Program Nr: 165

Functional non-redundancy and rapid evolution: lessons from a Drosophila cell cycle inhibitor. S.N. Avedisov 1, B.J. Thomas 2, I.B. Rogozin 3, E. Koonin 3. 1) Engelhardt Institute of Molecular Biology, Moscow, Russia; 2) Laboratory of Biochemistry National Cancer Institute, NIH; 3) National Center for Biotechnology Information National Library of Medicine National Institutes of Health.

   The recent sequencing of a complete fruit fly genome has yielded about 30% of predicted genes with no obvious counterparts in other model organisms. This fraction of fast evolving genes remains largely unexplored. Since most Drosophila genes analyzed so far are well conserved among different Drosophila species and have orthologs in other model organisms, the newly released sequencing data prompt to suggest that these "unique" genes are responsible for functions specific for a fly and have no functional homologues in distantly related taxa. Here we present evidence of a striking variability of an essential Drosophila cell cycle regulator, roughex (rux), in closely related fly species. rux has no obvious structural homologs in the data base and therefore can be considered as a Drosophila-specific gene. The unusual level of Rux protein variability indicates that there are very low overall constraints on replacement substitutions, while the functional similarity with vertebrate G1 inhibitors of the Cip/Kip family exemplifies the appearance of certain "species- specific" genes. Our study provides evidence that even the genes involved in key regulatory processes may evolve at very high rate, provided that functionally relevant although small and, therefore, hardly identifiable domains remain intact.