As widely used today to infer 'function', the homology search is based on the neutral theory that sites of greatest functional significance are under the strongest selective constraints as well as lowest evolutionary rates, and vice versa. Therefore, site-specific rate changes (or altered selective constraints) are related to functional divergence during protein (family) evolution. In this paper, we review our recent work about this issue. We show a great deal of functional information can be obtained from the evolutionary perspective, which can in turn be used to facilitate high throughput functional assays. The emergence of evolutionary functional genomics is also indicated. The related software DIVERGE can be obtained from http://xgu1.zool.iastate.edu.
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