MOLECULAR PHYLOGENY OF OLD WORLD MONKEY HOST SPECIES

旧大陆的猴子和猿是许多能引起人类疾病的传染性病原体（病毒和微生物）的天然宿主。这些病原体包括HIV/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。要了解这些病原体的起源和传播模式，首先需要了解宿主物种的生殖发育。近年来，通过分析整个线粒体DNA（mtDNA）基因组和几个由核DNA（nDNA）编码的非连锁基因座，巨猿和人类的分子同源性终于得到了解决，具有统计学上的信心。根据这一成功的策略，在这里，我们建议生产和分析的DNA序列数据，必要的推断一个强大的分子遗传学的主要血统的旧世界猴。旧大陆猴分为两个亚科，colobines（亚洲叶猴和叶猴，非洲疣猴;约9属30多个物种）和cercopithecines（猕猴，狒狒，白眉猴，长尾猴和绿色猴;约10属50多个物种）。我们计划通过以下方式解决这些属的遗传问题，这些属是导致人类疾病的许多因子的携带者：具体目标1：我们将对9种猕猴的mtDNA全基因组进行纯化、克隆和测序（patas，talapoin，swamp monkey，a guenon，绿色monkey，mandrill，a macaque，and two mangabeys），9 colobines（非洲橄榄猴、红猴和灰猴疣猴，亚洲哈奴曼叶猴、黑叶猴和杜氏叶猴，以及一种叶猴、金丝猴和长鼻猴），以及两种新世界猴（松鼠猴和吼猴）作为额外的外群。具体目的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，每个物种总共约15至20个碱基。具体目标3：将对这些mtDNA和nDNA序列进行遗传学和统计学分析，以检验有关猴子遗传学的关键假设，并产生和检验新的假设。总之，这些遗传数据应该产生一个强大的同源性，显示两个分支的顺序和时间的分歧的主要谱系的OWM。这一系统发生学将提供适当的进化框架，用于推断生物过程，如传染源的起源、宿主和病原体的共同进化、宿主和病原体分子的适应以及物种内和物种间的疾病传播模式。

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.