Thursday, March 17, 2005

SeXed up

This week's Nature carries the genomic sequence of the human X chomosome. This chromosome was tricky to sequence because it is full of repetitive DNA sequences, which resemble each other quite closely, so the still 85% complete sequence arrives about 4 years after the publication of the draft sequence of the human genome.(Since sequencing of a whole chromosome involves breaking the chromosome into small pieces, sequenced, and reassembled, repetitive DNA acts like a jigsaw puzzle full of the color blue: every piece starts to look like every other.) Despite the special rules of inheritance for sex chromosomes, the sequence of the X chromosome reveals quite a bit of genetic exchange between the X and Y, which has been progressively shut off during evolution.

The X-chromosome is of very high interest to neuroscientists, because it is the site of a disproportionate number of human mutations resulting in mental retardation . Groups like the European Mental Retardation consortium are hunting through the X chromosome to find the estimated 20 different X-linked genetic defects which result in mental retardation.

Moreover, there are some hints from an identical twin study that the X Chromosome may harbor genes important for verbal skills and social behavior. Girl identical twins (who have two copies of their X chromosome) differ in which X chromosome is active in which cells, whereas boy twins don't "have a choice" and use the same X chromosome in all cells. This study found that boy identical twins had more highly correlated scores in tests of prosocial behavior and verbal ability. Interestingly, girls with Turner syndome (only one X chromosome) where the X came from the Dad have much better verbal skills than girls with Turner syndrome in which the copy came from the mother. Although the proposed mechanism, called imprinting, would have to be confirmed by identification of the causative gene, the Turner syndrome observation again suggests that there's a lot more to X than meets the Y. The X chromosome will be an interesting hunting ground for cognitive abilities we associate with being human.

The Beeb , reading the same Nature stuff, points out that the entire female X-chromosome is not inactivated but rather about 15% of the genes remain active. For these 15%, females are expressing two copies. This region may be a source of differences between the genders.

I can't leave a discussion of sex chromosomes without discussing my avatar, the platypus, which never seems to do anything the easy way. Platypusses have 5 X chromosomes, and males have 5 Ys; and they have to resort to a very strange subcellular chromosome chain during sperm formation to be sure all of the sex chromosomes, Xs and Ys, sort to the right place (which they do, a big percentage of the time). Al though platypusses lack SRY, the gene important for human male differentiation, their X chromosome number 5 actually has a relative of DMTR1, a gene implicated in bird sex determination.

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