Tuesday, December 26, 2006

ASPM and flagella   posted by p-ter @ 12/26/2006 04:40:00 PM

In the profile of Bruce Lahn in Science, the following quote, on the possibility that the selective pressure on ASPM could be due to sperm function, stood out to me:
But genome researcher Chris Ponting of the University of Oxford, U.K., notes that microcephalin and ASPM are also expressed outside the brain. In last May's issue of Bioinformatics, he reported that part of ASPM's DNA sequence resembles that of genes involved in the function of flagella, which propel sperm. Earlier work had shown that ASPM is expressed during sperm production. Ponting suggests that natural selection might have acted on flagellar function rather than brain growth.
This would be a striking result, if true. However, I'm skeptical (actually, I'll put the punchline right here: the data provide little, if any, support for this). Let's review:

Ponting's paper is a look at the sequence of the ASPM gene-- it's possible, with this data, to determine the eventual sequence of the protein and see if any regions of the protein ("domains", we call them) are similar to parts of other proteins. If those other proteins have a known function, you might infer that ASPM has a similar function. And indeed, ASPM shares a domain, called ASH, in common with some other proteins. The function of that domain? Well, it's not clear, but as Pontig writes, "[t]hese domains are present in proteins associated with cilia, flagella, the centrosome and the Golgi complex".

This is all well and good, but to jump from a protein possibly "associated with cilia, flagella, the centrosome and the Golgi complex" to saying the selective pressure on the gene is due to flagellar function in sperm is a serious leap indeed. Where does this come from?

Frankly, I have no idea; perhaps I'm missing a key part of the puzzle. But another paper used actual molecular tecniques to look at the distribution of ASPM in neural stem cells. In their words, "Aspm was found to be concentrated at mitotic spindle poles". And what else is found at mitotic spindle poles? Centrosomes, of course, one of the possible locations for ASPM as determined by Pontig. As other centrosomal proteins are known to be involved in brain size, this is perfectly in line with the hypothesis that ASPM is a regulator of brain growth.

I'm not man enough to say the selective pressure on ASPM is definitely not due to a flagellar role in sperm, but for the moment, I ain't buyin' it.