MOLECULAR BASIS FOR EVOLUTION OF FOREGUT FERMENTATION

拟议研究的长期目标是了解 哺乳动物适应性进化的分子基础。的研究。 进化机制是高等生物需要周密计划的 比较法。这里计划的比较方法是研究 适应一种生物多样性的分子进化机制 两个远亲群体的前肠发酵消化方式 哺乳动物、反刍动物偶蹄目动物(如牛、羊、鹿)和树叶- 吃眼镜猴(例如，叶猴、根瘤猴)。网络技术的演变 前肠发酵是最近在猴子身上发生的；因此， 与这种适应性转变相关的分子事件可以被检测到 通过正确的序列比较。研究主要集中在两个方面 胃溶菌酶和胰腺核糖核酸酶 被招募为反刍动物和柯北克动物的消化酶 猴子。胃溶菌酶的作用是打开前肠 细菌，以便胰腺可以接触到它们的内容物 宿主的核糖核酸酶和其他消化酶。胃溶菌酶 来自反刍动物和共生动物似乎已经适应了它们的新角色 通过蛋白质序列和功能的趋同。目前还不知道是否 在胰腺的进化过程中也出现了类似的机制 这些哺乳动物的核糖核酸酶，因为没有足够的灵长类序列 以恰当的进化论分析而闻名。为了填补这一空白，一系列 科罗宾和其他灵长类核糖核酸酶和溶菌酶基因将 通过聚合酶链式反应直接测定。这个 这些酶在灵长类动物中的调节进化将通过 蛋白质电泳法和DNA测序法研究调控基因 地区。这些研究将有助于阐明分子机制。 溶菌酶和核糖核酸酶基因表达的变化 灵长类动物，包括人类。在人类中，这两种酶是 各种癌症，包括一些胃癌和胰腺癌。 因此，了解其组织特异性的分子基础 表达可能有助于更好地理解基因调控。 癌细胞。

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.