Studying genetic antagonisms as drivers of genome evolution
Evolutionary stasis of the pseudoautosomal boundary in strepsirrhine primates
Recommendation: posted 22 September 2020, validated 22 September 2020
Sex chromosomes are special in the genome because they are often highly differentiated over much of their lengths and marked by degenerative evolution of their gene content. Understanding why sex chromosomes differentiate requires deciphering the forces driving their recombination patterns. Suppression of recombination may be subject to selection, notably because of functional effects of locking together variation at different traits, as well as longer-term consequences of the inefficient purge of deleterious mutations, both of which may contribute to patterns of differentiation . As an example, male and female functions may reveal intrinsic antagonisms over the optimal genotypes at certain genes or certain combinations of interacting genes. As a result, selection may favour the recruitment of rearrangements blocking recombination and maintaining the association of sex-antagonistic allele combinations with the sex-determining locus.
The hypothesis that sexually antagonistic selection might drive recombination suppression along the sex chromosomes is not new, but there are surprisingly few studies examining this empirically . Support mainly comes from the study of guppy populations Poecilia reticulata in which the level of sexual dimorphism (notably due to male ornaments, subject to sexual selection) varies among populations, and was found to correlate with the length of the non-recombining region on the sex chromosome . But the link is not always that clear. For instance in the fungus Microbotryum violaceum, the mating type loci is characterized by adjacent segments with recombination suppression, despite the near absence of functional differentiation between mating types .
In this study, Shearn and colleagues  explore the patterns of recombination suppression on the sex chromosomes of primates. X and Y chromosomes are strongly differentiated, except in a small region where they recombine with each other, the pseudoautosomal region (PAR). In the clade of apes and monkeys, including humans, large rearrangements have extended the non recombining region stepwise, eroding the PAR. Could this be driven by sexually antagonistic selection in a clade showing strong sexual differentiation?
To evaluate this idea, Shearn et al. have compared the structure of recombination in apes and monkeys to their sister clade with lower levels of sexual dimorphism, the lemurs and the lorises. If sexual antagonism was important in shaping recombination suppression, and assuming lower measures of sexual dimorphism reflect lower sexual antagonism , then lemurs and lorises would be predicted to show a shorter non-recombining region than apes and monkeys.
Lemurs and lorises were terra incognita in terms of genomic research on the sex chromosomes, so Shearn et al. have sequenced the genomes of males and females of different species. To assess whether sequences came from a recombining or non-recombining segment, they used coverage information in males vs females to identify sequences on the X whose copy on the Y is absent or too divergent to map, indicating long-term differentiation (absence of recombination). This approach reveals that the two lineages have undergone different recombination dynamics since they split from their common ancestor: regions which have undergone further structural rearrangements extending the non-recombining region in apes and monkeys, have continued to recombine normally in lemurs and lorises. Consistent with the prediction, macroevolutionary variation in the differentiation of males and females is indeed accompanied by variation in the size of the non-recombining region on the sex chromosome.
Sex chromosomes are excellent examples of how genomes are shaped by selection. By directly exploring recombination patterns on the sex chromosome across all extant primate groups, this study comes as a nice addition to the short series of empirical studies evaluating whether sexual antagonism may drive certain aspects of genome structure. The sexual selection causing sometimes spectacular morphological or behavioural differences between sexes in many animals may be the visible tip of the iceberg of all the antagonisms that characterise male vs. female functions generally . Further research should bring insight into how different flavours or intensities of antagonistic selection can contribute to shape genome variation.
 Charlesworth D (2017) Evolution of recombination rates between sex chromosomes. Philosophical Transactions of the Royal Society B: Biological Sciences, 372, 20160456. https://doi.org/10.1098/rstb.2016.0456
 Wright AE, Darolti I, Bloch NI, Oostra V, Sandkam B, Buechel SD, Kolm N, Breden F, Vicoso B, Mank JE (2017) Convergent recombination suppression suggests role of sexual selection in guppy sex chromosome formation. Nature Communications, 8, 14251. https://doi.org/10.1038/ncomms14251
 Branco S, Badouin H, Vega RCR de la, Gouzy J, Carpentier F, Aguileta G, Siguenza S, Brandenburg J-T, Coelho MA, Hood ME, Giraud T (2017) Evolutionary strata on young mating-type chromosomes despite the lack of sexual antagonism. Proceedings of the National Academy of Sciences, 114, 7067–7072. https://doi.org/10.1073/pnas.1701658114
 Shearn R, Wright AE, Mousset S, Régis C, Penel S, Lemaitre J-F, Douay G, Crouau-Roy B, Lecompte E, Marais GAB (2020) Evolutionary stasis of the pseudoautosomal boundary in strepsirrhine primates. bioRxiv, 445072. https://doi.org/10.1101/445072
 Connallon T, Clark AG (2014) Evolutionary inevitability of sexual antagonism. Proceedings of the Royal Society B: Biological Sciences, 281, 20132123. https://doi.org/10.1098/rspb.2013.2123
Mathieu Joron (2020) Studying genetic antagonisms as drivers of genome evolution. Peer Community in Evolutionary Biology, 100108. 10.24072/pci.evolbiol.100108
The recommender in charge of the evaluation of the article and the reviewers declared that they have no conflict of interest (as defined in the code of conduct of PCI) with the authors or with the content of the article. The authors declared that they comply with the PCI rule of having no financial conflicts of interest in relation to the content of the article.
Evaluation round #3
DOI or URL of the preprint: https://doi.org/10.1101/445072
Version of the preprint: 5
Author's Reply, 07 Sep 2020
Decision by Mathieu Joron, posted 03 Sep 2020
Dear Gabriel Marais
Thanks for submitting the revision of your manuscript “Evolutionary stasis of the pseudoautosomal boundary in strepsirrhine primates”. Looking at your changes and your rebuttal letter, I am of course still willing to recommend your manuscript.
However, now that I see the (formerly missing) table S2 and its content, I find it odd that this section is separated from the main study, and with non-tabular material such as methods description and references only appearing in cells of an excel file. Reading your manuscript again, it appears that the phenotypic analysis stands as an integral part of the logic linking sexual antagonism to your comparative genomics data. So I consider that table S2 should probably be moved to the main manuscript (as a new “Table 1” for instance), rather than appearing as a supplementary.
Making this change seems pretty painless : the text appearing in S2 can be transferred at the end of the main methods section and the literature cited combined within the main list of references. By doing so, the data table, which is of small size, becomes the only tabular material in the document and can easily be pasted in the main PDF. Furthermore, this would not remove the emphasis on the genomic patterns, nor would it require any change in manuscript structure or distract the reader in any way, since the methods are appended after the discussion and with clear subheading. It would improve coherence and long-term accessibility of the data to the reader, which cannot be guaranteed if the phenotypic analysis is separated from the main text.
Apart from this I am satisfied with you changes and I really like you manuscript. I hope you will agree to those slight changes, and am looking forward to the final version.
Evaluation round #2
DOI or URL of the preprint: 10.1101/445072
Version of the preprint: 4
Author's Reply, 27 Aug 2020
Decision by Mathieu Joron, posted 19 Aug 2020
Dear Gabriel Marais
Your revised manuscript was reviewed by three referees, whose comments are pasted below. All referee consider that your manuscript addresses an interesting question and provides a plausible interpretation with solid data and analysis. I agree with them that the manuscript is much improved and that you responded adequately to the earlier comments. Overall I would be glad to recommend your manuscript but two referees and myself still have a number of suggestions and requests for clarifications which seem important to address before formal acceptance.
1- The analysis of sexual dimorphism as a proxy for sexual antagonism is done adequately. However, the methods are totally absent from the manuscript and the supplementary table S2 is also absent (an excel file apparently). Since the methods are explained in the rebuttal letter, I only became aware of this when reading the actual reviews. Of course table S2 and the corresponding methods section are needed in the revised version.
2- Both referees 2 and 3 still point to your interpretation (differences in sexually-antagonistic selection explaining differences in recombination suppression) being speculative, even though the ideas are carefully expressed and you acknowledge other processes. In my view, the logic could be more carefully explained. Indeed, looking for differences in sexual selection as a support for a role of SA selection leads the reader to understand that the differences in SA selection could be sufficient to explain the genomic signals, yet this is unclear and merits a careful explanation. SA selection is multifaceted and sexes in mammals differ in a large number of traits, a fraction of which is directly affected by sexual selection (as measured with morphological markers), so clades with little sexual selection might still undergo significant SA selection throughout the development of males vs females. Perhaps the assumptions associated with using sexual selection as a proxy for SA selection should be briefly explained in order to make the underlying logic clearer, and perhaps the conclusions easier to appreciate.
3- Reviewer 3 has listed a number of additional points, mainly about clarity and logic, and those should be addressed in your revision.
I think the above suggestions should be easy to address by relatively light changes to the text. I am looking forward to reading your final version.
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Reviewed by Qi Zhou, 22 Jul 2020
Reviewed by anonymous reviewer 3, 02 Jul 2020
Reviewed by anonymous reviewer 2, 02 Jul 2020
Evaluation round #1
DOI or URL of the preprint: 10.1101/445072
Version of the preprint: 3
Author's Reply, 28 May 2020
Decision by Mathieu Joron, posted 01 Apr 2019
Dear Rylan Shearn and Gabriel Marais
Your manuscript was reviewed by two referees whose comments are attached. Both referees found your study very interesting, remarking that it contributes nicely to sex chromosome research and should be of broad interest to evolutionary biologists. The role of selection in recombination suppression is a timely subject and this study brings new and interesting data using sex chromosome strata formation, and contrasting the known structure of sex chromosomes in haplorrhine primates to their understudied sister group, the Strepsirrhines.
However, based on those reviews and my own reading, I think that your manuscript requires a few improvements to lead to a recommendation. Both reviewers find the link between the lack of strata 4 and 5 in Strepsirrhines and the lower level of sexually antagonistic selection acting in this group still tenuous, and would have expected a quantitative evaluation of sexual dimorphism, or a discussion of alternative mechanisms. After all, the two groups may vary in many ways which could affect strata formation. Therefore, it seems essential to improve the argument for or against isolating SA selection as the factor causing differences in chromosome structure. Referee 1 would like more details on the use of male/female SNP density of 0.5 to identify regions with suppressed recombination, and the paper would benefit from a critical discussion of the factors affecting this metric and determining the expected values under recombination suppression. Finally, following Referee 2, providing further details on how the PAB and the segments corresponding to strata 4 and 5 in Humans vary among Strepsirrhines would also improve the manuscript.
I would therefore invite you to submit a revised version taking those suggestions into account, and explaining in details how you have dealt with the points raised by the reviewers.
Thank you for sending this interesting work to PCI Evol Biol. I look forward to seeing the revision.