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Deleterious or ‘disease-associated’ mutations are mutations that lead to disease with high phenotype penetrance: they are inherited in a simple Mendelian manner, or, in the case of cancer, accumulate in somatic cells leading directly to disease. However, in some cases, the amino acid that is substituted resulting in disease is the wild-type native residue in the functionally equivalent protein in another species. Such examples are known as ‘compensated pathogenic deviations’ (CPDs) because, somewhere in the second species, there must be compensatory mutations that allow the protein to function normally despite having a residue which would cause disease in the first species. Depending on the nature of the mutations, compensation can occur in the same protein, or in a different protein with which it interacts. In principle, compensation can be achieved by a single mutation (most probably structurally close to the CPD), or by the cumulative effect of several mutations. Although it is clear that these effects occur in proteins, compensatory mutations are also important in RNA potentially having an impact on disease. As a much simpler molecule, RNA provides an interesting model for understanding mechanisms of compensatory effects, both by looking at naturally occurring RNA molecules and as a means of computational simulation. This review surveys the rather limited literature that has explored these effects. Understanding the nature of CPDs is important in understanding traversal along fitness landscape valleys in evolution. It could also have applications in treating diseases that result from such mutations.

Insects constitute vital components of ecosystems. There is alarming evidence for global declines in insect species diversity, abundance, and biomass caused by anthropogenic drivers such as habitat degradation or loss, agricultural practices, climate change, and environmental pollution. This raises important concerns about human food security and ecosystem functionality and calls for more research to assess insect population trends and identify threatened species and the causes of declines to inform conservation strategies. Analysis of genetic diversity is a powerful tool to address these goals, but so far animal conservation genetics research has focused strongly on endangered vertebrates, devoting less attention to invertebrates, such as insects, that constitute most biodiversity. Insects' shorter generation times and larger population sizes likely necessitate different analytical methods and management strategies. The availability of high-quality reference genome assemblies enables population genomics to address several key issues. These include precise inference of past demographic fluctuations and recent declines, measurement of genetic load levels, delineation of evolutionarily significant units and cryptic species, and analysis of genetic adaptation to stressors. This enables identification of populations that are particularly vulnerable to future threats, considering their potential to adapt and evolve. We review the application of population genomics to insect conservation and the outlook for averting insect declines.

Recent phylogenetic analyses indicate that RNA virus populations carry a significant deleterious mutation load. This mutation load has the potential to shape patterns of adaptive evolution via genetic linkage to beneficial mutations. Here, we examine the effect of deleterious mutations on patterns of influenza A subtype H3N2's antigenic evolution in humans. By first analyzing simple models of influenza that incorporate a mutation load, we show that deleterious mutations, as expected, act to slow the virus's rate of antigenic evolution, while making it more punctuated in nature. These models further predict three distinct molecular pathways by which antigenic cluster transitions occur, and we find phylogenetic patterns consistent with each of these pathways in influenza virus sequences. Simulations of a more complex phylodynamic model further indicate that antigenic mutations act in concert with deleterious mutations to reproduce influenza's spindly hemagglutinin phylogeny, co-circulation of antigenic variants, and high annual attack rates.

The human diploid genome has approximately 40,000 functioning conserved genes distributed within 6 billion base pairs of DNA. Most individuals carry a few heterozygous deleterious mutations and this leads to an increased risk of recessive disease in the offspring of cousin unions. Rare recessive disease is more common in the children of cousin marriages than in the general population, even though less than 1% of marriages in the Western World are between first cousins. But more than 90% of the children of cousin marriages do not have recessive disease and are as healthy as the rest of the population. A mathematical model based on these observations generates simultaneous equations linking the mean number of deleterious mutations in the genome of adults (M), the mean number of new deleterious mutations arising in gametogenesis and passed to the next generation (N) and the number of genes in the human diploid genome (L). The best estimates are that M is less than 7 and N is approximately 1. The nature of meiosis indicates that deleterious mutations in zygotes will have a Poisson distribution with a mean of M + N. There must be strong selective pressure against zygotes at the upper end of the Poisson distribution otherwise the value of M would rise with each generation. It is suggested that this selection is based on synergistic interaction of heterozygous deleterious mutations acting in large complex highly redundant and robust genetic networks. To maintain the value of M in single figures over many thousands of generations means that the zygote loss must be of the order of 30%. Most of this loss will occur soon after conception but some will occur later; during fetal development, in infancy and even in childhood. Selection means genetic death and this is caused by disease to which the deleterious mutations predispose. In view of this genome sequencing should be undertaken in all infant deaths in which the cause of death is not ascertained by standard techniques.

The evolution of predominant self-fertilization from cross-fertilization in plants is accompanied by diverse changes to morphology, ecology and genetics, some of which likely result from regulatory changes in gene expression. We examined changes in gene expression during early stages in the transition to selfing in populations of animal-pollinated Eichhornia paniculata with contrasting mating patterns., We crossed plants from outcrossing and selfing populations and tested for the presence of allele-specific expression ( ASE) in floral buds and leaf tissue of F1 offspring, indicative of cis-regulatory changes., We identified 1365 genes exhibiting ASE in floral buds and leaf tissue. These genes preferentially expressed alleles from outcrossing parents. Moreover, we found evidence that genes exhibiting ASE had a greater nonsynonymous diversity compared to synonymous diversity in the selfing parents., Our results suggest that the transition from outcrossing to high rates of self-fertilization may have the potential to shape the cis-regulatory genomic landscape of angiosperm species, but that the changes in ASE may be moderate, particularly during the early stages of this transition. [ABSTRACT FROM AUTHOR]

Sexual reproduction leads to an alternation between haploid and diploid phases, whose relative length varies widely across taxa. Previous genetical models showed that diploid or haploid life cycles may be favored, depending on dominance interactions and on effective recombination rates. By contrast, niche differentiation between haploids and diploids may favor biphasic life cycles, in which development occurs in both phases. In this article, we explore the interplay between genetical and ecological factors, assuming that deleterious mutations affect the competitivity of individuals within their ecological niche and allowing different effects of mutations in haploids and diploids (including antagonistic selection). We show that selection on a modifier gene affecting the relative length of both phases can be decomposed into a direct selection term favoring the phase with the highest mean fitness (due to either ecological differences or differential effects of mutations) and an indirect selection term favoring the phase in which selection is more efficient. When deleterious alleles occur at many loci and in the presence of ecological differentiation between haploids and diploids, evolutionary branching often occurs and leads to the stable coexistence of alleles coding for haploid and diploid cycles, while temporal variations in niche sizes may stabilize biphasic cycles. [ABSTRACT FROM AUTHOR]

RNA viruses are the main source of emerging infectious diseases because of the evolutionary potential bestowed by their fast replication, large population sizes and high mutation and recombination rates. However, an equally important property, which is usually neglected, is the topography of the fitness landscape. How many fitness maxima exist and how well they are connected is especially interesting, as this determines the number of accessible evolutionary pathways. To address this question, we have reconstructed a region of the fitness landscape of tobacco etch potyvirus constituted by mutations observed during the experimental adaptation of the virus to the novel host Arabidopsis thaliana. Fitness was measured for many genotypes and showed the existence of multiple peaks and holes in the landscape. We found prevailing epistatic effects between mutations, with cases of reciprocal sign epistasis being common among pairs of mutations. We also found that high-order epistasis was as important as pairwise epistasis in their contribution to fitness. Therefore, results suggest that the landscape was rugged due to the existence of holes caused by lethal genotypes, that a very limited number of potential neutral paths exist and that it contained a single adaptive peak. [ABSTRACT FROM AUTHOR]

In many animals a small number of primordial germ cells (PGCs) are set aside early in development, mitosis and mitochondrial DNA syntheses are arrested, transcription is stopped or reduced, and the PGCs migrate later to the emerging gonads and become germ cells. What could be the evolutionary advantage of sequestering non-dividing PGCs early in development? A commonly cited advantage is a reduction in the number of new deleterious mutations that would occur if there were additional divisions in PGCs early in development. We would like to add to this advantage the fact that these additional mutations in PGCs give rise to germinal mosaics (i.e., premeiotic clusters of mutation) in multiple progeny of the same individual, thus having a larger detrimental effect on the evolutionary fitness of their carriers. Here, we reviewed published studies providing evidence that germinal mosaics of deleterious mutant alleles are not rare, occur for all types of genetic damage, and have been observed in all tested organisms and in nature. We propose the hypothesis that PGC sequestration during early animal development may have evolved in part in response to selection for preventing the occurrence of premeiotic clusters of deleterious mutant alleles, and describe a series of predictions that would allow the assessment of the potential role of germinal mosaics on the evolution of PGC sequestration. [ABSTRACT FROM AUTHOR]

The nature of selection acting on a population is in large measure determined by the distribution of fitness effects of new mutations. In this study, we use DNA sequences from four closely related clades of Saccharomyces paradoxus and Saccharomyces cerevisiae to identify and polarize new mutations and estimate their fitness effects. By progressively restricting the analyses to narrower categories of sites, we further seek to characterize sites with predictable mutational effects, that is, unconditionally deleterious, neutral or beneficial. Consistent with previous studies on S. paradoxus, we have failed to find evidence for mutations with beneficial effects, even in regions that were divergent in two outgroup clades, perhaps a consequence of the relatively unchallenged, predominantly asexual and highly inbred lifestyle of this species. On the other hand, there is abundant evidence of deleterious mutations, varying in severity of effect from strongly deleterious to very mild, particularly in regions conserved in the outgroup taxa, indicating a history of persistent purifying selection. Narrowing the analysis down to individual amino acids reduces further the range of effects: for example, mutations changing cysteine are predicted to be nearly always strongly deleterious, whereas those changing arginine, serine, and tyrosine are expected to be nearly neutral. The proportion of mutations with deleterious effects for a particular amino acid is correlated with long-term stasis of that amino acid among highly divergent sequences from a variety of organisms, showing that functionality of sites tends to persist through the diversification of clades and that our findings are also relevant to longer evolutionary times and other taxa. [ABSTRACT FROM AUTHOR]

Genetic diversity is a key parameter in population genetics and is important for understanding the process of evolution and for the development of appropriate conservation strategies. Recent advances in sequencing technology have enabled the measurement of genetic diversity of various organisms at the nucleotide level and on a genome-wide scale, yielding more precise estimates than were previously achievable. In this review, I have compiled and summarized the estimates of genetic diversity in humans and non-human primates based on recent genomewide studies. Although studies on population genetics demonstrated fluctuations in population sizes over time, general patterns have emerged. As shown previously, genetic diversity in humans is one of the lowest among primates; however, certain other primate species exhibit genetic diversity that is comparable to or even lower than that in humans. There exists greater than 10-fold variation in genetic diversity among primate species, and I found weak correlation with species fecundity but not with body or propagule size. I further discuss the potential evolutionary consequences of population size decline on the evolution of primate species. The level of genetic diversity negatively correlates with the ratio of nonsynonymous to synonymous polymorphisms in a population, suggesting that proportionally greater numbers of slightly deleterious mutations segregate in small rather than large populations. Although population size decline is likely to promote the fixation of slightly deleterious mutations, there are molecular mechanisms, such as compensatory mutations at various molecular levels, which may prevent fitness decline at the population level. The effects of slightly deleterious mutations from theoretical and empirical studies and their relevance to conservation biology are also discussed in this review. [ABSTRACT FROM AUTHOR]

Sexual reproduction is nearly universal among eukaryotes. Theory predicts that the rarity of asexual eukaryotic species is in part caused by accumulation of deleterious mutations and heightened extinction risk associated with suppressed recombination and segregation in asexual species. We tested this prediction with a large data set of 62 transcriptomes from 29 species in the plant genus Oenothera, spanning ten independent transitions between sexual and a functionally asexual genetic system called permanent translocation heterozygosity. Illumina short-read sequencing and de novo transcript assembly yielded an average of 16.4Mb of sequence per individual. Here, we show that functionally asexual species accumulate more deleterious mutations than sexual species using both population genomic and phylogenetic analysis. At an individual level, asexual species exhibited 1.8 higher heterozygosity than sexual species. Within species, we detected a higher proportion of nonsynonymous polymorphism relative to synonymous variation within asexual compared with sexual species, indicating reduced efficacy of purifying selection. Asexual species also exhibited a greater proportion of transcripts with premature stop codons. The increased proportion of nonsynonymous mutations was also positively correlated with divergence time between sexual and asexual species, consistent with Muller's ratchet. Between species, we detected repeated increases in the ratio of nonsynonymous to synonymous divergence in asexual species compared with sexually reproducing sister taxa, indicating increased accumulation of deleterious mutations. These results confirm that an important advantage of sex is that it facilitates selection against deleterious alleles, which might help to explain the dearth of extant asexual species. [ABSTRACT FROM AUTHOR]

The human diploid genome has approximately 40,000 functioning conserved genes distributed within 6 billion base pairs of DNA. Most individuals carry a few heterozygous deleterious mutations and this leads to an increased risk of recessive disease in the offspring of cousin unions. Rare recessive disease is more common in the children of cousin marriages than in the general population, even though <1% of marriages in theWestern World are between first cousins. But more than 90% of the children of cousin marriages do not have recessive disease and are as healthy as the rest of the population. A mathematical model based on these observations generates simultaneous equations linking the mean number of deleterious mutations in the genome of adults (M), the mean number of new deleterious mutations arising in gametogenesis and passed to the next generation (N) and the number of genes in the human diploid genome (L). The best estimates are that M is <7 and N is approximately 1. The nature of meiosis indicates that deleterious mutations in zygotes will have a Poisson distribution with a mean of MCN. There must be strong selective pressure against zygotes at the upper end of the Poisson distribution otherwise the value ofM would rise with each generation. It is suggested that this selection is based on synergistic interaction of heterozygous deleterious mutations acting in large complex highly redundant and robust genetic networks. To maintain the value of M in single figures over many thousands of generations means that the zygote loss must be of the order of 30%. Most of this loss will occur soon after conception but some will occur later; during fetal development, in infancy and even in childhood. Selection means genetic death and this is caused by disease to which the deleterious mutations predispose. In view of this genome sequencing should be undertaken in all infant deaths in which the cause of death is not ascertained by standard techniques. [ABSTRACT FROM AUTHOR]

In what types of environments should we expect to find strong inbreeding depression? Previous studies indicate that inbreeding depression, δ, is positively correlated with the stressfulness of the environment in which it is measured. However, it remains unclear why stress, per se, should increase δ. To our knowledge, only 'competitive stress' has a logical connection to δ. Through competition for resources, better quality (outbred) individuals make the environment worse for lower quality (inbred) individuals, accentuating the differences between them. For this reason, we expect inbreeding depression to be stronger in environments where the fitness of individuals is more sensitive to the presence of conspecifics (i.e., where fitness is more density dependent). Indeed, some studies suggest a role for competition within environments, but this idea has not been tested in the context of understanding variation in δ across environments. Using Drosophila melanogaster, we estimated δ for viability in 22 different environments. These environments were simultaneously characterized for (1) stressfulness and (2) density dependence. Although stress and density dependence are moderately correlated with each other, inbreeding depression is much more strongly correlated with density dependence. These results suggest that mean selection across the genome is stronger in environments where competition is intense, rather than in environments that are stressful for other reasons. [ABSTRACT FROM AUTHOR]

• The severity of SARS-CoV-2 infections is not related to a specific mutation. • A significant difference in the number and mutational patterns of viral quasispecies between the upper and the lower respiratory tract was observed. • An evidence of possible ongoing evolution in one of the gene loci that were crucial for the spillover to humans. • Genetic differentiation may impact immune response escape, tissue tropism, and pathogenicity. Studies are needed to better understand the genomic evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to describe viral quasispecies population of upper and lower respiratory tract by next-generation sequencing in patients admitted to intensive care unit. A deep sequencing of the S gene of SARS-CoV-2 from 109 clinical specimens, sampled from the upper respiratory tract (URT) and lower respiratory tract (LRT) of 77 patients was performed. A higher incidence of non-synonymous mutations and indels was observed in the LRT among minority variants. This might be explained by the ability of the virus to invade cells without interacting with ACE2 (e.g. exploiting macrophage phagocytosis). Minority variants are highly concentrated around the gene portion encoding for the Spike cleavage site, with a higher incidence in the URT; four mutations are highly recurring among samples and were found associated with the URT. Interestingly, 55.8% of minority variants detected in this locus were T>G and G>T transversions. Results from this study evidenced the presence of selective pressure and suggest that an evolutionary process is still ongoing in one of the crucial sites of spike protein associated with the spillover to humans. [ABSTRACT FROM AUTHOR]

Treatment of lung cancer is getting more personalized nowadays and medical practitioners are moving away from conventional histology-driven empirical treatments, platinum-based chemotherapy, and other invasive surgical resections and have started adopting alternate therapies in which therapeutic targets are patient's molecular oncogenic drivers. The aim of the current study is to extract meaningful information from the online somatic mutation data (retrieved from cBioPortal) of 16 most significantly mutated oncogenes in non-small-cell lung cancer (NSCLC), namely EGFR, NRAS, KRAS, HER2 (ERBB2), RET, MET, ROS1, FGFR1, BRAF, AKT1, MEK1 (MAP2K1), PIK3CA, PTEN, DDR2, LKB1 (STK11) and ALK, for improving our understanding of the pathobiology of the lung cancer that can aid decision-making on critical clinical and therapeutic considerations. Using an integrated approach comprising 4 steps, the oncogenic potential of 661 missense non-synonymous single nucleotide polymorphisms (nsSNPs) in 16 genes was ascertained using 2059 NSCLC (1575 lung adenocarcinomas, 484 lung squamous cell carcinomas) patients' online mutation data. The steps used comprise sequence/structure homology-based prediction, scoring of conservation of mutated residues and positions, prediction of resulting molecular and functional consequences using machine-learning and structure-guided approach. Out of a total of 661 nsSNPs analyzed, a set of 29 nsSNPs has been identified as conserved high confidence mutations in 10 of 16 genes relevant to the under study. Out of 29 conserved high confidence nsSNPs, 4 nsSNPs (EGFR N1094Y, BRAF M620I, DDR2 R307L, ALK P1350T) have been found to be putative novel rare genetic markers for NSCLC. The current study, the first of its kind, has provided a list of deleterious non-synonymous somatic mutations in a selected pool of oncogenes that can be considered as a promising target for future drug design and therapy for patients with lung adenocarcinomas and squamous cell carcinomas. • Deleterious non-synonymous somatic mutations associated with lung adenocarcinomas and squamous cell carcinomas are presented. [ABSTRACT FROM AUTHOR]

Selfing is assumed to reduce selection efficacy, especially purifying selection. This can be tested using molecular data, for example by comparing the Dn/ Ds ratio between selfing and outcrossing lineages. So far, little evidence of relaxed selection against weakly deleterious mutations (as inferred by a higher Dn/ Ds ratio) in selfers as compared to outcrossers has been found, contrary to the pattern often observed between asexual and sexual lineages. However, few groups have been studied to date. To further test this hypothesis, we compiled and analysed chloroplastic sequence data sets in several plant groups. We found a general trend towards relaxed selection in selfers in our data sets but with weak statistical support. Simulations suggested that the results were compatible with weak-to-moderate Dn/ Ds ratio differences in selfing lineages. Simple theoretical predictions also showed that the ability to detect relaxed selection in selfers could strongly depend on the distribution of the effects of deleterious mutations on fitness. Our results are compatible with a recent origin of selfing lineages whereby deleterious mutations potentially have a strong impact on population extinction or with a more ancient origin but without a marked effect of deleterious mutations on the extinction dynamics. [ABSTRACT FROM AUTHOR]

In diploid organisms, selfing reduces the efficiency of selection in removing deleterious mutations from a population. This need not be the case for all organisms. Some plants, for example, undergo an extreme form of selfing known as intragametophytic selfing, which immediately exposes all recessive deleterious mutations in a parental genome to selective purging. Here, we ask how effectively deleterious mutations are removed from such plants. Specifically, we study the extent to which deleterious mutations accumulate in a predominantly selfing and a predominantly outcrossing pair of moss species, using genome-wide transcriptome data. We find that the selfing species purge significantly more nonsynonymous mutations, as well as a greater proportion of radical amino acid changes which alter physicochemical properties of amino acids. Moreover, their purging of deleterious mutation is especially strong in conserved regions of protein-coding genes. Our observations show that selfing need not impede but can even accelerate the removal of deleterious mutations, and do so on a genome-wide scale. [ABSTRACT FROM PUBLISHER]

Deleterious mutations can reduce the fitness of crop varieties, which limits the plant breeding efficacy. While crop deleterious mutations have been extensively examined, most studies focused on one specific crop with different analyzing methods, which hinders unveiling shared genomic characteristics of deleterious mutations across diverse crops. Here we used standardized approaches to characterize the deleterious mutations in genomes of domesticated inbreeding (i.e., rice, soybean, and tomato) and clonally propagated crops (i.e., grape and pineapple). We found that deleterious mutations are commonly targeted by purifying selection, and are over-presented in a nearly fixed derived allele frequency in the course of plant domestication. Further, a generally negative correlation between genetic load and the artificial selection strength is observed. Importantly, we consistently uncovered the higher derived genomic heterozygosity for deleterious mutations compared to other genic variants. This study broadens our understanding of the evolution of deleterious mutations in plant genomes. • Plant deleterious mutations are commonly targeted by purifying selection. • Compared to synonymous mutations, deleterious ones are over-presented in fixed derived allele frequency during domestication. • Deleterious mutations have the highest genomic heterozygosity compared to other genic variants. • A negative correlation between genetic load and the strength of artificial selection is observed. [ABSTRACT FROM AUTHOR]

Estimating the extent of genetic differentiation between populations is an important measure in population genetics, ecology and evolutionary biology. The fixation index, or FST, is an important measure, which is routinely used to quantify this. Previous studies have shown that the FST estimated for selectively constrained regions was significantly lower than that estimated for neutral regions. By deriving the theoretical relationship between FST at neutral and constrained sites, we show that excess in the fraction of deleterious variations segregating within populations compared to those segregating between populations is the cause for the reduction in FST estimated at constrained sites. Using whole-genome data, our results revealed that the magnitude of reduction in FST estimates obtained for selectively constrained regions was much higher for distantly related populations compared to those estimated for closely related pairs. For example, the reduction was 47% for comparison between Europeans and Africans, 30% for the European and Asian comparison, 16% for the Northern and Southern European pair, and only 4% for the comparison involving two Southern European (Italian and Spanish) populations. Since deleterious variants are purged over time due to purifying selection, their contribution to the among-population diversity at constrained sites decreases with the increase in the divergence between populations. However, within-population diversities remain the same for all pairs compared; therefore, the FST estimated at constrained sites for distantly related populations are much smaller than those estimated for closely related populations. We obtained similar results when only the SNPs with similar allele frequencies at neutral and constrained sites were used. Our results suggest that the level of population divergence should be considered when comparing constrained site FST estimates from different pairs of populations. [ABSTRACT FROM AUTHOR]

Like other obligate asexuals, bdelloid rotifers are expected to suffer from degradation of their genomes through processes including the accumulation of deleterious mutations. However, sequence-based analyses in this regard remain inconclusive. Instead of looking for historical footprints of mutations in these ancient asexuals, we directly examined the susceptibility and ability to repair point mutations by the bdelloid Philodina roseola by inducing cyclobutane-pyrimidine dimers (CPDs) via exposure to UVB radiation (280-320nm). For comparison, we performed analogous experiments with the facultative asexual monogonont rotifer Brachionus rubens. Different strategies were found for the two species. Philodina roseola appeared to shield itself from CPD induction through uncharacterized UV-absorbing compounds and, except for the genome reconstruction that occurs after desiccation, was largely unable to repair UVB-induced damage. By contrast, B. rubens was more susceptible to UVB irradiation, but could repair all induced damage in ~2h. In addition, whereas UV irradiation had a significant negative impact on the reproductive output of P. roseola, and especially so after desiccation, that of B. rubens was unaffected. Although the strategy of P. roseola might suffice under natural conditions where UVB irradiation is less intense, the lack of any immediate CPD repair mechanisms in this species remains perplexing. It remains to be investigated how typical these results are for bdelloids as a group and therefore how reliant these animals are on desiccation-dependent genome repair to correct potential DNA damage given their obligate asexual lifestyle. [ABSTRACT FROM AUTHOR]

According to theoretical predictions sexual selection can reduce mutational load through male mating success. Males of good genetic quality should be more successful in matings, compared to the males of low genetic quality, thus in this way females can prevent deleterious alleles to be transmitted to the next generation. We tested this hypothesis through set up of two experimental groups from same genetic pool, where in one group genetic quality was manipulated by ionizing radiation. Within each group opportunity for choosing mates was imposed: males and females had no choice or had multiple choice. Mutational load was measured through the variability of different fitness components: fecundity and egg-to-adult viability. Our results indicate that sexual selection can reduce mutational load, only for fecundity. Group with the presence of female choice exhibited higher fecundity than group in which sexual selection was experimentally eliminated, but only in "irradiated" group. There was no overall difference in egg-to-adult viability between different sexual selection regimes in any of the group. It should be considered that sexual selection can cause sexual conflict, and potential opposite effects of sexual selection and sexual conflict on fitness. Genetic structure of populations, in terms of the level of mutational load, is an important factor which can determinate the role of sexual selection [ABSTRACT FROM AUTHOR]

Deleterious alleles are constantly introduced into populations due to mutation. In subdivided populations, the impact of these mutations depends on the strength of selection as well as the softness of selection, that is, the extent to which fitness is governed by local rather than global competition. It is widely appreciated that the intensity and type of competition will affect selection on deleterious mutations but most empirical work has focused solely on the effects of competition on selection strength. However, competition has rarely been studied in the context of selection 'softness' even though competition is at the conceptual root of soft selection. All other things being equal, theory predicts that inter- and intraspecific competitions have opposing effects on the softness of selection. Using Drosophila melanogaster, we estimated the strength and softness of selection in a 'baseline' competitive environment as well as two additional competitive environments characterized by either additional intra- or interspecific competitors. We found that competitive environment had little effect on the average strength of selection. While the softness of selection was affected by the type of competition, the direction of change varied across tests of different genes, contrary to expectation. Although the 'hard/soft' selection paradigm implicitly assumes that all individuals are equally sensitive to the local competitive environment, we found this not to be the case. Wild-type individuals were more sensitive to changes in the genetic quality of their local competitors than mutant individuals. [ABSTRACT FROM AUTHOR]

Recombination arrest between X and Y chromosomes, driven by sexually antagonistic genes, is expected to induce their progressive differentiation. However, in contrast to birds and mammals (which display the predicted pattern), most cold-blooded vertebrates have homomorphic sex chromosomes. Two main hypotheses have been proposed to account for this, namely high turnover rates of sex-determining systems and occasional XY recombination. Using individual-based simulations, we formalize the evolution of XY recombination (here mediated by sex reversal; the 'fountain-of-youth' model) under the contrasting forces of sexually antagonistic selection and deleterious mutations. The shift between the domains of elimination and accumulation occurs at much lower selection coefficients for the Y than for the X. In the absence of dosage compensation, mildly deleterious mutations accumulating on the Y depress male fitness, thereby providing incentives for XY recombination. Under our settings, this occurs via 'demasculinization' of the Y, allowing recombination in XY (sex-reversed) females. As we also show, this generates a conflict with the X, which coevolves to oppose sex reversal. The resulting rare events of XY sex reversal are enough to purge the Y from its load of deleterious mutations. Our results support the 'fountain of youth' as a plausible mechanism to account for the maintenance of sex-chromosome homomorphy. [ABSTRACT FROM AUTHOR]

Somatic mtDNA mutations have been reported in some human tumors, but their spectrum in different malignancies and their role in cancer development remain incompletely understood. Here, we describe the breadth of somatic and inherited mutations across the mitochondrial genome by sequence analyses of paired tumor and normal tissue samples from 226 individuals with five types of cancer using whole-genome data generated by The Cancer Genome Atlas Research Network. The frequencies of deleterious tumor-specific somatic mutations found in mtDNA varied across tumor types, ranging from 13% of glioblastomas to 63% of rectal adenocarcinomas. Compared with inherited mtDNA variants, somatic mtDNA mutations were enriched for nonsynonymous vs. synonymous changes (93 vs. 15; P < 2.2E-16) and were predicted to functionally impact the encoded protein. Somatic missense mutations in tumors were distributed uniformly among the mitochondrial protein genes, but 65% of somatic truncating mutations occurred in NADH dehydrogenase 5. Analysis of staging data in colon and rectal cancers revealed that the frequency of damaging mitochondrial mutations is the same in stages I and IV tumors. In summary, these data suggest that damaging somatic mtDNA mutations occur frequently (13-63%) in these five tumor types and likely confer a selective advantage in oncogenesis. [ABSTRACT FROM AUTHOR]