The long-term objective of the proposed research is to understand the molecular basis of adaptive evolution in mammals. The study of evolutionary mechanisms is higher organisms requires a well-planned comparative approach. The comparative approach planned here is to study the molecular evolutionary mechanisms involved in adaptation to a foregut-fermenting mode of digestion in two distantly-related groups of mammals, the ruminant artiodactyls (e.g., cattle, sheep, deer) and leaf- eating colobine monkeys (e.g., langurs, colobus). The evolution of foregut fermentation occurred quite recently in the monkeys; thus, the molecular events associated with this adaptive shift can be detected through proper sequence comparisons. The research focuses on two enzymes, stomach lysozyme and pancreatic ribonuclease, that were recruited to be digestive enzymes in both the ruminants and colobine monkeys. The role of stomach lysozyme is to break open the foregut bacteria so that their contents are accessible to pancreatic ribonuclease and other digestive enzymes of the host. Stomach lysozymes from ruminants and colobines appear to have adopted to their new role through convergence of protein sequence and function. It is not known if similar mechanisms occurred during the evolution of pancreatic ribonuclease in these mammals, because not enough primate sequences are known for proper evolutionary analyses. To fill this gap, sequences of colobine and other primate ribonuclease and lysozyme genes will be determined directly by means of the polymerase chain reaction. The regulatory evolution of these enzymes in the primates will be traced by protein electrophoretic studies and by DNA sequencing of regulatory regions. These studies will help elucidate the molecular mechanisms involved in changes of lysozyme and ribonuclease gene expression in primates, including humans. In humans, these two enzymes are markers for various types of cancer, including some stomach and pancreatic cancers. Thus, understanding the molecular basis for their tissue-specific expression may lead to a better understanding of gene regulation in cancer cells.
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