Friday, March 7, 2008

The descent of Y

One of the most obvious features of our genome, is the large difference between in the X and Y chromosomes. The Y chromosome is small compared to its partner the X, much of its DNA content is made up of repetitive DNA and it codes for few genes.

Much of the degeneration of the Y is thought to due to the lack of recombination on the Y chromosome. Recombination is thought to be initially suppressed between the homologous chromosomes around the sex determining locus, and then extend as sex-specific coadapted complexes of genes linked to the sex determining locus build up (which recombination would destroy). The lack of recombination means that the fate of mutations that occur on the Y chromosome are coupled: A beneficial mutation drags along deleterious mutations that occur on its background as it sweeps to fixation (hitchhiking). Deleterious variation also builds up as in the absence of recombination haplotypes lacking deleterious mutations can not be recreated once they are lost by genetic drift (Mullers rachet).

However, studying the formation of the human Y chromosome is difficult. The event happened millions of years ago, and while we can learn something about the event by looking over different mammalian species we are still very limited in what we can say. A different approach to learn about sex chromosomes is to look not at old sex chromosomes (where much of the action occurred long ago), but to study new sex chromosomes or new additions to sex chromosomes. This is one of the wonderful things about biology, no matter how strange the event, it is often occurring in multiple species independently as we speak. Thus if you want to learn about something that happened in the history of one species, looking for it happening currently in another is a great tactic. As sequencing and other resources become cheaper, this will make this approach in genetics even easier.

Young sex chromosomes have been identified in a number of species ( see here ), these are associated with locally suppressed recombination (around the sex determination locus), causing these regions to start to degenerate (this paper is also a good introduction to the evolutionary dynamics of sex chromosomes).

Another example of the degeneration of the Y chromosome due to lack of recombination, are fusions between autosomes and existing sex chromosomes. These fusions happen relatively often (fusions are a relatively common chromosomal abnormality in humans) and sometimes they survive and are fixed in the population. A number of fusions between sex chromosomes and autosomes are known in Drosophila. These vary in age, and so provide a good system for studying this problem. When an autosome becomes fused to the Y chromosome (a neo-Y) it ceased to recombine, as it is transmitted through males (which have no recombination in Drosophila ). The neo-X, which is the homolog of the neo-Y continues to experience recombination. A recent paper studies the decay of the neo-Y of Drosophia Miranda, this fusion is believed to have formed about a million years ago. The authors sequenced ~2.5Mb of neo-sex chromosome. They find that half the genes on the neo-Y are psuedogenized, due to the build up of deleterious mutations. While there counterparts on the neo-X are much more conserved. The Y chromosome is also rapidly accumulating transposable elements, around 20% of the neo-Y is transposable elements comapred to ~1% on the neo-X. Thus the degeneration of the neo-Y is incredibly rapid. This suggests that the homologous genes on the X chromosome will also have to evolve rapidly to cope with the loss of their partner. For example, if the neo-Y copy of the gene is non-functional, the copy on the neo-X will have to be up-regulated to compensate for this loss. Thus dosage compensation will have to evolve quickly on the neo-X. It will be really great to learn more about the evolution of sex chromosomes from these young sex chromosome systems, as more of them get sequenced.


Genomic degradation of a young Y chromosome in Drosophila miranda.
Bachtrog D, Hom E, Wong KM, Maside X, de Jong P. Genome Biology 2008

Steps in the evolution of heteromorphic sex chromosomes.
Charlesworth D, Charlesworth B, Marais G. Heredity. 2005


RPM said...

Not all Y chromosomes harbor sex determining loci. In humans, the Y has the male determining gene, but the same is not true in Drosophila. Additionally, there's no need to worry about evolving suppressed recombination between X and Y chromosomes in Drosophila b/c there is no male recombination in nearly all Drosophila species. And some Drosophila Y chromosomes are quite large (although they're gene poor).

Drosophila sex chromosomes are really different than eutherian sex chromosomes.

G said...

I agree that the absence of recombination in Drosophila males is a large difference from the situation in eutherian mammals. But Drosophila fusions do offer a somewhat unique chance to learn about the consequences of no recombination, in a system with good genetic resources.

Species with an achiasmatic sex are rare, making Drosophila somewhat exceptional. It is more usual to find a difference in recombination between the sexes rather than an absence. In species where one sex is achiasmatic, it is always the heterogametic sex where recombination is absent (the 'Haldane-Huxley' rule). This suggests that the reduced recombination is necessary or causal in the formation of the degenerate sex chromosome in these species. See for example Lenormand, Genetics 2003.