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MARAIS Gabriel

  • LBBE, CNRS / Univ. Lyon 1, Lyon, France
  • Bioinformatics & Computational Biology, Evolutionary Applications, Expression Studies, Genome Evolution, Human Evolution, Molecular Evolution, Population Genetics / Genomics, Reproduction and Sex, Sexual Selection
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Recommendations:  2

Review:  1

Educational and work
see https://lbbe.univ-lyon1.fr/-Marais-Gabriel-.html

Recommendations:  2

29 Jul 2020
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The Y chromosome may contribute to sex-specific ageing in Drosophila

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Y chromosome makes fruit flies die younger

In most animal species, males and females display distinct survival prospect, a phenomenon known as sex gap in longevity (SGL, Marais et al. 2018). The study of SGLs is crucial not only for having a full picture of the causes underlying organisms’ health, aging and death but also to initiate the development of sex-specific anti-aging interventions in humans (Austad and Bartke 2015). Three non-mutually evolutionary causes have been proposed to underlie SGLs (Marais et al. 2018). First, SGLs could be the consequences of sex-differences in life history strategies. For example, evolving dimorphic traits (e.g. body size, ornaments or armaments) may imply unequal physiological costs (e.g. developmental, maintenance) between the sexes and this may result in differences in longevity and aging. Second, mitochondria are usually transmitted by the mother and thus selection is blind to mitochondrial deleterious mutations affecting only males. Such mutations can freely accumulate in the mitochondrial genome and may reduce male longevity, a phenomenon called the mother’s curse (Frank and Hurst 1996). Third, in species with sex chromosomes, all recessive deleterious mutations will be expressed on the single X chromosome in XY males and may reduce their longevity (the unguarded X effect). In addition, the numerous transposable elements (TEs) on the Y chromosome may affect aging. TE activity is normally repressed by epigenetic regulation (DNA methylation, histone modifications and small RNAs). However, it is known that this regulation is disrupted with increasing age. Because of the TE-rich Y chromosome, more TEs may become active in old males than in old females, generating more somatic mutations, accelerating aging and reducing longevity in males (the toxic Y effect, Marais et al. 2018).
The relative contributions of these different effects to SGLs remain unknown. Sex-differences in life history strategies have been considered as the most important cause of SGLs for long (Tidière et al. 2015) but this effect remain equivocal (Lemaître et al. 2020) and cannot explain alone the diversity of patterns observed across species (Marais et al. 2018). Similarly, while studies in Drosophila and humans have shown that the mother’s curse contributes to SGLs in those organisms (e.g. Milot et al. 2007), its contribution may not be strong. Recently, two large-scale comparative analyses have shown that in species with XY chromosomes males show a shorter lifespan compared to females, while in species with ZW chromosomes (a system in which the female are the heterogametic sex and are ZW, and the males ZZ) the opposite pattern is observed (Pipoly et al. 2015; Xirocostas et al. 2020). Apart from these correlational studies, very little experimental tests of the effect of sex chromosomes on longevity have been conducted. In Drosophila, the evidence suggests that the unguarded X effect does not contribute to SGLs (Brengdahl et al. 2018). Whether a toxic Y effect exists in this species was unknown.
In a very elegant study, Brown et al. (2020) provided strong evidence for such a toxic Y effect in Drosophila melanogaster. First, they checked that in the D. melanogaster strain that they were studying (Canton-S), males were indeed dying younger than females. They also confirmed that in this strain, as in others, the male genomes include more repeats and heterochromatin than the female ones using cytometry. A careful analysis of the heterochromatin (using H3K9me2, a repressive histone modification typical of heterochromatin, as a proxy) in old flies revealed that heterochromatin loss was much more important in males than in females, in particular on the Y chromosome (but also to a lesser extent at the pericentromric regions of the autosomes). This change in heterochromatin had two outputs, they found. First, the expression of the genes in those regions was affected. They highlighted that many of such genes are involved in immunity and regulation with a potential impact on longevity. Second, they found a striking TE reactivation. These two effects were stronger in males. While females showed clear reactivation of 6 TEs, with the total fraction of repeats in the transcriptome going from 2% (young females) to 4.6% (old females), males experienced the reactivation of 32 TEs, with the total fraction of repeats in the transcriptome going from 1.6% (young males) to 5.8% (old males). It appeared that most of these TEs are Y-linked. And when focusing on Y-linked repeats, they found that 32 Y-linked TEs became upregulated during male aging and the fraction of Y-linked TEs in the transcriptome increased ninefold.
All these observations clearly suggested that male longevity was decreased because of a toxic Y effect. To really uncover a causal relationship between having a Y chromosome and shorter longevity, Brown et al. (2020) artificially produced flies with atypical karyotypes: X0 males, XXY females and XYY males. This is very interesting as they could uncouple the effect of the phenotypical sex (being male or female) and having a Y chromosome or not, as in fruit flies sex is determined not by the Y chromosome but by the X/autosome ratio. Their results are striking. They found that longevity of the X0 males was the highest (higher than XX females in fact), and that of the XYY males the lowest. Females XXY had intermediate longevities. Importantly, this was found to be robust to genomic background as results were the same using crosses from different strains. When analysing TEs of these flies, they found a particularly strong expression of the Y-linked TEs in old XXY and XYY flies. Interestingly, in young XXY and XYY flies Y-linked TEs expression was also strong, suggesting the chromatin regulation of the Y chromosome is disrupted in these flies.
This work points to the idea that SGLs in D. melanogaster are mainly explained by the toxic Y effect. The molecular details however remain to be elucidated. The effect of the Y chromosome on aging might be more complex than envisioned in the toxic Y model presented above. Brown et al. (2020) indeed found that heterochromatin loss was globally faster in males, both at the Y chromosome and the autosomes. The organisation of the nucleus, in particular of the nucleolus, which is involved in heterochromatin maintenance, involves the sex chromosomes in D. melanogaster as discussed in the paper, and may explain this observation. The epigenetic status of the Y chromosome is known to affect that of all the autosomes in Drosophila (Lemos et al. 2008). Also, in Brown et al. (2020) most of the work (in particular the genomic part) has been done on Canton-S. Only D. melanogaster was studied but limited data suggest different Drosophila species may have different SGLs. The TE analysis is known to be tricky, different tools to analyse TE expression exist (e.g. Lerat et al. 2017; Lanciano and Cristofari 2020). Future work should focus on testing the toxic Y effect on other D. melanogaster strains and other Drosophila species, using different tools to study TE expression, and on dissecting the molecular details of the toxic Y effect.

References

Austad, S. N., and Bartke, A. (2015). Sex differences in longevity and in responses to anti-aging interventions: A Mini-Review. Gerontology, 62(1), 40–46. 10.1159/000381472
Brengdahl, M., Kimber, C. M., Maguire-Baxter, J., and Friberg, U. (2018). Sex differences in life span: Females homozygous for the X chromosome do not suffer the shorter life span predicted by the unguarded X hypothesis. Evolution; international journal of organic evolution, 72(3), 568–577. 10.1111/evo.13434
Brown, E. J., Nguyen, A. H., and Bachtrog, D. (2020). The Y chromosome may contribute to sex-specific ageing in Drosophila. Nature ecology and evolution, 4(6), 853–862. 10.1038/s41559-020-1179-5 or preprint link on bioRxiv
Frank, S. A., and Hurst, L. D. (1996). Mitochondria and male disease. Nature, 383(6597), 224. 10.1038/383224a0
Lanciano, S., and Cristofari, G. (2020). Measuring and interpreting transposable element expression. Nature reviews. Genetics, 10.1038/s41576-020-0251-y. Advance online publication. 10.1038/s41576-020-0251-y
Lemaître, J. F., Ronget, V., Tidière, M., Allainé, D., Berger, V., Cohas, A., Colchero, F., Conde, D. A., Garratt, M., Liker, A., Marais, G., Scheuerlein, A., Székely, T., and Gaillard, J. M. (2020). Sex differences in adult lifespan and aging rates of mortality across wild mammals. Proceedings of the National Academy of Sciences of the United States of America, 117(15), 8546–8553. 10.1073/pnas.1911999117
Lemos, B., Araripe, L. O., and Hartl, D. L. (2008). Polymorphic Y chromosomes harbor cryptic variation with manifold functional consequences. Science (New York, N.Y.), 319(5859), 91–93. 10.1126/science.1148861
Lerat, E., Fablet, M., Modolo, L., Lopez-Maestre, H., and Vieira, C. (2017). TEtools facilitates big data expression analysis of transposable elements and reveals an antagonism between their activity and that of piRNA genes. Nucleic acids research, 45(4), e17. 10.1093/nar/gkw953
Marais, G., Gaillard, J. M., Vieira, C., Plotton, I., Sanlaville, D., Gueyffier, F., and Lemaitre, J. F. (2018). Sex gap in aging and longevity: can sex chromosomes play a role?. Biology of sex differences, 9(1), 33. 10.1186/s13293-018-0181-y
Milot, E., Moreau, C., Gagnon, A., Cohen, A. A., Brais, B., and Labuda, D. (2017). Mother's curse neutralizes natural selection against a human genetic disease over three centuries. Nature ecology and evolution, 1(9), 1400–1406. 10.1038/s41559-017-0276-6
Pipoly, I., Bókony, V., Kirkpatrick, M., Donald, P. F., Székely, T., and Liker, A. (2015). The genetic sex-determination system predicts adult sex ratios in tetrapods. Nature, 527(7576), 91–94. 10.1038/nature15380
Tidière, M., Gaillard, J. M., Müller, D. W., Lackey, L. B., Gimenez, O., Clauss, M., and Lemaître, J. F. (2015). Does sexual selection shape sex differences in longevity and senescence patterns across vertebrates? A review and new insights from captive ruminants. Evolution; international journal of organic evolution, 69(12), 3123–3140. 10.1111/evo.12801
Xirocostas, Z. A., Everingham, S. E., and Moles, A. T. (2020). The sex with the reduced sex chromosome dies earlier: a comparison across the tree of life. Biology letters, 16(3), 20190867. 10.1098/rsbl.2019.0867

24 Jan 2017
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Birth of a W sex chromosome by horizontal transfer of Wolbachia bacterial symbiont genome

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A newly evolved W(olbachia) sex chromosome in pillbug!

In some taxa such as fish and arthropods, closely related species can have different mechanisms of sex determination and in particular different sex chromosomes, which implies that new sex chromosomes are constantly evolving [1]. Several models have been developed to explain this pattern but empirical data are lacking and the causes of the fast sex chromosome turn over remain mysterious [2-4]. Leclerq et al. [5] in a paper that just came out in PNAS have focused on one possible explanation: Wolbachia. This widespread intracellular symbiont of arthropods can manipulate its host reproduction in a number of ways, often by biasing the allocation of resources toward females, the transmitting sex. Perhaps the most spectacular example is seen in pillbugs, where Wolbachia commonly turns infected males into females, thus doubling its effective transmission to grandchildren. Extensive investigations on this phenomenon were initiated 30 years ago in the host species Armadillidium vulgare. The recent paper by Leclerq et al. beautifully validates an hypothesis formulated in these pioneer studies [6], namely, that a nuclear insertion of the Wolbachia genome caused the emergence of new female determining chromosome, that is, a new sex chromosome.

Many populations of A. vulgare are infected by the feminising Wolbachia strain wVulC, where the spread of the bacterium has also induced the loss of the ancestral female determining W chromosome (because feminized ZZ individuals produce females without transmitting any W). In these populations, all individuals carry two Z chromosomes, so that the bacterium is effectively the new sex-determining factor: specimens that received Wolbachia from their mother become females, while the occasional loss of Wolbachia from mothers to eggs allows the production of males. Intriguingly, studies from natural populations also report that some females are devoid both of Wolbachia and the ancestral W chromosome, suggesting the existence of new female determining nuclear factor, the hypothetical “f element”.

Leclerq et al. [5] found the f element and decrypted its origin. By sequencing the genome of a strain carrying the putative f element, they found that a nearly complete wVulC genome got inserted in the nuclear genome and that the chromosome carrying the insertion has effectively become a new W chromosome. The insertion is indeed found only in females, PCRs and pedigree analysis tell. Although the Wolbachia-derived gene(s) that became sex-determining gene(s) remain to be identified among many possible candidates, the genomic and genetic evidence are clear that this Wolbachia insertion is determining sex in this pillbug strain. Leclerq et al. [5] also found that although this insertion is quite recent, many structural changes (rearrangements, duplications) have occurred compared to the wVulC genome, which study will probably help understand which bacterial gene(s) have retained a function in the nucleus of the pillbug. Also, in the future, it will be interesting to understand how and why exactly the nuclear inserted Wolbachia rose in frequency in the pillbug population and how the cytoplasmic Wolbachia was lost, and to tease apart the roles of selection and drift in this event. We highly recommend this paper, which provides clear evidence that Wolbachia has caused sex chromosome turn over in one species, opening the conjecture that it might have done so in many others.

References

[1] Bachtrog D, Mank JE, Peichel CL, Kirkpatrick M, Otto SP, Ashman TL, Hahn MW, Kitano J, Mayrose I, Ming R, Perrin N, Ross L, Valenzuela N, Vamosi JC. 2014. Tree of Sex Consortium. Sex determination: why so many ways of doing it? PLoS Biology 12: e1001899. doi: 10.1371/journal.pbio.1001899

[2] van Doorn GS, Kirkpatrick M. 2007. Turnover of sex chromosomes induced by sexual conflict. Nature 449: 909-912. doi: 10.1038/nature06178

[3] Cordaux R, Bouchon D, Grève P. 2011. The impact of endosymbionts on the evolution of host sex-determination mechanisms. Trends in Genetics 27: 332-341. doi: 10.1016/j.tig.2011.05.002

[4] Blaser O, Neuenschwander S, Perrin N. 2014. Sex-chromosome turnovers: the hot-potato model. American Naturalist 183: 140-146. doi: 10.1086/674026

[5] Leclercq S, Thézé J, Chebbi MA, Giraud I, Moumen B, Ernenwein L, Grève P, Gilbert C, Cordaux R. 2016. Birth of a W sex chromosome by horizontal transfer of Wolbachia bacterial symbiont genome. Proceeding of the National Academy of Science USA 113: 15036-15041. doi: 10.1073/pnas.1608979113

[6] Legrand JJ, Juchault P. 1984. Nouvelles données sur le déterminisme génétique et épigénétique de la monogénie chez le crustacé isopode terrestre Armadillidium vulgare Latr. Génétique Sélection Evolution 16: 57–84. doi: 10.1186/1297-9686-16-1-57

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11 Jun 2019
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A bird’s white-eye view on neosex chromosome evolution

Recommended by based on reviews by Gabriel Marais, Melissa Wilson and 1 anonymous reviewer

Young sex chromosomes discovered in white-eye birds

Recent advances in next-generation sequencing are allowing us to uncover the evolution of sex chromosomes in non-model organisms. This study [1] represents an example of this application to birds of two Sylvioidea species from the genus Zosterops (commonly known as white-eyes). The study is exemplary in the amount and types of data generated and in the thoroughness of the analysis applied. Both male and female genomes were sequenced to allow the authors to identify sex-chromosome specific scaffolds. These data were augmented by generating the transcriptome (RNA-seq) data set. The findings after the analysis of these extensive data are intriguing: neoZ and neoW chromosome scaffolds and their breakpoints were identified. Novel sex chromosome formation appears to be accompanied by translocation events. The timing of formation of novel sex chromosomes was identified using molecular dating and appears to be relatively recent. Yet first signatures of distinct evolutionary patterns of sex chromosomes vs. autosomes could be already identified. These include the accumulation of transposable elements and changes in GC content. The changes in GC content could be explained by biased gene conversion and altered recombination landscape of the neo sex chromosomes. The authors also study divergence and diversity of genes located on the neo sex chromosomes. Here their findings appear to be surprising and need further exploration. The neoW chromosome already shows unique patterns of divergence and diversity at protein-coding genes as compared with genes on either neoZ or autosomes. In contrast, the genes on the neoZ chromosome do not display divergence or diversity patterns different from those for autosomes. This last observation is puzzling and I believe should be explored in further studies. Overall, this study significantly advances our knowledge of the early stages of sex chromosome evolution in vertebrates, provides an example of how such a study could be conducted in other non-model organisms, and provides several avenues for future work.

References

[1] Leroy T., Anselmetti A., Tilak M.K., Bérard S., Csukonyi L., Gabrielli M., Scornavacca C., Milá B., Thébaud C. and Nabholz B. (2019). A bird’s white-eye view on neo-sex chromosome evolution. bioRxiv, 505610, ver. 4 peer-reviewed and recommended by PCI Evolutionary Biology. doi: 10.1101/505610

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MARAIS Gabriel

  • LBBE, CNRS / Univ. Lyon 1, Lyon, France
  • Bioinformatics & Computational Biology, Evolutionary Applications, Expression Studies, Genome Evolution, Human Evolution, Molecular Evolution, Population Genetics / Genomics, Reproduction and Sex, Sexual Selection
  • recommender

Recommendations:  2

Review:  1

Educational and work
see https://lbbe.univ-lyon1.fr/-Marais-Gabriel-.html