Molecular and Functional Characterization of an Ancient Histocompatibility System

古代组织相容性系统的分子和功能表征

• 批准号: 0315968
• 负责人: Luis Cadavid
• 金额: $ 50.88万
• 依托单位: University of New Mexico
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0315968&HistoricalAwards=false
• 关键词: Molecular; Functional; Characterization; Ancient; Histocompatibility

Sessile, colonial invertebrates often encounter members of their own species as they grow on hard surfaces. The nature and outcomes of such encounters are mediated by highly discriminatory recognition systems. In general, close relatives fuse whereas unrelated colonies reject. These histocompatibility phenomena have been unambiguously observed in all major colonial invertebrate groups, and have attracted the attention of various biological disciplines. In particular, they are often claimed to reflect the evolutionary origins of the vertebrate immune system, and have played a prominent role in evolutionary theory and ecology as a paradigm of competitive interactions within species. Despite the prevalence of histocompatibility and their putative biological importance, the responsible genes and molecules have not been identified in any colonial invertebrate.Histocompatibility in the colonial hydroid Hydractinia symbiolongicarpus (Cnidaria; Hydrozoa) is better understood than in perhaps any other colonial invertebrate. The response results from a dose-dependent interaction of at least two gene loci encoded in a single chromosomal interval. This project aims to identify and functionally characterize the histocompatibility genes in Hydractinia. Specifically, genetic markers located at close proximity to the target genes will be used to identify the relevant genomic segment from a Hydractinia DNA library. Plausible candidate histocompatibility genes will be identified by sequencing the entire segment. Candidate genes will be subsequently knocked-out in vivo to test their role in histocompatibility responses. Characterization of the invertebrate histocompatibility molecules will prove instrumental for understanding, at its most basic level, the nature of competitive interactions amongst conspecifics. Furthermore, it will settle the long-standing debate on the evolutionary relationship between vertebrate immunity and invertebrate histocompatibility. The project will integrate research and education by developing new curricula, providing research opportunities for undergraduates, and recruiting and training underrepresented groups in science.

固着的群居无脊椎动物在坚硬的表面上生长时，经常会遇到自己物种的成员。这种接触的性质和结果是由高度歧视性的承认制度调停的。一般来说，近亲融合，而不相关的殖民地拒绝。这些组织亲和性现象在所有主要的殖民地无脊椎动物群体中都被明确地观察到，并引起了各个生物学学科的注意。特别是，它们经常被认为反映了脊椎动物免疫系统的进化起源，并作为物种内竞争相互作用的范例在进化理论和生态学中发挥了突出的作用。尽管组织亲和性及其推测的生物学重要性普遍存在，但尚未在任何集群无脊椎动物中鉴定出负责的基因和分子。这种反应是由在单个染色体间隔中编码的至少两个基因座之间的剂量依赖性相互作用造成的。本项目旨在鉴定和鉴定水生孢子菌的组织相容性基因。具体地说，位于目标基因附近的遗传标记将被用于从Hydractinia DNA文库中识别相关的基因组片段。看似合理的候选组织相容性基因将通过对整个片段进行测序来识别。候选基因随后将在体内被敲除，以测试它们在组织相容性反应中的作用。无脊椎动物组织相容性分子的特征将被证明有助于在最基本的水平上理解同种生物之间竞争相互作用的性质。此外，它还将解决长期以来关于脊椎动物免疫和无脊椎动物组织相容性之间进化关系的争论。该项目将通过开发新的课程，为本科生提供研究机会，以及招募和培训科学方面代表性不足的群体，将研究和教育结合起来。