Functional divergence and genome evolution of vertebrate protein kinases (kinome)

The emerging complete and nearly complete genome sequences have provided a significant amount of materials for large-scale comparative genomic analysis. Novel methods have been developed to elucidate the function of gene products and functional interacting networks. Many of these post-genomic attempts have focused on unveiling the evolutionary forces that have shaped the network organization. Among various evolutionary forces, duplication of functional domain, individual gene, chromosomal segment, or entire genome has long been thought as primary resource for the function novelties in a vast number of gene families. It is therefore intriguing to quantitatively trace the changes of evolutionary constraints after a duplication event.;This study is focused on the exploitation of the functional divergence and evolutionary patterns in vertebrate kinase complements (denoted as kinomes) and kinase-regulated signaling transduction pathways, using a combinatorial statistical and evolutionary approach. The analysis of an individual kinase gene family (Jak), protein tyrosine kinase superfamily, and a kinase mediated signaling transduction pathway (TGF-beta) showed that functional divergence (altered functional constraint) after (domain or gene) duplication is a general pattern. Moreover, the age distribution of the vertebrate kinomes showed that (1) The major kinase-related animal specific signal-transduction pathways have been generated through an ancient continuous domain shuffling (or duplications) during the time period from early stage of eukaryotes to metazoan evolution; (2) Vertebrate tissue-specificity of signal-transduction is facilitated by large-scale duplication event(s) in the early stage of vertebrates; and (3) The kinase pseudogenes are generated through either segmental duplication or retrotransposition very recently