Natural history and functional divergence of protein tyrosine kinases.

Cellular signaling is important for many biological processes including growth, differentiation, adhesion, motility and apoptosis. The protein tyrosine kinase (PTK) supergene family is the key mediator in cellular signaling in metazoans, directly associated with a variety of human diseases. All PTKs contain a highly conserved catalytic kinase domain, in spite of variable multi-domain structures. Within each PTK gene family, members exhibit functional divergence in substrate-specificity or temporal/tissue-specific expression, although their primary function is conserved. After conducting phylogenetic analysis on major PTK gene families, we found that the expanding of each PTK family was likely caused by gene or genome duplication event(s) that occurred before the emergence of teleosts but after the vertebrate-amphioxus split. We further investigated the evolutionary pattern of functional divergence after gene duplication in those gene families. Our results show that site-specific shifted evolutionary rate (altered functional constraint) is a common pattern in PTK gene family evolution.