Sex chromosomes in conflict

House mouse (by Wenfei Tong http://darwinsjackal.blogspot.com/)

House mouse (by Wenfei Tong)

Have you thought that not all the genes in your body might have the same evolutionary interests? The mouse Y chromosome has just been revealed after years of superhuman slog and turns out to be strikingly different from other non-recombining sex chromosomes in two main ways. Firstly, the mouse Y contains almost no DNA signatures of its past as a non sex chromosome. Secondly, most of it isn’t “junk”. Both these observations have shown just how much conflict within a genome can shape the evolution of entire chromosomes.

Figure from Sho et a. 2014, showing how much of the mouse Y contains recently evolved, repetitive coding sequences.

Figure from Sho et a. 2014, showing how much of the mouse Y contains recently evolved, repetitive coding sequences.

Just to explain briefly, sex chromosomes have evolved independently lots of times, and are essentially breakaway elements of autosomes that would typically exchange genes every time eggs or sperm are made. When one of these breakaway bits does some gymnastics, such as inverting a chunk of itself, its partner, can no longer pair up and exchange genes with it, so it becomes a non-recombining chromosome like the Y, while its partner (the X in this case), can still recombine if it is in the sex with two of the same sex chromosome.

Why does sex even become linked to these bits of chromosome that do or don’t recombine? My favourite explanation is sexual antagonism. What that means is that because the sexes, by definition, have different reproductive strategies, there will often be genes that increase the fitness of females, but not males, and vice versa. Take, for instance, genes for making a peacock’s tail beautiful and cumbersome. All very good if you’re a male trying to attract mates, but a complete liability if you’re a female just going about your business of rearing children without being eaten. So genes that have such opposing fitness effects in the two sexes would do best by migrating to the sex chromosomes, where they can restrict their effects to one sex.

It sounds like an excellent idea to stick genes for making sperm on a male-specific chromosome, but one of the disadvantages of being stuck on the non-recombining sex chromosome (like the Y), is that without being able to exchange genes with a partner, mistakes in the genetic copying that takes place every time a new sperm is made can’t be easily corrected. As errors accumulate, genes stop working, at which point there is nothing to keep them hanging around and so sex chromosomes without partners tend to get smaller over evolutionary time. The mouse Y has done that to an unprecedented degree, compared to the Y chromosomes of other mammals. Why?

Figure from Sho et al. 2014, showing the percentage of recently acquired, repetitive sequence (i.e. ampliconic in blue) on the mouse Y chromosome compared to other mammalian Ys, and how little ancestral sequence (yellow) is left on the mouse Y.

Figure from Sho et al. 2014, showing the percentage of recently acquired, repetitive sequence (i.e. ampliconic in blue) on the mouse Y chromosome compared to other mammalian Ys, and how little ancestral sequence (yellow) is left on the mouse Y.

This question, and the phenomenon of different chromosomes being present in different numbers in the two sexes brings us back to the mouse Y and its battle with the mouse X. Imagine yourself a gene on the X chromosome. If you can exclude the wretched Y from getting into any sperm, then you would have twice the chance of getting into the next generation. This phenomenon—called meiotic drive or segregation distortion—exists in genes in any part of the genome, but is particularly handy in this case because instead of having to screen for different copies of the gene to see if it’s being passed on unequally to the next generation, you can just look at the sex of the offspring.

That is exactly what a group of mouse biologists had found in mice in 2009. Take away part of the Y chromosome, and that male produces mostly daughters (from X bearing sperm), get rid of a similar sequence on the X chromosome, and he starts producing mostly sons. What appears to be going on here, is that some cunning gene on the X chromosome managed to manipulate the sperm making process to bias transmission of itself on the X chromosome at the expense of the Y chromosomes. This was no good for genes sitting on the Y, but it was lucky enough to acquire a similar gene that allows it to supress the driving copy on the X. The driving X version then retaliated by copying itself, and so the version on the Y had to do the same in defence, and after some impressive escalation, we now see 50-100 copies of each of these genes on both sex chromosomes in the house mouse genus.

Figure from Bachtrog 2014 illustrating how meiotic drive can lead to co-amplification on the mouse sex chromosomes.

Figure from Bachtrog (2014) illustrating how meiotic drive can lead to co-amplification on the mouse sex chromosomes.

That is just one of three vastly repetitive gene families on the mouse Y that is also present on the X, and that actually code for proteins rather than nonsense. So one of the most remarkable findings from a complete sequence of the mouse Y, and which partly explains why it took so long to assemble, is that to a much greater extent than in other mammalian Ys, most of it comprises repeated and recently acquired sequences that do something. And that something appears to be to suppress driving copies of the same gene families on the X chromosome. One of the possible consequences of this massive expansion of competing copies, is that the ancestral genes on the mouse Y have disappeared at a faster rate than in other mammals without intensely conflicting sex chromosomes. Another is that the sex chromosomal arms race might be freer to escalate in some mating systems than others, because of the potential costs of carrying a driving gene when a mouse must make as much sperm as possible to outcompete the sperm of other males.

References

Bachtrog, D. (2014). Signs of Genomic Battles in Mouse Sex Chromosomes. Cell, 159(4), 716–718. doi:10.1016/j.cell.2014.10.036

Bellott, D. W., Hughes, J. F., Skaletsky, H., Brown, L. G., Pyntikova, T., Cho, T.-J., … Page, D. C. (2014). Mammalian y chromosomes retain widely expressed dosage-sensitive regulators. Nature, 508(7497), 494–499. doi:10.1038/nature13206

Cocquet, J., Ellis, P. J. I., Mahadevaiah, S. K., Affara, N. A., Vaiman, D., & Burgoyne, P. S. (2012). A Genetic Basis for a Postmeiotic X Versus Y Chromosome Intragenomic Conflict in the Mouse. PLoS Genet, 8(9), e1002900. doi:10.1371/journal.pgen.1002900

Cocquet, J., Ellis, P. J. I., Yamauchi, Y., Mahadevaiah, S. K., Affara, N. A., Ward, M. A., & Burgoyne, P. S. (2009). The Multicopy Gene Sly Represses the Sex Chromosomes in the Male Mouse Germline after Meiosis. PLoS Biol, 7(11), e1000244. doi:10.1371/journal.pbio.1000244

Hughes, J. F., Skaletsky, H., & Page, D. C. (2012). Sequencing of rhesus macaque Y chromosome clarifies origins and evolution of the DAZ (Deleted in AZoospermia) genes. BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology, 34(12), 1035–1044. doi:10.1002/bies.201200066

Hughes, J. F., Skaletsky, H., Pyntikova, T., Graves, T. A., van Daalen, S. K. M., Minx, P. J., … Page, D. C. (2010). Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content. Nature, 463(7280), 536–539. doi:10.1038/nature08700

Soh, Y. Q. S., Alföldi, J., Pyntikova, T., Brown, L. G., Graves, T., Minx, P. J., … Page, D. C. (2014). Sequencing the Mouse Y Chromosome Reveals Convergent Gene Acquisition and Amplification on Both Sex Chromosomes. Cell, 159(4), 800–813. doi:10.1016/j.cell.2014.09.052

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