Genome analyses substantiate male mutation bias in many species

In many species the mutation rate is higher in males than in females, a phenomenon denoted as male mutation bias. This is often observed in animals where males produce many more sperm than females produce eggs, and is thought to result from differences in the number of replication-associated mutations accumulated in each sex. Thus, studies of male mutation bias have the capacity to reveal information about the replication-dependent or replication-independent nature of different mutations. The availability of whole genome sequences for many species, as well as for multiple individuals within a species, has opened the door to studying factors, both sequence-specific and those acting on the genome globally, that affect differences in mutation rates between males and females. Here, we assess the advantages that genomic sequences provide for studies of male mutation bias and general mutation mechanisms, discuss major challenges left unresolved, and speculate about the direction of future studies.     

Male-biased mutation, sex linkage, and the rate of adaptive evolution

An interaction between sex-linked inheritance and sex-biased mutation rates may affect the rate of adaptive evolution. Males have much higher mutation rates than females in several vertebrate and plant taxa. When evolutionary rates are limited by the supply of favorable new mutations, then genes will evolve faster when located on sex chromosomes that spend more time in males. For mutations with additive effects, Y-linked genes evolve fastest, followed by Z-linked genes, autosomal genes, X-linked genes, and finally W-linked and cytoplasmic genes. This ordering can change when mutations show dominance. The predicted differences in substitution rates may be detectable at the molecular level. Male-biased mutation could cause adaptive changes to accumulate more readily on certain kinds of chromosomes and favor animals with Z-W sex determination to have rapidly evolving male sexual displays.     

Low levels of nucleotide diversity in mammalian Y chromosomes

Sex chromosomes provide a useful context for the study of the relative importance of evolutionary forces affecting genetic diversity. The human Y chromosome shows levels of nucleotide diversity 20% that of autosomes, which is significantly less than expected when differences in effective population size and sex-specific mutation rates are taken into account. To study the generality of low levels of Y chromosome variability in mammalian genomes, we investigated nucleotide diversity in intron sequences of X (1.1-3.0 kb) and Y (0.7-3.5 kb) chromosome genes of five mammals: lynx, wolf, reindeer, cattle, and field vole. For all species, nucleotide diversity was found to be lower on Y than on X, with no segregating site observed in Y-linked sequences of lynx, reindeer, and cattle. For X chromosome sequences, nucleotide diversity was in the range of 1.6 x 10(-4) (lynx) to 8.0 x 10(-4) (field vole). When differences in effective population size and the extent of the male mutation bias were taken into account, all five species showed evidence of reduced levels of Y chromosome variability. Reduced levels of Y chromosome variability have also been observed in Drosophila and in plants, as well as in the female-specific W chromosome of birds. Among the different factors proposed to explain low levels of genetic variability in the sex-limited chromosome (Y/W), we note that selection is the only factor that is broadly applicable irrespective of mode of reproduction and whether there is male or female heterogamety.     

Postzygotic incompatibilities between the pupfishes, Cyprinodon elegans and Cyprinodon variegatus: hybrid male sterility and sex ratio bias

I examined the intrinsic postzygotic incompatibilities between two pupfishes, Cyprinodon elegans and Cyprinodon variegatus. Laboratory hybridization experiments revealed evidence of strong postzygotic isolation. Male hybrids have very low fertility, and the survival of backcrosses into C. elegans was substantially reduced. In addition, several crosses produced female-biased sex ratios. Crosses involving C. elegans females and C. variegatus males produced only females, and in backcrosses involving hybrid females and C. elegans males, males made up approximately 25% of the offspring. All other crosses produced approximately 50% males. These sex ratios could be explained by genetic incompatibilities that occur, at least in part, on sex chromosomes. Thus, these results provide strong albeit indirect evidence that pupfish have XY chromosomal sex determination. The results of this study provide insight on the evolution of reproductive isolating mechanisms, particularly the role of Haldane's rule and the 'faster-male' theory in taxa lacking well-differentiated sex chromosomes.     

The effect of sexual harassment on lethal mutation rate in female Drosophila melanogaster

The rate by which new mutations are introduced into a population may have far-reaching implications for processes at the population level. Theory assumes that all individuals within a population have the same mutation rate, but this assumption may not be true. Compared with individuals in high condition, those in poor condition may have fewer resources available to invest in DNA repair, resulting in elevated mutation rates. Alternatively, environmentally induced stress can result in increased investment in DNA repair at the expense of reproduction. Here, we directly test whether sexual harassment by males, known to reduce female condition, affects female capacity to alleviate DNA damage in Drosophila melanogaster fruitflies. Female gametes can repair double-strand DNA breaks in sperm, which allows manipulating mutation rate independently from female condition. We show that male harassment strongly not only reduces female fecundity, but also reduces the yield of dominant lethal mutations, supporting the hypothesis that stressed organisms invest relatively more in repair mechanisms. We discuss our results in the light of previous research and suggest that social effects such as density and courtship can play an important and underappreciated role in mediating condition-dependent mutation rate.     

The evolution of male genitalia: functional integration of genital sclerites in the dung beetle Onthophagus taurus

It is now widely recognized that sexual selection has been important in the rapid and divergent evolution of male genital morphology. However, distinguishing among putative mechanisms of sexual selection acting on male genital morphology represents a considerable challenge. Although there is growing evidence that variation in the size and/or shape of male genital structures can determine a male's success in gaining fertilizations, our knowledge of the functional morphology of male genitalia remains limited. Here we examine the functional morphology of genital sclerites that are known to influence paternity in the dung beetle Onthophagus taurus . We show that three of the sclerites form a functionally integrated unit that generates the tubular-shaped spermatophore and delivers its opening to the female's spermathecal duct. A fourth sclerite acts as a holdfast device during copulation. Our observations shed light on the mechanism by which these sclerites influence a male's paternity, and their patterns of phenotypic and genetic (co)variation.  © 2008 The Linnean Society of London, Biological Journal of the Linnean Society , 2008, 93 , 257–266.     

Operational sex ratio and density do not affect directional selection on male sexual ornaments and behavior

Demographic parameters including operational sex ratio (OSR) and population density may influence the opportunity for, and strength of sexual selection. Traditionally, male-biased OSRs and high population densities have been thought to increase the opportunity for sexual selection on male sexual traits due to increased male competition for mates. Recent experimental evidence, however, suggests that male-biased OSRs might reduce the opportunity for sexual selection due to increased sexual coercion experienced by females. How OSR, density, and any resultant changes in the opportunity for sexual selection actually affect selection on male sexual traits is unclear. In this study, we independently manipulated OSR and density in the guppy (Poecilia reticulata) without altering the number of males present. We recorded male and female behavior and used DNA microsatellite data to assign paternity to offspring and estimate male reproductive success. We then used linear selection analyses to examine the effects of OSR and density on directional sexual selection on male behavioral and morphological traits. We found that females were pursued more by males in male-biased treatments, despite no change in individual male behavior. There were no differences in sexual behavior experienced by females or performed by males in relation to density. Neither OSR nor density significantly altered the opportunity for sexual selection. Also, Although there was significant multivariate linear selection operating on males, neither OSR nor density altered the pattern of sexual selection on male traits. Our results suggest that differences in either OSR or density (independent of the number of males present) are unlikely to alter directional evolutionary change in male sexual traits.     

Accessory male investment can undermine the evolutionary stability of simultaneous hermaphroditism

Sex allocation (SA) models are traditionally based on the implicit assumption that hermaphroditism must meet criteria that make it stable against transition to dioecy. This, however, puts serious constraints on the adaptive values that SA can attain. A transition to gonochorism may, however, be impossible in many systems and therefore realized SA in hermaphrodites may not be limited by conditions that guarantee stability against dioecy. We here relax these conditions and explore how sexual selection on male accessory investments (e.g. a penis) that offer a paternity benefit affects the evolutionary stable strategy SA in outcrossing, simultaneous hermaphrodites. Across much of the parameter space, our model predicts male allocations well above 50 per cent. These predictions can help to explain apparently ‘maladaptive’ hermaphrodite systems.     

Condition‐dependent mutation rates and sexual selection

‘Good genes’ models of sexual selection show that females can gain indirect benefits for their offspring if male ornaments are condition‐dependent signals of genetic quality. Recurrent deleterious mutation is viewed as a major contributor to variance in genetic quality, and previous theoretical treatments of ‘good genes’ processes have assumed that the influx of new mutations is constant. I propose that this assumption is too simplistic, and that mutation rates vary in ways that are important for sexual selection. Recent data have shown that individuals in poor condition can have higher mutation rates, and I argue that if both male sexual ornaments and mutation rates are condition‐dependent, then females can use male ornamentation to evaluate their mate’s mutation rate. As most mutations are deleterious, females benefit from choosing well‐ornamented mates, as they are less likely to contribute germline‐derived mutations to offspring. I discuss some of the evolutionary ramifications of condition‐dependent mutation rates and sexual selection.     

Evolution of the isochore structure in the scale of chromosome: insight from the mutation bias and fixation bias

Following the development of reliable methods for inferring the direction of mutations of the single nucleotide polymorphism (SNP), and the revealing of the human isochore map, it has become possible to investigate the evolution of the isochore structure in a continuous region. In this study, the recent evolution of the isochore structure on human chromosome 18, as inferred from the SNP, was examined. A remarkable mutation bias was found, which was destroying the present isochore structure. However, a fixation bias contributed by the biased gene conversion (BGC) effect and a rising fixation probability of derived alleles with increasing GC content was extending the present isochore structure. Combining the two opposing processes, the old isochore structure was declining and a more homogenous isochore structure with higher GC content was being formed on the chromosome. During this process, both the CpG and genic sites, which were present in the isochore but were paid little attention to before, played an important role. In addition, the recombination was confirmed to promote the GC alleles fixed in the genome because of the BGC effect. For the first time, it was observed that with the occurrence of little recombination, AT alleles had the identical fixation probability with GC alleles in the recombination cold spots.     

Genic mutation rates in mammals: local similarity,chromosomal heterogeneity,and X-versus-autosome disparity

The reduction of mutation rates on the mammalian X chromosome relative to autosomes is most often explained in the literature as evidence of male-driven evolution. This hypothesis attributes lowered mutation rates on the X chromosome to the fact that this chromosome spends less time in the germline of males than in the germline of females. In contrast to this majority view, two articles argued that the patterns of mutation rates across chromosomes are inconsistent with male-driven evolution. One article reported a 40% reduction in synonymous substitution rates (Ks) for X-linked genes relative to autosomes in the mouse-rat lineage. The authors argued that this reduction is too dramatic to be explained by male-driven evolution and concluded that selection has systematically reduced mutation rate on the X chromosome to a level optimal for this male-hemizygous chromosome. More recently, a second article found that chromosomal mutation rates in both the human-mouse and mouse-rat lineages were so heterogeneous that the X chromosome was not an outlier. Here again, the authors argued that this is at odds with male-driven evolution and suggested that selection has modulated chromosomal mutation rates to locally optimal levels, thus extending the argument of the first mentioned article to include autosomes. Here, we reexamine these conclusions using mouse-rat and human-mouse coding-region data. We find a more modest reduction of Ks on the X chromosome, but our results contradict the finding that the X chromosome is not distinct from autosomes. Multiple statistical tests show that Ks rates on the X chromosome differ systematically from the autosomes in both lineages. We conclude that the moderate reduction of mutation rate on the X chromosome of both lineages is consistent with male-driven evolution; however, the large variance in mutation rates across chromosomes suggests that mutation rates are affected by additional factors besides male-driven evolution. Investigation of mutation rates by synteny reveals that synteny blocks, rather than entire chromosomes, might represent the unit of mutation rate variation.     

Substitution Rate Heterogeneity and the Male Mutation Bias

Germline mutation rates have been found to be higher in males than in females in many organisms, a likely consequence of cell division being more frequent in spermatogenesis than in oogenesis. If the majority of mutations are due to DNA replication error, the male-to-female mutation rate ratio (α_m) is expected to be similar to the ratio of the number of germ line cell divisions in males and females (c), an assumption that can be tested with proper estimates of α_m and c. α_m is usually estimated by comparing substitution rates in putatively neutral sequences on the sex chromosomes. However, substantial regional variation in substitution rates across chromosomes may bias estimates of α_m based on the substitution rates of short sequences. To investigate regional substitution rate variation, we estimated sequence divergence in 16 gametologous introns located on the Z and W chromosomes of five bird species of the order Galliformes. Intron ends and potentially conserved blocks were excluded to reduce the effect of using sequences subject to negative selection. We found significant substitution rate variation within Z chromosome (G₁₅ = 37.6, p = 0.0010) as well as within W chromosome introns (G₁₅ = 44.0, p = 0.0001). This heterogeneity also affected the estimates of α_m, which varied significantly, from 1.53 to 3.51, among the introns (ANOVA: F_13,14 =2.68, p = 0.04). Our results suggest the importance of using extensive data sets from several genomic regions to avoid the effects of regional mutation rate variation and to ensure accurate estimates of α_m. Electronic Supplementary Material Electronic Supplementary material is available for this article at and accessible for authorised users. [Reviewing Editor: Mr. Martin Kreitman] Nick G.C. Smith Deceased     

Juvenile infection and male display: testing the bright male hypothesis across individual life histories

Current tests of the bright male hypothesis focus on assaysof adult disease resistance and their relation to male traitdevelopment and female choice. We suggest that if parasiteshave significant harmful effects on juvenile stages of a host,then females selecting males that effectively signal juvenileparasite resistance may gain a significant "good genes" benefit.Currently, there is no information on juvenile and adult infectionor resistance in the same male and whether adult male displayssignal juvenile parasite resistance. In the present study, wemeasure infection of the ectoparasitic louse, Myrsidea ptilonorhynchi,in individual male satin bowerbirds (Ptilonorhynchus violaceus)both as juveniles and nine or more years later as adults. Wetest hypotheses that examine the role of juvenile parasite infectionin mediating sexual selection. We found that (1) juvenile infectionis higher than adult infection in the same individuals, (2)adult males able to hold display sites have lower juvenile infection,and (3) juvenile and adult infection in the same individualsare not significantly correlated. In addition, comparisons amonga larger set of individuals from a single year show that bloodand ectoparasite infections are highly correlated, and bothdecrease with male age and are inversely related to male courtshipsuccess. These results, combined with the evidence that femalesmate exclusively with bower-holding males support the hypothesisthat females use adult male display traits to identify maleswith a high level of juvenile disease resistance. We suggestthat effective tests of the bright male hypothesis should include(1) assessment of infection resistance in both subadult andadult life history stages, (2) tests of whether differencesin age-specific resistance are indicated in adult male displays,and (3) tests to determine if females attend to these traitsin mate choice. Although these requirements increase the difficultyof testing the bright male hypothesis, they are necessary fora more accurate assessment of the effects of parasites on maledisplay and female choice.     

人类基因组中突变对紧邻碱基的依赖性与重组率

减数分裂重组通过基因转变、碱基替换等方式影响基因组进化。紧邻碱基对突变偏好性有很强的影响,但该“紧邻碱基效应”如何随重组率变化有待深入研究。本文提出基于条件互信息(Conditional mutual information)量化突变对紧邻碱基依赖性的方法,并利用人类SNP等相关数据,分析重组率如何影响突变对紧邻碱基的依赖性。结果表明:在全基因组水平上, SNP位点上的突变对紧邻碱基的依赖性(即平均条件互信息)随着重组率的增加而增加;具体而言,当SNPs两侧碱基为A/G、C/G或C/T时,随着重组率的增加突变偏向性增强,但两侧碱基为A/A或T/T时,重组率对SNP突变偏向性产生抑制作用;另外,重组率越高,外显子与基因间区SNP的突变偏好性越强;而内含子区域SNP的突变偏好受到高重组率的抑制。结果有助于深入理解减数分裂重组如何影响基因组进化。     

Female-specific resource limitation does not make the opportunity for selection more female biased

Competition for limiting resources and stress can magnify variance in fitness and therefore selection. But even in a common environment, the strength of selection can differ across the sexes, as their fitness is often limited by different factors. Indeed, most taxa show stronger selection in males, a bias often ascribed to intense competition for access to mating partners. This sex bias could reverberate on many aspects of evolution, from speed of adaptation to genome evolution. It is unclear, however, whether stronger opportunity for selection in males is a pattern robust to sex-specific stress or resource limitation. We test this in the model species Callosobruchus maculatus by comparing female and male opportunity for selection (i) with and without limitation of quality oviposition sites, and (ii) under delayed age at oviposition. Decreasing the abundance of the resource key to females or increasing their reproductive age was challenging, as shown by a reduction in mean fitness, but opportunity for selection remained stronger in males across all treatments, and even more so when oviposition sites were limiting. This suggests that males remain the more variable sex independent of context, and that the opportunity for selection through males is indirectly affected by female-specific resource limitation.