Sex differences in deleterious mutational effects in D. melanogaster: combining quantitative and population genetic insights

Genetics ◽  
2021 ◽  
Author(s):  
Filip Ruzicka ◽  
Tim Connallon ◽  
Max Reuter
Keyword(s):  
Sex Differences ◽  
Population Genetic ◽  
Genetic Basis ◽  
Purifying Selection ◽  
Male Adult ◽  
Fitness Effects ◽  
Deleterious Alleles ◽  
Molecular Population Genetics ◽  
Selection For ◽  
Average Fitness

Abstract Fitness effects of deleterious mutations can differ between females and males due to: (i) sex differences in the strength of purifying selection; and (ii) sex differences in ploidy. Although sex differences in fitness effects have important broader implications (e.g., for the evolution of sex and lifespan), few studies have quantified their scope. Those that have belong to one of two distinct empirical traditions: (i) quantitative genetics, which focusses on multi-locus genetic variances in each sex, but is largely agnostic about their genetic basis; and (ii) molecular population genetics, which focusses on comparing autosomal and X-linked polymorphism, but is poorly suited for inferring contemporary sex differences. Here we combine both traditions to present a comprehensive analysis of female and male adult reproductive fitness among 202 outbred, laboratory-adapted, hemiclonal genomes of Drosophila melanogaster. While we find no clear evidence for sex differences in the strength of purifying selection, sex differences in ploidy generate multiple signals of enhanced purifying selection for X-linked loci. These signals are present in quantitative genetic metrics—i.e., a disproportionate contribution of the X to male (but not female) fitness variation—and population genetic metrics—i.e., steeper regressions of an allele’s average fitness effect on its frequency, and proportionally less nonsynonymous polymorphism on the X than autosomes. Fitting our data to models for both sets of metrics, we infer that deleterious alleles are partially recessive. Given the often-large gap between quantitative and population genetic estimates of evolutionary parameters, our study showcases the benefits of combining genomic and fitness data when estimating such parameters.

scholarly journals Sex differences in fitness and selection for centric fusions between sex-chromosomes and autosomes

1980 ◽  
Vol 35 (2) ◽  
pp. 205-214 ◽  
Author(s):  
D. Charlesworth ◽  
B. Charlesworth
Keyword(s):  
Sex Differences ◽  
Sex Difference ◽  
Sex Chromosomes ◽  
Initial Rate ◽  
Necessary Condition ◽  
Fitness Effects ◽  
Rate Of Increase ◽  
Computer Calculations ◽  
Selection For ◽  
Parameter Values

SUMMARYA model of centric fusions between the X or Y chromosome and an autosome carrying a selected locus is studied. It is assumed that fusions are not associated with any fitness effects, and that all chromosomes disjoin regularly from their homologues. It is shown that a necessary condition for the fusion to be favoured is that there is a selectively maintained sex difference in allele frequencies at the selected locus. If this condition is satisfied, the initial rate of increase of a rare Y-autosome fusion is about three times that of an X-autosome fusion, with the same parameter values. Computer calculations of the final equilibrium states reached by populations containing such fusions were done.

scholarly journals Background selection under evolving recombination rates

2021 ◽  
Author(s):  
Tom R Booker ◽  
Bret A Payseur ◽  
Anna Tigano
Keyword(s):  
Recombination Rate ◽  
Purifying Selection ◽  
Background Selection ◽  
Effective Population ◽  
Recombination Rates ◽  
Fitness Effects ◽  
Deleterious Alleles ◽  
Genome Wide ◽  
Modern House ◽  
Eukaryotic Genomes

Background selection (BGS), the effect that purifying selection exerts on sites linked to deleterious alleles, is expected to be ubiquitous across eukaryotic genomes. The effects of BGS reflect the interplay of the rates and fitness effects of deleterious mutations with recombination. A fundamental assumption of BGS models is that recombination rates are invariant over time. However, in some lineages recombination rates evolve rapidly, violating this central assumption. Here, we investigate how recombination rate evolution affects genetic variation under BGS. We show that recombination rate evolution modifies the effects of BGS in a manner similar to a localised change in the effective population size, potentially leading to an underestimation of the genome-wide effects of selection. Furthermore, we find evidence that recombination rate evolution in the ancestors of modern house mice may have impacted inferences of the genome-wide effects of selection in that species.

scholarly journals Review: Balancing Selection for Deleterious Alleles in Livestock

2021 ◽  
Vol 12 ◽  
Author(s):  
Martijn F. L. Derks ◽  
Marije Steensma
Keyword(s):  
Balancing Selection ◽  
Low Frequency ◽  
Purifying Selection ◽  
Population Level ◽  
Selection Strategy ◽  
Loss Of Function ◽  
Deleterious Alleles ◽  
Functional Consequences ◽  
Selection For ◽  
The Impact

Harmful alleles can be under balancing selection due to an interplay of artificial selection for the variant in heterozygotes and purifying selection against the variant in homozygotes. These pleiotropic variants can remain at moderate to high frequency expressing an advantage for favorable traits in heterozygotes, while harmful in homozygotes. The impact on the population and selection strength depends on the consequence of the variant both in heterozygotes and homozygotes. The deleterious phenotype expressed in homozygotes can range from early lethality to a slightly lower fitness in the population. In this review, we explore a range of causative variants under balancing selection including loss-of-function variation (i.e., frameshift, stop-gained variants) and regulatory variation (affecting gene expression). We report that harmful alleles often affect orthologous genes in different species, often influencing analogous traits. The recent discoveries are mainly driven by the increasing genomic and phenotypic resources in livestock populations. However, the low frequency and sometimes subtle effects in homozygotes prevent accurate mapping of such pleiotropic variants, which requires novel strategies to discover. After discovery, the selection strategy for deleterious variants under balancing selection is under debate, as variants can contribute to the heterosis effect in crossbred animals in various livestock species, compensating for the loss in purebred animals. Nevertheless, gene-assisted selection is a useful tool to decrease the frequency of the harmful allele in the population, if desired. Together, this review marks various deleterious variants under balancing selection and describing the functional consequences at the molecular, phenotypic, and population level, providing a resource for further study.

scholarly journals Sex differences in helping effort reveal the effect of future reproduction on cooperative behaviour in birds

2018 ◽  
Vol 285 (1885) ◽  
pp. 20181164 ◽  
Author(s):  
Philip A. Downing ◽  
Ashleigh S. Griffin ◽  
Charlie K. Cornwallis
Keyword(s):  
Sex Differences ◽  
Reproductive Success ◽  
Kin Selection ◽  
Cooperative Behaviour ◽  
The Future ◽  
Helping Behaviour ◽  
Future Reproduction ◽  
Selection For ◽  
Family Groups

The evolution of helping behaviour in species that breed cooperatively in family groups is typically attributed to kin selection alone. However, in many species, helpers go on to inherit breeding positions in their natal groups, but the extent to which this contributes to selection for helping is unclear as the future reproductive success of helpers is often unknown. To quantify the role of future reproduction in the evolution of helping, we compared the helping effort of female and male retained offspring across cooperative birds. The kin selected benefits of helping are equivalent between female and male helpers—they are equally related to the younger siblings they help raise—but the future reproductive benefits of helping differ because of sex differences in the likelihood of breeding in the natal group. We found that the sex which is more likely to breed in its natal group invests more in helping, suggesting that in addition to kin selection, helping in family groups is shaped by future reproduction.

scholarly journals Local genic base composition impacts protein production and cellular fitness

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4286 ◽  
Author(s):  
Erik M. Quandt ◽  
Charles C. Traverse ◽  
Howard Ochman
Keyword(s):  
Escherichia Coli ◽  
Base Composition ◽  
Protein Production ◽  
Purifying Selection ◽  
Specific Protein ◽  
Compositional Variation ◽  
Terminal Portion ◽  
A Genome ◽  
Selection For ◽  
Protein Feature

The maintenance of a G + C content that is higher than the mutational input to a genome provides support for the view that selection serves to increase G + C contents in bacteria. Recent experimental evidence fromEscherichia colidemonstrated that selection for increasing G + C content operates at the level of translation, but the precise mechanism by which this occurs is unknown. To determine the substrate of selection, we asked whether selection on G + C content acts across all sites within a gene or is confined to particular genic regions or nucleotide positions. We systematically altered the G + C contents of the GFP gene and assayed its effects on the fitness of strains harboring each variant. Fitness differences were attributable to the base compositional variation in the terminal portion of the gene, suggesting a connection to the folding of a specific protein feature. Variants containing sequence features that are thought to result in rapid translation, such as low G + C content and high levels of codon adaptation, displayed highly reduced growth rates. Taken together, our results show that purifying selection acting against A and T mutations most likely results from their tendency to increase the rate of translation, which can perturb the dynamics of protein folding.

Case studies in molecular population genetics

2019 ◽  
pp. 195-216
Author(s):  
Asher D. Cutter
Keyword(s):  
Population Genetics ◽  
Case Studies ◽  
Real World ◽  
Population Genetic ◽  
Genome Wide Association Study ◽  
Molecular Genetic ◽  
Raw Material ◽  
Genetic Analyses ◽  
Molecular Population Genetics ◽  
Population Genetic Analyses

Collections of DNA from nature for many individuals and loci give us the raw material for studying evolution at the molecular level. Chapter 9, “Case studies in molecular population genetics: genotype to phenotype to selection,” dives into several case studies of exciting real-world organisms that demonstrate the application from A to Z of the concepts developed throughout the book. It includes summaries of the natural context for each organism, ranging from armoring in fish (Eda, Pitx1) and color crypsis in mice (Mc1r) to butterfly flight ability (Pgi) and toxin metabolism in Drosophila fruit flies (Cyp6g1, Adh), then walks through the molecular data, their visualization, and their analysis. Complications and caveats to real-world analysis are discussed for how to identify demographic and selective effects in empirical datasets. The approaches include both candidate gene studies and genome scans, and show how different molecular population genetic analyses work in concert with one another. These population genetic analyses also can dovetail with functional molecular genetic experiments and with genetic mapping using crosses or genome-wide association study analysis. Chapter 9 ends by introducing a summary of several advanced topics in molecular population genetics, including concepts and tests for selection on standing variation, the genomic scale of data computation and evolutionary modelling, and connections to human evolution.

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.

Evidence for selection for the tyrosine-86 allele of the pfmdr 1 gene of Plasmodium falciparum by chloroquine and amodiaquine

Parasitology ◽  
1997 ◽  
Vol 114 (3) ◽  
pp. 205-211 ◽  
Author(s):  
M. T. DURAISINGH ◽  
C. J. DRAKELEY ◽  
O. MULLER ◽  
R. BAILEY ◽  
G. SNOUNOU ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Genetic Basis ◽  
Drug Trial ◽  
Enzyme Digestion ◽  
Restriction Enzyme Digestion ◽  
Blood Samples ◽  
Allelic Status ◽  
Group A ◽  
Selection For

The 4-aminoquinolines chloroquine (CQ) and amodiaquine (AM) were used to treat Gambian children with uncomplicated falciparum malaria in a randomized drug trial. Blood samples were taken immediately before treatment (day 0), and at day 7 and day 28 after treatment. Samples from those parasitologically positive at day 7 following treatment (‘early positives’) and those positive at day 28 but negative at day 7 (‘late positives’) have been studied by PCR followed by restriction enzyme digestion to determine the allelic status of the pfmdr 1 locus at the codon-86 position (asparagine or tyrosine), previously associated with resistance to CQ. A significantly higher prevalence of the tyr-86 allele was observed in samples taken immediately before treatment (day 0) in the early positives group when compared with the late positives group. This suggests the tyr-86 allele contributes to drug resistance in the early positives group. This association remained significant for both CQ and AM groups, implying a common genetic basis of resistance. Predominance of the allele at day 7 is consistent with a strong selection in the first week following treatment. In the late positives group, a significantly higher prevalence of the tyr-86 allele was observed in the samples at day 28 when compared with those at day 0, suggestive of selection during the period day 7 to day 28. Differences were observed in the extent of this selection in the CQ and AM groups. The samples were genotyped at 3 unlinked polymorphic loci. These analyses suggested that most parasites observed at day 7 were probably recrudescences whereas most of those at day 28 were reinfections.

Sign in / Sign up

Export Citation Format

Share Document