Sunday, March 23, 2008

Mutating males

A short but nice article by Doris Bachtrog, looking at whether there is a faster mutation rate in males compared to females in Drosophila. Studies of a number of vertebrates have shown a faster rate of substitution on the Y compared to the X at putatively neutral sites, thus suggesting a faster male mutation rate (as under neutrality the substitution rate is the mutation rate). This high rate of mutation in males is thought to be due to the larger number of cell divisions in the germ line of males compared females. Previous work has not seen this effect in Drosophila. Bachtrog used a set of orthologous genes on the recently formed neo-sex chromosomes of D. miranda (I discussed some of her work on this system in a previous post). The recent sex linkage of these chromosomes means that the genes on them have altered the proportion of generations they spend in the male and female germ line, making them an excellent system for looking at male and female mutation rates. To look at putatively neutral changes, Bachtrog looks at changes in short introns and at synonymous changes in genes (where the changes are classified by their direction with respect to codon bias). She finds a consistently lower rate of substitution at sites on the neo-X chromosome compared to the neo-Y, suggesting that in D miranda there is a higher rate of mutation in males.

I guess I'm still still slightly concerned that the higher rate of changes on the neo-Y could reflect relaxed constraint, but as the effect is seen across a range of different putatively neutral sites, a higher mutation rate seems the parsimonious conclusion. It would be interesting to know whether this higher male mutation rate is true of the entire Drosophila clade, or if is restricted to certain species due to differences in number of cell divisions. I wonder whether whole genome resequencing (or sequencing of a reduced representation) could be used on mutation accumulation lines to look into this. One issue with this experimental approach would be that generation time in the lab might differ from that in the wild, but it could offer a complementary way to look at this problem.

Bachtrog D. Evidence for male-driven evolution in Drosophila.
Mol Biol Evol. 2008 Apr;25(4):617-9


RPM said...

There is variation in Drosophila species for the number of pre-meiotic divisions in spermatogenesis. The hard part will be finding homologous Y chromosome regions in species with different numbers of pre-meiotic divisions.

G said...

True. This may well be hard to assess phylogenetically, also it is not clear that variation seen between species in the lab reflects variation in nature.

In mutation accumulation lines it would perhaps be enough to show that the mutation rate on the Y > mutation rate on the autosomes > mutation rate on the X. This conclusion could be strengthen by showing in multiple species that the strength of this relationship was predicted by the number of pre-meiotic divisions.

Another thought I had was that it might be possible to make a autosomal chromosome, be transmitted only through the male germ line. If this was done in a mutation accumulation experiment the mutation rate on the autosome transmitted only through the male germ line could be assessed, and compared to the rate on the chromosome when it was transmitted as normal (assessed by normal mutation accumulation line). I think that forcing chromosomes to be passed on through only the male germ line, is something that Bill Rice has used this for assessing sexual conflict in experimental evolution (though I might be wrong).

Obviously if genome sequencing gets cheap enough, it would be possible to do away with the mutation accumulation lines and just sequence a bunch of genomes transmitted from males and females to get the rate directly.