COMPARABLE RATES OF GENE LOSS AND FUNCTIONAL DIVERGENCE AFTER GENOME DUPLICATIONS EARLY IN VERTEBRATE EVOLUTION

Duplicated genes are an important source of new protein functions and novel developmental and physiological pathways. Whereas most models fo r fate of duplicated genes show that they tend to be rapidly lost, mod els for pathway evolution suggest that many duplicated genes rapidly a cquire novel functions. Little empirical evidence is available, howeve r, for the relative rates of gene loss vs. divergence to help resolve these contradictory expectations. Gene families resulting from genome duplications provide an opportunity to address this apparent contradic tion. With genome duplication, the number of duplicated genes in a gen e family is at most 2(n), where n is the number of duplications. The s ize of each gene family, e.g., 1, 2, 3, ..., 2(n), reflects the patter ns of gene loss vs, functional divergence after duplication. We focuse d on gene families in humans and mice that arose from genome duplicati ons in early vertebrate evolution and we analyzed the frequency distri bution of gene family size, i.e., the number of families with two, thr ee or four members. All the models that we evaluated showed that dupli cated genes are almost as likely to acquire a new and essential functi on as to be lost through acquisition of mutations that compromise prot ein function. An explanation for the unexpectedly high rate of functio nal divergence is that duplication allows genes to accumulate more neu tral than disadvantageous mutations, thereby providing more opportunit ies to acquire diversified functions and pathways.