Genetic sex determination, i. e. the determination of sexual phenotypes by the effect of sex-determining genes, is found in the majority of vertebrates. Sex determination genes have evolved multiple times independently and can be located on different chromosomes. Depending on whether the presence of the sex determining region (SDR) determines female or male sex, genetic systems of sex determination are called ZW or XY systems respectively and the sex which is heterozygous for the SDR is called the heterogametic sex. Lower fitness in the heterogametic sex has long been observed in interspecific hybrids in a wide range of animal and even plant species, an observation called Haldane’s rule. In this paper the authors find a similar pattern in (non-hybrid) tetrapod species: by comparing the adult sex ratio in XY and ZW systems in 344 tetrapod species, they find that the ASR is skewed towards the homogametic sex (towards females in an XY system and towards males in a ZW system).
This observation is based on a dataset containing known genetic sex determination systems and adult sex ratios (ASRs) of species across the vertebrate phylogeny. Within amphibians and reptiles (in which both XY and ZW systems are found), the authors show that ASRs in ZW systems are significantly more male biased than in XY systems and that the proportion of species with male-biased ASRs is greater in ZW than in XY systems. Furthermore these observations hold true for the combined dataset of amphibians, reptiles, mammals (which have a conserved XY-system and male-biased ASRs), and birds (which have a conserved ZW system and female-biased ASRs).
It is important to test whether these observations are actually caused by the GSD or whether there are other factors, which could systematically influence ASR:
– ASRs could be influenced by body size and breeding latitude through correlated life history traits like development, growth and reproductive ecology.
– Differences in body size and dispersal between sexes can lead to differences in mortality which influence ASRs.
The authors account for potential effects of sex-biased dispersal, body size, breeding latitude and sexual size dimorphism in a phylogenetically corrected multi-predictor analysis. Although they do find a significant correlation between sexual size dimorphism and ASR as well as between sex-biased dispersal and ASR, the effect of the GSD remains significant in all cases. Because the dataset for sex-biased dispersal is limited to 32 species in total, which is less than 10% of the number of species in the complete dataset, it is not included in the main multi-predictor model.
Another important factor is the effect of phylogenetic relatedness between species: The effects of GSDs on ASRs of more closely related species are more likely to be correlated due to shared genetic and phenotypic traits.
To account for this, phylogenetic corrections, which are based on composite phylogenies of different tetrapod groups, are applied. As these composite phylogenies don’t include branch length information, different methods are used to assign arbitrary branch lengths, which has surprisingly little effect on the results. Two different methods are applied to account for phylogenetic relatedness across samples: Phylogenetic generalized least squares (PGLS) models to test for differences in ASRs between XY and ZW taxa and Pagel’s discreet method (PDM) to test the fit of dependent and independent models of transitions in ASR bias and GSD. As the second model implies, the number of transitions between GSDs should be more important than the phylogenetic relatedness between species. The author’s claim to take this into account by rerunning their analyses while reducing three large groups with a known shared sexual system (mammals, birds and snakes) to a single datapoint, resulting in unchanged significant differences in ASRs between GSDs.
I wonder whether it would also make a difference to reduce further groups, which share non-independent evolution of SDRs, to single datapoints. For example this dataset includes five species of lizards from the family Lacertidae, which are assumed to share a conserved GSD (Rovatsos et al. 2016) and 9 lizard species of the genus Anolis included in the dataset are likely to share a common sex chromosome system (Gamble et al. 2014). Furthermore in many amphibians and reptiles nothing is known about synteny across sex chromosomes and it is likely that a rigorous reduction of GSDs with common ancestry into single datapoints would reduce the number of independent observations and thus statistical power.
However, the number of relevant datapoints in amphibians is fairly limited anyway: Amphibian species with an XY sex determination system show no significant ASR bias (or even a slight male bias after phylogenetic correction). Thus the observed effect within amphibians relies on data for only 11 species with a ZW system.There are good reasons to be careful when making general conclusions from this dataset:
Sex reversal is common in some amphibian species, which could bias the observed ASRs. Furthermore, although the authors claim to have included only species with known GSDs, the GSD for amphibians with homomorphic, microscopically indistinguishable sex chromosomes is difficult to determine and frequent subject of scientific dissent.
One example for this is Bufo viridis. The ASR of B. viridis is strongly male biased (0.70), and the GSD is supposed to be a ZW system based on the entry from www.treeofsex.org. However, the claim that B. viridis is female heterogametic is based on a single study, which detected that all seven females examined in a single Moldavian population were heterozygous for a chromosomal inversion. Such a pattern has never been found in any other green toad population, but instead multiple sex linked genetic markers have been developed, which show male-heterogametic segregation patterns in crosses from different B. viridis populations as well as in the closely related species B. siculus, B. balearicus and B. variabilis (Stöck et al. 2011). In my opinion it would be more appropriate to assign B. viridis to species with XY system, which would result in a decrease in the overall differences in ASRs between both groups.
Possible reasons for the effect of the sex-determination system on adult sex ratios
In general, a skewed adult sex ratio can have two different reasons: a skewed gametic sex ratio or higher mortality of one sex resulting in different sex ratios in adults. In more detail six potential not mutually exclusive explanations of how the GSD could bias adult sex ratios are proposed and discussed:
– Sexual selection in males could increase mortality.
This would be expected to result in a bias towards females in XY and ZW systems and cannot explain male biased ASRs in ZW systems.
– Recessive deleterious mutations on X/Z chromosomes or Y/W specific deleterious mutations.
Recombination suppression on sex chromosomes leads to degeneration of the sex-linked region on Y /W chromosomes, which can result in adverse fitness effects caused by either deleterious mutations on the Y/W, or deleterious recessive mutations on the hemizygous part of the X/Z chromosome.
Based on a population genetic model they develop, the authors claim that the accumulation of deleterious mutations may not be enough to cause the observed adult sex-ratio bias. However, they admit that many of their parameter estimates are very crude and results may vary when other factors are taken into account, like large differences in the rate of deleterious mutations.
The number of deleterious mutations is expected to increase with increasing sex chromosome differentiation and degeneration. Sex chromosome differentiation in tetrapods spans a wide range from completely homomorphic sex chromosomes in many lizards and amphibians but also in some families of snakes and birds to complete loss of the Y chromosome in some mammals. It would thus be interesting to look if there is an association between variable sex chromosome degeneration and skews in the ASR within groups with homologous sex chromosomes.
– Imperfect dosage compensation.
In the heterogametic sex, genes located in the hemizygous region of the X/Z chromosome are present in only one functional copy. In order to reach similar expression levels as in the homogametic sex, the expression of these genes has to be increased. However, research has shown that not all genes are upregulated in the same way and as a result many sex chromosomal genes have a lower expression levels in the heterogametic than in the homogametic sex.
This explanation is unlikely to result in a general pattern across tetrapods, because there are different mechanisms of dosage compensation in vertebrates: mammals deactivate one X chromosome in females to compensate for gene loss on the Y chromosome, while birds show incomplete dosage compensation on a gene-by-gene basis. Since one X is deactivated in the homogametic sex in mammals, we would expect to find sex-specific fitness differences based on dosage compensation only for non-mammals.
– Meiotic drive:
Meiotic drive systems are genetic variants, which favor their own transmission by distorting sex ratios at meiosis. The authors point out, that the observed skews in ASR are unlikely to be caused by meiotic drive, because the sex ratio at birth does not predict the adult sex ratio in mammals and birds. However, there is little information on sex ratio at birth in reptiles or amphibians. Furthermore, a better measure for the effect meiotic drive would be the gametic sex ratio, since the sex ratio may be already skewed at birth due to sex-specific differences in embryonic mortality.
– More rapid degeneration of X and Y chromosomes during lifetime:
The author’s propose, that the Y/W may be more affected by further degeneration during lifetime (for example by increased telomere shortening or loss of epigenetic marks). To my knowledge this is rather speculative, as I am not aware of any results supporting this hypothesis.
– Sexually antagonistic selection:
Loci, which are only beneficial to one sex, but may be detrimental to the other are expected to accumulate on sex chromosomes. In an XY-system, male beneficial loci are expected to be found in linkage disequilibrium with the SDR, which ensures that they are exclusively transmitted to males. The positive fitness effects of these Y/W-linked sexually antagonistic mutations would thus result in a postive skew towards the heterogametic sex (although the evolution of recombination suppression may introduce further degeneration of the Y/W chromosome, which can be detrimental). Furthermore, the authors develop a model for sexually antagonistic selection of loci located on X/Z chromosomes and come to the conclusion, that there are no robust generalizations about the direction of the skew of the adult sex ratio resulting from these loci.
The authors point out, that there is no clear support for any of these hypothesis. Further research could test the assumptions of some of these hypotheses: Recessive deleterious mutations on X/Z chromosomes or Y/W specific deleterious mutations, imperfect dosage compensation and sexually antagonistic selection are all related to sex chromosome degeneration and recombination suppression. Although it is difficult to comparatively quantify sex chromosome degeneration across species, more high quality sequences of sex chromosomes are becoming available and it may soon be possible to link sex chromosome degeneration on a gene level to sex specific fitness differences. A very crude proxy for this would be to include whether sex chromosomes are microscopically distinguishable (heteromorphic) or indistinguishable (homomorphic) in this analysis and test whether this explains significant variance in ASRs. Also further research could clarify whether there is a connection between ASR and sex ratio at birth or even better gametic sex ratio in amphibians or reptiles, which could be indicative of meiotic drive.
Conclusions
Overall, I am skeptical that comparing sexual systems as a simple binary character (male or female heterogametic) does adequately represent the diversity of tetrapod sex chromosome systems and I expect that fitness differences should be more related to sex chromosome degeneration than to the GSD itself. Although a significant proportion of the interspecific variation in ASRs is explained by the GSD in groups with variable sex determination systems, there are multiple possible confounding factors (like sex reversal, problems in determining GSDs, uncertainty of common ancestry of GSDs), which could easily lead to biases in the relatively small number of observations in these groups.
References:
Gamble T, Geneva AJ, Glor RE, Zarkower D (2014). Anolis sex chromosomes are derived from a single ancestral pair. Evolution.68(4):1027-41
Rovatsos M, Jasna V, Altmanova M, Johnson Pokorna M (2016). Conservation of sex chromosomes in lacertid lizards. Molecular Ecology.
Stöck M, Croll D, Dumas Z, Biollay S, Wang J, Perrin N (2011). A cryptic heterogametic transition revealed by sex-linked DNA markers in Palearctic green toads. Journal of Evolutionary Biology. 24:1064-1070