Does operational sex ratio influence relative strength of purging selection in males versus females?

According to theory, sexual selection in males may efficiently purge mutation load of sexual populations, reducing or fully compensating ‘the cost of males’. For this to occur, mutations not only need to be deleterious to both sexes, they also must affect males more than females. A frequently overlooked problem is that relative strength of selection on males versus females may vary between environments, with social conditions being particularly likely to affect selection in males and females differently. Here, we induced mutations in red flour beetles (Tribolium castaneum) and tested their effect in both sexes under three different operational sex ratios (1:2, 1:1 and 2:1). Induced mutations decreased fitness of both males and females, but their effect was not stronger in males. Surprisingly, operational sex ratio did not affect selection against deleterious mutations nor its relative strength in the sexes. Thus, our results show no support for the role of sexual selection in the evolutionary maintenance of sex.     

Genomic Consequences of Long-Term Population Decline in Brown Eared Pheasant

Population genetic theory and empirical evidence indicate that deleterious alleles can be purged in small populations. However, this viewpoint remains controversial. It is unclear whether natural selection is powerful enough to purge deleterious mutations when wild populations continue to decline. Pheasants are terrestrial birds facing a long-term risk of extinction as a result of anthropogenic perturbations and exploitation. Nevertheless, there are scant genomics resources available for conservation management and planning. Here, we analyzed comparative population genomic data for the three extant isolated populations of Brown eared pheasant (Crossoptilon mantchuricum) in China. We showed that C. mantchuricum has low genome-wide diversity and a contracting effective population size because of persistent declines over the past 100,000 years. We compared genome-wide variation in C. mantchuricum with that of its closely related sister species, the Blue eared pheasant (C. auritum) for which the conservation concern is low. There were detrimental genetic consequences across all C. mantchuricum genomes including extended runs of homozygous sequences, slow rates of linkage disequilibrium decay, excessive loss-of-function mutations, and loss of adaptive genetic diversity at the major histocompatibility complex region. To the best of our knowledge, this study is the first to perform a comprehensive conservation genomic analysis on this threatened pheasant species. Moreover, we demonstrated that natural selection may not suffice to purge deleterious mutations in wild populations undergoing long-term decline. The findings of this study could facilitate conservation planning for threatened species and help recover their population size.     

Investigation of deleterious effects of nsSNPs in the POT1 gene: a structural genomics-based approach to understand the mechanism of cancer development

Protection of telomere 1 (POT1) is one of the key components of shelterin complex, implicated in maintaining the telomere homeostasis, and thus stability of the eukaryotic genome. A large number of non-synonymous single nucleotide polymorphisms (nsSNPs) in the POT1 gene have been reported to cause varieties of human diseases, including cancer. In recent years, a number of mutations in POT1 has been markedly increased, and interpreting the effect of these large numbers of mutations to understand the mechanism of associated diseases seems impossible using experimental approaches. Herein, we employ varieties of computational methods such as PROVEAN, PolyPhen-2, SIFT, PoPMuSiC, SDM2, STRUM, and MAESTRO to identify the effects of 387 nsSNPs on the structure and function of POT1 protein. We have identified about 183 nsSNPs as deleterious and termed them as “high-confidence nsSNPs.” Distribution of these high-confidence nsSNPs demonstrates that the mutation in oligonucleotide binding domain 1 is highly deleterious (one in every three nsSNPs), and high-confidence nsSNPs show a strong correlation with residue conservation. The structure analysis provides a detailed insights into the structural changes occurred in consequence of conserved mutations which lead to the cancer progression. This study, for the first time, offers a newer prospective on the role of POT1 mutations on the structure, function, and their relation to associated diseases.     

Deleterious Mutations Accumulate Faster in Allopolyploid Than Diploid Cotton (Gossypium) and Unequally between Subgenomes

Whole-genome duplication (polyploidization) is among the most dramatic mutational processes in nature, so understanding how natural selection differs in polyploids relative to diploids is an important goal. Population genetics theory predicts that recessive deleterious mutations accumulate faster in allopolyploids than diploids due to the masking effect of redundant gene copies, but this prediction is hitherto unconfirmed. Here, we use the cotton genus (Gossypium), which contains seven allopolyploids derived from a single polyploidization event 1–2 Million years ago, to investigate deleterious mutation accumulation. We use two methods of identifying deleterious mutations at the nucleotide and amino acid level, along with whole-genome resequencing of 43 individuals spanning six allopolyploid species and their two diploid progenitors, to demonstrate that deleterious mutations accumulate faster in allopolyploids than in their diploid progenitors. We find that, unlike what would be expected under models of demographic changes alone, strongly deleterious mutations show the biggest difference between ploidy levels, and this effect diminishes for moderately and mildly deleterious mutations. We further show that the proportion of nonsynonymous mutations that are deleterious differs between the two coresident subgenomes in the allopolyploids, suggesting that homoeologous masking acts unequally between subgenomes. Our results provide a genome-wide perspective on classic notions of the significance of gene duplication that likely are broadly applicable to allopolyploids, with implications for our understanding of the evolutionary fate of deleterious mutations. Finally, we note that some measures of selection (e.g., dN/dS, π_N/π_S) may be biased when species of different ploidy levels are compared.     

Revisiting the notion of deleterious sweeps

It has previously been shown that, conditional on its fixation, the time to fixation of a semi-dominant deleterious autosomal mutation in a randomly mating population is the same as that of an advantageous mutation. This result implies that deleterious mutations could generate selective sweep-like effects. Although their fixation probabilities greatly differ, the much larger input of deleterious relative to beneficial mutations suggests that this phenomenon could be important. We here examine how the fixation of mildly deleterious mutations affects levels and patterns of polymorphism at linked sites—both in the presence and absence of interference amongst deleterious mutations—and how this class of sites may contribute to divergence between-populations and species. We find that, while deleterious fixations are unlikely to represent a significant proportion of outliers in polymorphism-based genomic scans within populations, minor shifts in the frequencies of deleterious mutations can influence the proportions of private variants and the value of F_ST after a recent population split. As sites subject to deleterious mutations are necessarily found in functional genomic regions, interpretations in terms of recurrent positive selection may require reconsideration.     

Transposon dynamics and the breeding system

The selfish DNA hypothesis predicts that natural selection is responsible for preventing the unregulated build up of transposable elements in organismal genomes. Accordingly, between-species differences in the strength and effectiveness of selection against transposons should be important in driving the evolution of transposon activity and abundance. We used a modeling approach to investigate how the rate of self-fertilization influences the population dynamics of transposable elements. Contrasting effects of the breeding system were observed under selection based on transposon disruption of gene function versus selection based on element-mediated ectopic exchange. This suggests that the comparison of TE copy number in organisms with different breeding systems may provide a test of the relative importance of these forces in regulating transposon multiplication. The effects of breeding system also interacted with population size, particularly when there was no element excision. The strength and effectiveness of selection against transposons was reflected not only in their equilibrium abundance, but also in the per-site element frequency of individual insertions and the coefficient of variation in copy number. These results are discussed in relation to evidence on transposon abundance available from the literature, and suggestions for future data collection. With their immense variety of breeding systems,plants will be extremely important for comparative studies and for sorting out the forces influencing...variation. This revised version was published online in July 2006 with corrections to the Cover Date.     

A comprehensive model of mutations affecting fitness and inferences for Arabidopsis thaliana

As the ultimate source of genetic variation, spontaneous mutation is essential to evolutionary change. Theoretical studies over several decades have revealed the dependence of evolutionary consequences of mutation on specific mutational properties, including genomic mutation rates, U, and the effects of newly arising mutations on individual fitness, s. The recent resurgence of empirical effort to infer these properties for diverse organisms has not achieved consensus. Estimates, which have been obtained by methods that assume mutations are unidirectional in their effects on fitness, are imprecise. Both because a general approach must allow for occurrence of fitness-enhancing mutations, even if these are rare, and because recent evidence demands it, we present a new method for inferring mutational parameters. For the distribution of mutational effects, we retain Keightley's assumption of the gamma distribution, to take advantage of the flexibility of its shape. Because the conventional gamma is one sided, restricting it to unidirectional effects, we include an additional parameter, rho, as an amount it is displaced from zero. Estimation is accomplished by Markov chain Monte Carlo maximum likelihood. Through a limited set of simulations, we verify the accuracy of this approach. We apply it to analyze data on two reproductive fitness components from a 17-generation mutation-accumulation study of a Columbia accession of Arabidopsis thaliana in which 40 lines sampled in three generations were assayed simultaneously. For these traits, U approximately/= 0.1-0.2, with distributions of mutational effects broadly spanning zero, such that roughly half the mutations reduce reproductive fitness. One evolutionary consequence of these results is lower extinction risks of small populations of A. thaliana than expected from the process of mutational meltdown. A comprehensive view of the evolutionary consequences of mutation will depend on quantitatively accounting for fitness-enhancing, as well as fitness-reducing, mutations.     

The conservation of redundancy in genetic systems: effects of sexual and asexual reproduction

The relationship between probability of survival and the number of deleterious mutations in the genome is investigated using three different models of highly redundant systems that interact with a threatening environment. Model one is a system that counters a potentially lethal infection; it has multiple identical components that act in sequence and in parallel. Model two has many different overlapping components that provide three-fold coverage of a large number of vital functions. The third model is based on statistical decision theory: an ideal detector, following an optimum decision strategy, makes crucial decisions in an uncertain world. The probability of a fatal error is reduced by a redundant sampling system, but the chance of error rises as the system is impaired by deleterious mutations. In all three cases the survival profile shows a synergistic pattern in that the probability of survival falls slowly and then more rapidly. This is different than the multiplicative or independent survival profile that is often used in mathematical models. It is suggested that a synergistic profile is a property of redundant systems. Model one is then used to study the conservation of redundancy during sexual and asexual reproduction. A unicellular haploid organism reproducing asexually retains redundancy when the mutation rate is very low (0001 per cell division), but tends to lose high levels of redundancy if the mutation rate is increased (001 to 01 per cell division). If a similar unicellular haploid organism has a sexual phase then redundancy is retained for mutation rates between 0001 and 01 per cell division. The sexual organism outgrows the asexual organism when the above mutation rates apply. If they compete for finite resources the asexual organism will be extinguished. Variants of the sexual organism with increased redundancy will outgrow those with lower levels of redundancy and the sexual process facilitates the evolution of more complex forms. There is a limit to the extent that complexity can be increased by increasing the size of the genome and in asexual organisms this leads to progressive accumulation of mutations with loss of redundancy and eventual extinction. If complexity is increased by using genes in new combinations, the asexual form can reach a stable equilibrium, although it is associated with some loss of redundancy. The sexual form, by comparison, can survive, with retention of redundancy, even if the mutation rate is above one per generation. The conservation and evolution of redundancy, which is essential for complexity, depends on the sexual process of reproduction.