genomes had a greater number of ROHs of varying sizes indicating sustained inbreeding through repeated bottlenecks when compared to S. tergeminus. At the species level, outbred S. tergeminus had higher genome-wide levels of genetic load in the form of greater numbers of derived deleterious mutations compared to S. catenatus presumably due to long-term purging of deleterious mutations in S. catenatus. In contrast, mutations that escaped the “drift sieve” and were polymorphic within S. catenatus populations were more abundant and more often found in homozygote genotypes than in S. tergeminus suggesting a reduced efficiency of purifying selection in smaller S. catenatus populations. Our results support an emerging idea that the historical demography of a threatened species has a significant impact on the type of genetic load present which impacts implementation of conservation actions such as genetic rescue.

scholarly journals Recent approaches into the genetic basis of inbreeding depression in plants

2003 ◽  
Vol 358 (1434) ◽  
pp. 1071-1084 ◽  
Author(s):  
David E. Carr ◽  
Michele R. Dudash
Keyword(s):  
Inbreeding Depression ◽  
Genetic Basis ◽  
Genetic Load ◽  
Strong Support ◽  
Major Effect ◽  
Inbred Lines ◽  
Recessive Mutations ◽  
Deleterious Alleles ◽  
Experimental Approaches ◽  
Marker Segregation Distortion

Predictions for the evolution of mating systems and genetic load vary, depending on the genetic basis of inbreeding depression (dominance versus overdominance, epistasis and the relative frequencies of genes of large and small effect). A distinction between the dominance and overdominance hypotheses is that deleterious recessive mutations should be purged in inbreeding populations. Comparative studies of populations differing in their level of inbreeding and experimental approaches that allow selection among inbred lines support this prediction. More direct biometric approaches provide strong support for the importance of partly recessive deleterious alleles. Investigators using molecular markers to study quantitative trait loci (QTL) often find support for overdominance, though pseudo–overdominance (deleterious alleles linked in repulsion) may bias this perception. QTL and biometric studies of inbred lines often find evidence for epistasis, which may also contribute to the perception of overdominance, though this may be because of the divergent lines initially crossed in QTL studies. Studies of marker segregation distortion commonly uncover genes of major effect on viability, but these have only minor contributions to inbreeding depression. Although considerable progress has been made in understanding the genetic basis of inbreeding depression, we feel that all three aspects merit more study in natural plant populations.

scholarly journals Obstruction of adaptation in diploids by recessive, strongly deleterious alleles

2015 ◽  
Vol 112 (20) ◽  
pp. E2658-E2666 ◽  
Author(s):  
Zoe June Assaf ◽  
Dmitri A. Petrov ◽  
Jamie R. Blundell
Keyword(s):  
Genetic Disorders ◽  
Natural Populations ◽  
Selective Advantage ◽  
Adaptive Mutation ◽  
Heterozygote Advantage ◽  
Deleterious Mutations ◽  
Beneficial Mutation ◽  
Recessive Mutations ◽  
Deleterious Alleles ◽  
Signature Of Selection

Recessive deleterious mutations are common, causing many genetic disorders in humans and producing inbreeding depression in the majority of sexually reproducing diploids. The abundance of recessive deleterious mutations in natural populations suggests they are likely to be present on a chromosome when a new adaptive mutation occurs, yet the dynamics of recessive deleterious hitchhikers and their impact on adaptation remains poorly understood. Here we model how a recessive deleterious mutation impacts the fate of a genetically linked dominant beneficial mutation. The frequency trajectory of the adaptive mutation in this case is dramatically altered and results in what we have termed a “staggered sweep.” It is named for its three-phased trajectory: (i) Initially, the two linked mutations have a selective advantage while rare and will increase in frequency together, then (ii), at higher frequencies, the recessive hitchhiker is exposed to selection and can cause a balanced state via heterozygote advantage (the staggered phase), and (iii) finally, if recombination unlinks the two mutations, then the beneficial mutation can complete the sweep to fixation. Using both analytics and simulations, we show that strongly deleterious recessive mutations can substantially decrease the probability of fixation for nearby beneficial mutations, thus creating zones in the genome where adaptation is suppressed. These mutations can also significantly prolong the number of generations a beneficial mutation takes to sweep to fixation, and cause the genomic signature of selection to resemble that of soft or partial sweeps. We show that recessive deleterious variation could impact adaptation in humans and Drosophila.

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 Estimates of genetic load in small populations suggest extensive purging of deleterious alleles

2019 ◽  
Author(s):  
Tom van der Valk ◽  
Marc de Manuel ◽  
Tomas Marques-Bonet ◽  
Katerina Guschanski
Keyword(s):  
Large Population ◽  
Genetic Load ◽  
Small Population ◽  
Small Populations ◽  
Population Declines ◽  
Current Conservation ◽  
Low Genetic Diversity ◽  
Deleterious Alleles ◽  
Declining Populations ◽  
Genetic Purging

AbstractDeclining populations are expected to experience negative genetic consequences of inbreeding, which over time can drive them to extinction. Yet, many species have survived in small populations for thousands of generations without apparent fitness effects, possibly due to genetic purging of partially deleterious recessive alleles in inbred populations. We estimate the abundance of deleterious alleles in a range of mammals and find that conversely to current conservation thinking species with historically small population size and low genetic diversity generally have lower genetic load compared to species with large population sizes. Rapid population declines will thus disproportionally affect species with high diversity, as they carry many deleterious alleles that can reach fixation before being removed by genetic purging.

scholarly journals The spatial Muller’s ratchet: surfing of deleterious mutations during range expansion

2019 ◽  
Author(s):  
Félix Foutel-Rodier ◽  
Alison Etheridge
Keyword(s):  
Population Size ◽  
Range Expansion ◽  
Allee Effect ◽  
Large Population ◽  
Small Population ◽  
Deleterious Mutations ◽  
Muller's Ratchet ◽  
Muller’S Ratchet ◽  
Expansion Load ◽  
The Impact

AbstractDuring a range expansion, deleterious mutations can “surf” on the colonisation front. The resultant decrease in fitness is known as expansion load. An Allee effect is known to reduce the loss of genetic diversity of expanding populations, by changing the nature of the expansion from “pulled” to “pushed”. We study the impact of an Allee effect on the formation of an expansion load with a new model, in which individuals have the genetic structure of a Muller’s ratchet. A key feature of Muller’s ratchet is that the population fatally accumulates deleterious mutations due to the stochastic loss of the fittest individuals, an event called a click of the ratchet. We observe fast clicks of the ratchet at the colonization front owing to small population size, followed by a slow fitness recovery due to migration of fit individuals from the bulk of the population, leading to a transient expansion load. For large population size, we are able to derive quantitative features of the expansion wave, such as the wave speed and the frequency of individuals carrying a given number of mutations. Using simulations, we show that the presence of an Allee effect reduces the rate at which clicks occur at the front, and thus reduces the expansion load.

scholarly journals Negative linkage disequilibrium between amino acid changing variants reveals interference among deleterious mutations in the human genome

2020 ◽  
Author(s):  
Jesse A. Garcia ◽  
Kirk E. Lohmueller
Keyword(s):  
Linkage Disequilibrium ◽  
Human Genome ◽  
Natural Populations ◽  
Physical Distance ◽  
Deleterious Mutations ◽  
High Coverage ◽  
Recessive Mutations ◽  
Deleterious Alleles ◽  
Genome Wide ◽  
Negative Epistasis

AbstractWhile there has been extensive work on patterns of linkage disequilibrium (LD) for neutral loci, the extent to which negative selection impacts LD is less clear. Forces like Hill-Robertson interference and negative epistasis are expected to lead to deleterious mutations being found on distinct haplotypes. However, the extent to which these forces depend on the selection and dominance coefficients of deleterious mutations and shape genome-wide patterns of LD in natural populations with complex demographic histories has not been tested. In this study, we first used forward-in-time simulations to generate predictions as to how selection impacts LD. Under models where deleterious mutations have additive effects on fitness, deleterious variants less than 10 kb apart tend to be carried on different haplotypes, generating an excess of negative LD relative to pairs of synonymous SNPs. In contrast, for recessive mutations, there is no consistent ordering of how selection coefficients affect r2 decay. We then examined empirical data of modern humans from the 1000 Genomes Project. LD between derived nonsynonymous SNPs is more negative compared to pairs of derived synonymous variants. This result holds when matching SNPs for frequency in the sample (allele count), physical distance, magnitude of background selection, and genetic distance between pairs of variants, suggesting that this result is not due to these potential confounding factors. Lastly, we introduce a new statistic HR(j) which allows us to detect interference using unphased genotypes. Application of this approach to high-coverage human genome sequences confirms our finding that deleterious alleles tend to be located on different haplotypes more often than are neutral alleles. Our findings suggest that either interference or negative epistasis plays a pervasive role in shaping patterns of LD between deleterious variants in the human genome, and consequently influencing genome-wide patterns of LD.

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