|Budget Amount *help
¥1,500,000 (Direct Cost : ¥1,500,000)
Fiscal Year 1997 : ¥100,000 (Direct Cost : ¥100,000)
Fiscal Year 1996 : ¥200,000 (Direct Cost : ¥200,000)
Fiscal Year 1995 : ¥1,200,000 (Direct Cost : ¥1,200,000)
In the protein kinase family, the basic function of kinase domain is similar among members. In spite of this similarity, a comparison of the evolutionary rates revealed a wide difference among members ; it amounts to about 100 times difference between the maximum and minimum rates. A similar result was also found in members of the immunoglobulin family. In addition, the evolutionary rates of family members that are expressed tissue specifically differ widely, depending on their tissue distribution : members expressed in the brain evolve with significantly slower rates than those expressed in the immune system. These low evolutionary rates of the genes which expressed in the brain (nerve cell) were also found in other gene families, such as nicotinic acetylcholine receptor, rhodopsin, aldolase, cadherin, and so on.
Furthermore, we found extensive tissue specific gene duplications and rapid rates of amino acid substitutions in the early evolution of chordates before the separation of fishes and tetrapods (period I) , while these genetic variations are relatively low in the later period (period II) . Since a variety of tissues and organs evolved rapidly in the former period, it was suggested that there exists a link between evolution at the tissue level and molecular level. To know whether or not Darwinian selection of advatageus mutation is responsible for the rapid rate of amino acid substitutions in the period I, the pattern of amino acid substitutions was analyzed using 11 different gene families. In both periods, the substitution patterns are the conservative type and are very similar to each other. The result suggests that a large fraction of amino acid substitutions observed in the period I is selectively neutral and the rapid rates might be attributed to weak functional constraints. The weak constraints also increase the ratio of advantageous mutations, although minority in number.