MOLECULAR PHYLOGENY OF OLD WORLD MONKEY HOST SPECIES

东半球的猴子和类人猿是许多可导致人类疾病的传染病病原体(病毒和微生物)的自然宿主。这些病原体包括艾滋病毒/SIV慢病毒、埃博拉病毒、疱疹病毒和许多其他外源性和内源性病毒。要了解这类病原体的起源和传播模式，首先需要了解宿主物种的系统发展史。近年来，通过分析类人猿和人类的全部线粒体DNA(MtDNA)基因组和由核DNA(NDNA)编码的几个不连锁的基因座，大猩猩和人类的分子系统学终于在统计上得到了解决。根据这一成功的策略，我们建议在这里产生和分析必要的DNA序列数据，以推断东半球猴子主要谱系的统计上可靠的分子系统学。东半球的猴子分为两个亚科，孔雀科(亚洲叶猴和非洲鳞猴；约9属30多种)和颈尾猴(猕猴、狒狒、山冠猴、孔雀和绿猴；约10属50多种)。我们计划通过做以下工作来解决这些属的系统发育问题：特定的目标1：我们将纯化、克隆和测序9种尾猴(帕塔斯、塔拉佩因、沼泽猴、一只刺猴、绿猴、山竹、一只猕猴和两只山竹)、9只短尾猴(非洲橄榄、红毛猴和大头猴，以及亚洲的哈努曼、黑叶猴和黑叶猴，以及一只叶猴、金丝猴和长吻猴)的整个mtDNA基因组，以及另外两个新世界猴子(松鼠和喉咙猴)作为额外的类群。特定目的2：使用与上述相同的物种，我们将对几个未连锁的nDNA基因座进行测序，每个物种的总碱基约为15~20kb。具体目的3：将对这些mtDNA和nDNA序列进行系统发育和统计分析，以检验有关猴子系统发育的关键假说，以及产生和检验新的假说。综上所述，这些遗传数据应该会产生一个强大的系统发育图，显示出OWM主要谱系的分枝顺序和分化时间。这一系统发育将为推断生物过程提供适当的进化框架，如感染源的起源、宿主和病原体的共同进化、宿主和病原体分子的适应以及疾病在物种内和物种之间的传播模式。

The Old World monkeys and apes are natural hosts for many infectious agents (viruses and microbes) that can cause human disease. These include such pathogens as the HIV/SIV lentiviruses, Ebola viruses, herpesviruses, and numerous other exogenous and endogenous viruses. Understanding the origins and transmission patterns of such agents requires first knowing the phylogeny of the host species. Within recent years, the molecular phylogeny of the great apes and humans has finally been resolved, with statistical confidence, by analysis of their entire mitochondrial DNA (mtDNA) genomes and several unlinked loci encoded by nuclear DNA (nDNA). Following this successful strategy, here we propose to produce and analyze the DNA sequence data necessary for inference of a statistically-robust molecular phylogeny of the major lineages of Old World monkeys. The Old World monkeys are divided into two subfamilies, the colobines (Asian langurs and leaf-monkeys, and African colobus monkeys; over 30 species in about 9 genera) and the cercopithecines (macaques, baboons, mangabeys, guenons, and green monkeys; over 50 species in about 10 genera). We plan to resolve the phylogeny of these genera, which are carriers of many agents that cause human disease, by doing the following: SPECIFIC AIM 1: We will purify, clone, and sequence the entire mtDNA genomes from 9 cercopithecines (patas, talapoin, swamp monkey, a guenon, green monkey, mandrill, a macaque, and two mangabeys), 9 colobines (the African olive, red, and guereza colobus monkeys, and the Asian Hanuman, dusky and douc langurs, and a leaf, golden, and proboscis monkey), and two New World monkeys (squirrel and howler monkey) as additional outgroups. SPECIFIC AIM 2: Using the same species as above, we will sequence several unlinked nDNA loci, totaling about 15 to 20 kilobases per species. SPECIFIC AIM 3: These mtDNA and nDNA sequences will be analyzed phylogenetically and statistically to test key hypotheses concerning monkey phylogeny, as well as to generate and test new hypotheses. Taken together, these genetic data should produce a robust phylogeny, showing both the branching order and the times of divergence of the major lineages of OWMs. This phylogeny will provide the proper evolutionary framework for inferences about biological processes such as the origin of infectious agents, the coevolution of hosts and pathogens, adaptation of host and pathogen molecules, and patterns of disease transmission within and between species.