Rodent Serpins : Accelerated Evolution and Novel Specificities
In the basic studies of mammalian physiology, development, pharmacology, anatomy, and other disciplines, rodents (rats and inbred mice) have been assumed to be appropriate model systems in the study of human biology and diseases. In many cases, direct comparisons are valid and valuable. However, recently several disappointing results have been reported using the mouse as a model for studying human diseases. The deletion by homologous recombination of the mouse HPRTase gene has not resulted in Lesch-Nyan Disease1 and the mdx mutation of the dystrophin gene shows few phenotypic similarities to muscular dystrophy.2 In the HPRTase deficiency in mouse, the neurological pathology of Lesch-Nyan is bypassed by a more efficient manner of dealing with toxic metabolites of uric acid.2 These physiological differences are simply due to the fact that the present day rodents and primates shared their last common ancestor some 80 million years ago (Mya). Therefore, different evolutionary pressures have been operating on these species’ ancestors for an appreciable evolutionary time period.
KeywordsNeutral Theory Immunoglobulin Heavy Chain Cosmid Clone Cosmid Library Bovine Pancreatic Trypsin Inhibitor
Unable to display preview. Download preview PDF.
- 3.K.L. Bennett, PA. Lalley, R.K. Barth, and N.D. Hastie, Mapping the structural genes coding for the major urinary proteins in the mouse: combined use of recombinant inbred strains and somatic cell hybrids. Proc. Natl. Acad. Sci. USA 79: 1220 (1982).Google Scholar
- 6.T. Maniatis, E.F. Fritsch, and J. Sambrook, Amplification, storage, and screening of cosmid libraries, in: “Molecular Cloning: A Laboratory Manual” CSH, Cold Spring Harbor, NY p 304 (1982).Google Scholar
- 7.F. Sanger, S. Nicklen, and A.R. Coulson, DNA sequencing with chain terminating inhibitors. Proc. Natl. Acad. Sci. USA 74: 5463 (1977).Google Scholar
- 9.G.D. Kelsey, M. Parkar, and S. Povey, The human alpha-l-anti-trypsin-related sequence gene: isolation and investigation of its expression. Ann. Hum. Genet. 52: 151 (1988).Google Scholar
- 11.M. Rabin, M. Watson, V. Kidd, S.L.C. Woo, W.R. Beeg, and F.H. Ruddle, Regional Localization of a1-antichymotrypsin and Œl-antitrypsin genes on human chromosome 14. Som. Cell Mol. Genet. 12: 209 (1986).Google Scholar
- 12.G.D. Kelsey, D. Abeliovich, C.J. McMahon, D. Whitehouse, G. Corney, S. Povey, DA. Hopkinson, J. Wolfe, G. Mieli Vergani, and A.P. Mowat, Cloning of the human Ct antichymotrypsin gene and genetic analysis of the gene in relation to at antitrypsin deficiency. J. Med. Genet. 25: 361 (1988).Google Scholar
- 14.M.C. Owen, S.O. Brennan, J.H. Lewis, and R.W. Carrell, Mutation of antitrypsin to antithrombin. New Engl. J. Med. 309: 694 (1983).Google Scholar
- 15.A.W. Stephens, B.S. Thalley, and C.H.W. Hirs, Antithrombin III Denver, a reactive site variant. J. Biol. Chem. 262: 1044 (1987).Google Scholar
- 18.M. Kimura, The neutral theory of molecular evolution. Cambridge Univ Press, London (1983).Google Scholar
- 21.W.-H. Li, C.-I. Wu, and C.-C. Luo, A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Molec. Biol. Evol. 2: 150 (1985).Google Scholar