Searching for sex-reversals to explain population demography and the evolution of sex chromosomes.

Sex determination can be purely genetic (as in mammals and birds), purely environmental (as in many reptiles), or genetic but reversible by environmental factors during a sensitive period in life, as in many fish and amphibians (Wallace et al. 1999; Baroiller et al. 2009a; Stelkens & Wedekind 2010). Such environmental sex reversal (ESR) can be induced, for example, by temperature changes or by exposure to hormone-active substances. ESR has long been recognized as a means to produce more profitable single-sex cultures in fish farms (Cnaani & Levavi-Sivan 2009), but we know very little about its prevalence in the wild. Obviously, induced feminization or masculinization may immediately distort population sex ratios, and distorted sex ratios are indeed reported from some amphibian and fish populations (Olsen et al. 2006; Alho et al. 2008; Brykov et al. 2008). However, sex ratios can also be skewed by, for example, segregation distorters or sex-specific mortality. Demonstrating ESR in the wild therefore requires the identification of sex-linked genetic markers (in the absence of heteromorphic sex chromosomes) followed by comparison of genotypes and phenotypes, or experimental crosses with individuals who seem sex reversed, followed by sexing of offspring after rearing under non-ESR conditions and at low mortality. In this issue, Alho et al. (2010) investigate the role of ESR in the common frog (Rana temporaria) and a population that has a distorted adult sex ratio. They developed new sex-linked microsatellite markers and tested wild-caught male and female adults for potential mismatches between phenotype and genotype. They found a significant proportion of phenotypic males with a female genotype. This suggests environmental masculinization, here with a prevalence of 9%. The authors then tested whether XX males naturally reproduce with XX females. They collected egg clutches and found that some had indeed a primary sex ratio of 100% daughters. Other clutches seemed to result from multi-male fertilizations of which at least one male had the female genotype. These results suggest that sex-reversed individuals affect the sex ratio in the following generation. But how relevant is ESR if its prevalence is rather low, and what are the implications of successful reproduction of sex-reversed individuals in the wild?

Inbreeding and selection on sex ratio in the bark beetle Xylosandrus germanus.

ABSTRACT: BACKGROUND: Local Mate Competition (LMC) theory predicts a female should produce a more female-biased sex ratio if her sons compete with each other for mates. Because it provides quantitative predictions that can be experimentally tested, LMC is a textbook example of the predictive power of evolutionary theory. A limitation of many earlier studies in the field is that the population structure and mating system of the studied species are often estimated only indirectly. Here we use microsatellites to characterize the levels of inbreeding of the bark beetle Xylosandrus germanus, a species where the level of LMC is expected to be high. RESULTS: For three populations studied, genetic variation for our genetic markers was very low, indicative of an extremely high level of inbreeding (FIS = 0.88). There was also strong linkage disequilibrium between microsatellite loci and a very strong genetic differentiation between populations. The data suggest that matings among non-siblings are very rare (3%), although sex ratios from X. germanus in both the field and the laboratory have suggested more matings between non-sibs, and so less intense LMC. CONCLUSIONS: Our results confirm that caution is needed when inferring mating systems from sex ratio data, especially when a lack of biological detail means the use of overly simple forms of the model of interest.

Sex ratio and Wolbachia infection in the ant Formica exsecta.

Sex allocation data in social Hymenoptera provide some of the best tests of kin selection, parent-offspring conflict and sex ratio theories. However, these studies critically depend on controlling for confounding ecological factors and on identifying all parties that potentially manipulate colony sex ratio. It has been suggested that maternally inherited parasites may influence sex allocation in social Hymenoptera. If the parasites can influence sex allocation, infected colonies are predicted to invest more resources in females than non-infected colonies, because the parasites are transmitted through females but not males. Prime candidates for such sex ratio manipulation are Wolbachia, because these cytoplasmically transmitted bacteria have been shown to affect the sex ratio of host arthropods by cytoplasmic incompatibility, parthenogenesis, male-killing and feminization. In this study, we tested whether Wolbachia infection is associated with colony sex ratio in two populations of the ant Formica exsecta that have been the subject of extensive sex ratio studies. In these populations colonies specialize in the production of one sex or the other. We found that almost all F. exsecta colonies in both populations are infected with Wolbachia. However, in neither population did we find a significant association in the predicted direction between the prevalence of Wolbachia and colony sex ratio. In particular, colonies with a higher proportion of infected workers did not produce more females. Hence, we conclude that Wolbachia does not seem to alter the sex ratio of its hosts as a means to increase transmission rate in these two populations of ants.

Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism.

Several observations support the hypothesis that differences in synaptic and regional cerebral plasticity between the sexes account for the high ratio of males to females in autism. First, males are more susceptible than females to perturbations in genes involved in synaptic plasticity. Second, sex-related differences in non-autistic brain structure and function are observed in highly variable regions, namely, the heteromodal associative cortices, and overlap with structural particularities and enhanced activity of perceptual associative regions in autistic individuals. Finally, functional cortical reallocations following brain lesions in non-autistic adults (for example, traumatic brain injury, multiple sclerosis) are sex-dependent. Interactions between genetic sex and hormones may therefore result in higher synaptic and consecutively regional plasticity in perceptual brain areas in males than in females. The onset of autism may largely involve mutations altering synaptic plasticity that create a plastic reaction affecting the most variable and sexually dimorphic brain regions. The sex ratio bias in autism may arise because males have a lower threshold than females for the development of this plastic reaction following a genetic or environmental event.

Inconsistency between different measures of sexual selection.

Measuring the intensity of sexual selection is of fundamental importance to the study of sexual dimorphism, population dynamics, and speciation. Several indices, pools of individuals, and fitness proxies are used in the literature, yet their relative performances are strongly debated. Using 12 independent common lizard populations, we manipulated the adult sex ratio, a potentially important determinant of the intensity of sexual selection at a particular time and place. We investigated differences in the intensity of sexual selection, as estimated using three standard indices of sexual selection-the standardized selection gradient (β'), the opportunity of selection (I), and the Bateman gradient (βss)--calculated for different pools of individuals and different fitness proxies. We show that results based on estimates of I were the opposite of those derived from the other indices, whereas results based on estimates of β' were consistent with predictions derived from knowledge about the species' mating system. In addition, our estimates of the strength and direction of sexual selection depended on both the fitness proxy used and the pool of individuals included in the analysis. These observations demonstrate inconsistencies in distinct measures of sexual selection and underscore the need for caution when comparing studies and species.

Low Y chromosome variation in Saudi-Arabian hamadryas baboons (Papio hamadryas hamadryas).

It is important to characterise the amount of variation on the mammalian Y chromosome in order to assess its potential for use in evolutionary studies. We report very low levels of polymorphism on the Y chromosome of Saudi-Arabian hamadryas baboons, Papio hamadryas hamadryas. We found no segregating sites on the Y, despite sequence analysis of 3 kb noncontiguous intron sequence in 16 males with divergent autosomal microsatellite genotypes, and a further analysis of 1.1 kb intron sequence in 97 males from four populations by SSCP. In addition, we tested seven human-derived Y-linked microsatellites in baboons. Only four of these loci were male-specific and only one was polymorphic in our 97 male sample set. Polymorphism on the Y chromosome of Arabian hamadryas appears to be low compared to other primate species for which data are available (eg humans, chimpanzees and bonobos). Low effective population size (Ne) of paternal genes due to polygyny and female-biased adult sex ratio is a potential reason for low Y chromosome variation in this species. However, low Ne for the Y should be counterbalanced to some extent by the species' atypical pattern of male philopatry and female-biased dispersal. Allelic richness averaged over seven loci was not significantly different between an African and an Arabian population, suggesting that loss of variation during the colonisation of Arabia does not explain low Y variation. Finally, in the absence of nucleotide polymorphism, it is unclear to what extent selection could be responsible for low Y variation in this species.

Conflict over multiple-partner mating between males and females of the polygynandrous common lizards.

The optimal number of mate partners for females rarely coincides with that for males, leading to a potential sexual conflict over multiple-partner mating. This suggests that the population sex ratio may affect multiple-partner mating and thus multiple paternity. We investigate the relationship between multiple paternity and the population sex ratio in the polygynandrous common lizard (Lacerta vivipara). In six populations the adult sex ratio was biased toward males, and in another six populations the adult sex ratio was biased toward females, the latter corresponding to the average adult sex ratio encountered in natural populations. In males the frequency and the degree of polygyny were lower in male-biased populations, as expected if competition among males determines polygyny. In females the frequency of polyandry was not different between treatments, and polyandrous females produced larger clutches, suggesting that polyandry might be adaptive. However, in male-biased populations females suffered from reduced reproductive success compared to female-biased populations, and the number of mate partners increased with female body size in polyandrous females. Polyandrous females of male-biased populations showed disproportionately more mating scars, indicating that polyandrous females of male-biased populations had more interactions with males and suggesting that the degree of multiple paternity is controlled by male sexual harassment. Our results thus imply that polyandry may be hierarchically controlled, with females controlling when to mate with multiple partners and male sexual harassment being a proximate determinant of the degree of multiple paternity. The results are also consistent with a sexual conflict in which male behaviors are harmful to females.

Sex differentials in Swiss cancer mortality.

Swiss national cancer mortality statistics from 1951 to 1984 and survival rates from the Vaud Cancer Registry datafile over the period 1974-1980 were considered in terms of sex ratios. Overall age-standardized cancer mortality for population aged 35-64 showed only a moderate decline in males (from 230 to 221/100,000), but a substantial one in females (from 191 to 152/100,000). Mortality from most cancer sites (except gallbladder and thyroid) was persistently higher in males, the male/female ratio ranging between 1.2 for intestines, skin, brain and lympho-reticular neoplasms to about 2 for stomach or pancreas, up to 7-10 for lung and cancers related to tobacco and alcohol (mouth or pharynx, oesophagus). The sex ratio for lung cancer increased between the early 1950's and the mid 1960's, but noticeably declined thereafter, probably reflecting trends in smoking prevalence among subsequent generations of Swiss males and females. Less obvious is the substantial increase in the sex ratio for liver cancer (from 1.6 to 5.7), which was evident in younger middle age, too. Population-based cancer survival statistics indicated that for most common sites rates were appreciably higher in females than in males. Thus, better survival explains part of the advantage in cancer mortality for women. This can be related to earlier diagnosis, better compliance or responsiveness to treatment, although there is no obvious single interpretation for this generalized more favourable pattern in females.

Sex differences in lipid and glucose kinetics after ingestion of an acute oral fructose load.

The increase in VLDL TAG concentration after ingestion of a high-fructose diet is more pronounced in men than in pre-menopausal women. We hypothesised that this may be due to a lower fructose-induced stimulation of de novo lipogenesis (DNL) in pre-menopausal women. To evaluate this hypothesis, nine healthy male and nine healthy female subjects were studied after ingestion of oral loads of fructose enriched with 13C6 fructose. Incorporation of 13C into breath CO2, plasma glucose and plasma VLDL palmitate was monitored to evaluate total fructose oxidation, gluconeogenesis and hepatic DNL, respectively. Substrate oxidation was assessed by indirect calorimetry. After 13C fructose ingestion, 44.0 (sd 3.2)% of labelled carbons were recovered in plasma glucose in males v. 41.9 (sd 2.3)% in females (NS), and 42.9 (sd 3.7)% of labelled carbons were recovered in breath CO2 in males v. 43.0 (sd 4.5)% in females (NS), indicating similar gluconeogenesis from fructose and total fructose oxidation in males and females. The area under the curve for 13C VLDL palmitate tracer-to-tracee ratio was four times lower in females (P < 0.05), indicating a lower DNL. Furthermore, lipid oxidation was significantly suppressed in males (by 16.4 (sd 5.2), P < 0.05), but it was not suppressed in females ( -1.3 (sd 4.7)%). These results support the hypothesis that females may be protected against fructose-induced hypertriglyceridaemia because of a lower stimulation of DNL and a lower suppression of lipid oxidation.

On the maintenance of sex-chromosome polymorphism by sex-antagonistic selection

Complex sex-determination systems are a priori unstable and require specific selective forces for their maintenance. Analytical derivations have suggested that sex-antagonistic selection may play such a role, but this assumed absence of recombination between the sex-determining and sex-antagonistic genes. Using individual-based simulations, and focusing on the sex chromosome and coloration polymorphisms of platy fishes as a case study, we show that the conditions for polymorphism maintenance induce female-biases in primary sex ratios, so that sex-ratio selection makes the system collapse towards male- or female heterogamety as soon as recombinant genotypes appear. However, a polymorphism can still be maintained under scenarios comprising strong sexual selection against dull males, mild natural selection against bright females, and low recombination rates. Though such conditions are plausibly met in natural populations of fishes harbouring such polymorphisms, quantitative empirical evaluations are required to properly test whether sex-antagonistic selection is a causal agent, or if other selective processes are required (such as local mate competition favouring female biased sex ratios).

Split sex ratios in the social Hymenoptera: a meta-analysis

The study of sex allocation in social Hymenoptera (ants, bees, and wasps) provides an excellent opportunity for testing kin-selection theory and studying conflict resolution. A queen-worker conflict over sex allocation is expected because workers are more related to sisters than to brothers, whereas queens are equally related to daughters and sons. If workers fully control sex allocation, split sex ratio theory predicts that colonies with relatively high or low relatedness asymmetry (the relatedness of workers to females divided by the relatedness of workers to males) should specialize in females or males, respectively. We performed a meta-analysis to assess the magnitude of adaptive sex allocation biasing by workers and degree of support for split sex ratio theory in the social Hymenoptera. Overall, variation in relatedness asymmetry (due to mate number or queen replacement) and variation in queen number (which also affects relatedness asymmetry in some conditions) explained 20.9% and 5% of the variance in sex allocation among colonies, respectively. These results show that workers often bias colony sex allocation in their favor as predicted by split sex ratio theory, even if their control is incomplete and a large part of the variation among colonies has other causes. The explanatory power of split sex ratio theory was close to that of local mate competition and local resource competition in the few species of social Hymenoptera where these factors apply. Hence, three of the most successful theories explaining quantitative variation in sex allocation are based on kin selection.

Testing kin selection with sex allocation data in eusocial hymenoptera

Sex allocation data in eusocial Hymenoptera (ants, bees and wasps) provide an excellent opportunity to assess the effectiveness of kin selection, because queens and workers differ in their relatedness to females and males. The first studies on sex allocation in eusocial Hymenoptera compared population sex investment ratios across species. Female-biased investment in monogyne (= with single-queen colonies) populations of ants suggested that workers manipulate sex allocation according to their higher relatedness to females than males (relatedness asymmetry). However, several factors may confound these comparisons across species. First, variation in relatedness asymmetry is typically associated with major changes in breeding system and life history that may also affect sex allocation. Secondly, the relative cost of females and males is difficult to estimate across sexually dimorphic taxa, such as ants. Thirdly, each species in the comparison may not represent an independent data point, because of phylogenetic relationships among species. Recently, stronger evidence that workers control sex allocation has been provided by intraspecific studies of sex ratio variation across colonies. In several species of eusocial Hymenoptera, colonies with high relatedness asymmetry produced mostly females, in contrast to colonies with low relatedness asymmetry which produced mostly males. Additional signs of worker control were found by investigating proximate mechanisms of sex ratio manipulation in ants and wasps. However, worker control is not always effective, and further manipulative experiments will be needed to disentangle the multiple evolutionary factors and processes affecting sex allocation in eusocial Hymenoptera.

Invasion and fixation of sex-reversal genes.

We simulated a meta-population with random dispersal among demes but local mating within demes to investigate conditions under which a dominant female-determining gene W, with no individual selection advantage, can invade and become fixed in females, changing the population from male to female heterogamety. Starting with one mutant W in a single deme, the interaction of sex ratio selection and random genetic drift causes W to be fixed among females more often than a comparable neutral mutation with no influence on sex determination, even when YY males have slightly reduced viability. Meta-population structure and interdeme selection can also favour the fixation of W. The reverse transition from female to male heterogamety can also occur with higher probability than for a comparable neutral mutation. These results help to explain the involvement of sex-determining genes in the evolution of sex chromosomes and in sexual selection and speciation.

Regional variation in sex ratios and sex allocation in androdioecious Mercurialis annua.

In androdioecious metapopulations, where males co-occur with hermaphrodites, the absence of males from certain populations or regions may be explained by locally high selfing rates, high hermaphrodite outcross siring success (e.g. due to high pollen production by hermaphrodites), or to stochastic processes (e.g. the failure of males to invade populations or regions following colonization or range expansion by hermaphrodites). In the Iberian Peninsula and Morocco, the presence of males with hermaphrodites in the wind-pollinated androdioecious plant Mercurialis annua (Euphorbiaceae) varies both among populations within relatively small regions and among regions, with some regions lacking males from all populations. The species is known to have expanded its range into the Iberian Peninsula from a southern refugium. To account for variation in male presence in M. annua, we test the following hypotheses: (1) that males are absent in areas where plant densities are lower, because selfing rates should be correspondingly higher; (2) that males are absent in areas where hermaphrodites produce more pollen; and (3) that males are absent in areas where there is an elevated proportion of populations in which plant density and hermaphrodite pollen production disfavour their invasion. We found support for predictions two and three in Morocco (the putative Pleistocene refugium for M. annua) but no support for any hypothesis in Iberia (the expanded range). Our results are partially consistent with a hypothesis of sex-allocation equilibrium for populations in Morocco; in Iberia, the absence of males from large geographical regions is more consistent with a model of sex-ratio evolution in a metapopulation with recurrent population turnover. Our study points to the role of both frequency-dependent selection and contingencies imposed by colonization during range expansions and in metapopulations.

Introduction of Trojan sex chromosomes to boost population growth.

Conservation programs that deal with small or declining populations often aim at a rapid increase of population size to above-critical levels in order to avoid the negative effects of demographic stochasticity and genetic problems like inbreeding depression, fixation of deleterious alleles, or a general loss of genetic variability and hence of evolutionary potential. In some situations, population growth is determined by the number of females available for reproduction, and manipulation of family sex ratios towards more daughters has beneficial effects. If sex determination is predominantly genetic but environmentally reversible, as is the case in many amphibia, reptiles, and fish, Trojan sex chromosomes could be introduced into populations in order to change sex ratios towards more females. We analyse the possible consequences for the introduction of XX-males (XX individuals that have been changed to phenotypic males in a XY/XX sex determination system) and ZW males, WW males, or WW females (in a ZZ/ZW sex determination system). We find that the introduction of WW individuals can be most effective for an increase of population growth, especially if the induced sex change has little or no effect on viability.