Gene Expression

Let’s talk about sex….

PLOS has a new paper out which fleshes out how SRY might play a critical role in sex determination in mammals. Here is the press release. Below the fold I’ve taken figure 7 from their paper and cropped and reedited it a bit for ease of viewing, as well as adding minor parenthetical remarks (e.g., I assume most readers know the common symbol for repression in molecular genetic models, but some might not). Molecular genetics really isn’t my thing, but it is good to know if we are interested in the phenotypic impact of a particular locus (e.g., SRY) the particular genotypic dynamics that underlay it.1 Also, I’ve reviewd the sex determination literature in mammals recently (which was smaller than I’d expected), and it did surprise me that females were not just the “default” pathways as I’d expected, there is active suppression of the development of the Mullerian ducts in male embryos.

1 – The reason it isn’t my thing is that some molecular genetics people seem to only give a perfunctory nod to evolutionary thought in their fixation on specific processes. That’s fine, but it seems tome that Theodosius Dobzhanksy’s assertion that nothing in biology makes sense except in the light of evolution could be modified to biology is more fun if you add an evolutionary angle to your thinking. See Genes in Conflict. I mean that’s what science is supposed to be about, right? Having fun on the NSF and NIH’s dime :)



  1. #1 CanuckRob
    May 24, 2006

    Great post and links. Thanks. The press release says that SRY is only found in mammals. Is it found in all mammals?

  2. #2 razib
    May 24, 2006

    Is it found in all mammals

    well, a lot of this work has been done in humans & mice, so “all mammals” is a big category. the plos paper makes pretty strong claims for its ubiquity in the introduction, but look at wiki and you’ll see that it claims that SRY isn’t as big a deal as people make it out to be. like i said, i don’t know much about this, but my survey of the lit. recently because of a project made me a little more skeptical about the details in this field.

  3. #3 MIke McKeown
    May 24, 2006

    SRY appears to be lacking in platypus, but they have an extremely complicated Y chromosome situation involving multiple chromosomal translocations. The exact determinant there is not known.

    Marsupials do have an SRY gene that appears to function in a similar sex determination pathway as in placentals.

    Evidence from the Page lab and others comparing the sequence of the Y chromosome of placental mammals with the X, suggests that the lineage to the human Y, and that of other placental mammals began about 300 M years ago, with establishment of SRY as the male determining factor. From then on the Y underwent a series of recombination-suppressing events, usually inversion of sequences within the Y, that isolated it from the previously homologous X chromosome. This isolation resulted in genetic deterioration of many functions on the Y. There has also been a series of transpositions from various autosomes to the Y of genes important for functions such as male fertility.

    Birds use a different primary determining gene(s) and a different version of chromsomal sex determination. Notably females are the heterogametic sex, having a Z chromosome and a W chromosome. Males have two Zs and no W. The exact mechanism by which ZW is female and ZZ is male is not clear. Leading, not mutually exclusive hypotheses, involve the dosage of the DRMT1 gene on the Z, which is similar to genes involved in masculization in mammals and various other species. This would be male positive and present in two doses. The second possiblity is a gene that is W specific and has potential pro-female activity. Such a candidate exists. The kinds of sex determination errors that occur in birds are probably most easily accounted for by a mix of W-linked female favoring factors and Z linked male favoring factors.

    Reptiles are all over the map for mechanisms. Many use temperature or other versions of environmental dependent sex, but there are chromosomal sex determination systems as well, including, presumably, in the those dinosaurs that are the ancestors of modern birds.

    Fish use too many mechanism to keep track of.

    Interestingly, there are commonalities among all of these. In particular, gonadal sex determination is a critical early step, and this is usually triggered in the somatic cells of the gonad, not the germ cells. Genes such as SOX9 (similar but not identical to SRY), DMRT, the Wilms Tumor Gene (WT), the Anti-Mullerian Hormone gene (AMH) and others keep appearing, but with varying contributions to differentiation. Usually the result is gonadal sex establishment leading to sex hormones and thereby sex differentation of the rest of the body. This is simplified but true generally.

    Thus, aspects of vertebrate sex are conserved, but the primary determinant is highly variable and even the relative importance of the conserved players changes from lineage to lineage.

  4. #4 IndianCowboy
    May 24, 2006

    Mike, thanks for that summary. I knew that things differed between various vertebrate taxa but wasn’t sure to what degree.

    Also, may I add that razib hit the nail on the head when he said that ‘biology is more fun if you add an evolutionary angle to your thinking.’ It’s been the primary way I haven’t driven a pencil through my eye during all the med schoo lectures; I keep thinking of the evolution of whatever’s being discussed and why it might’ve turned out like that.