Sex and Genomics

Mammals, including humans, have cytologically distinct X and Y sex chromosomes. We could annotate and map sequence for the X along with autosomes, a task made easier by the complete conservation of the X among placental mammals. The degenerate Y presented a challenge because it is full of repetitive sequence and poorly conserved because of differential gene attrition and retroposon insertion. The male-dominant sex determiing gene SRY on the Y was discovered using positional cloning. Birds present the reverse problem; the highly conserved Z chromosome common to both sexes could be sequenced and annotated, but the female-specific W presented a challenge that has only recently been met. The sex determining gene DMRT1on the bird Z chromosome was identified by analogy with other DM-domain bearing gene, and shown to work by differential dosage.

In reptiles and fish, however, there is a huge variety of sex determining mechanisms. Some are genetic, including XY systems (male heterogamety) and ZW systems (female heterogamety), some highly differentiated like the human XY and chicken ZW, and some cytologically homomorphic. However, many reptiles lack sex chromosomes, determining sex via incubation temperature. Some species, like the dragon lizard, do both, having chromosomal sex determination at moderate temperature and a sex-switch override at extremes. These systems may prove to be the most informative, yielding novel sex determining genes or, more remarkably, orthologues of the same genes, and providing insights into how they interact with the environment via epigenetic pathways.