Ontogeny and Phylogeny of the MHC

MHC 的个体发育和系统发育

基本信息

批准号：
7921769
负责人：
Martin F Flajnik
金额：
$ 7.73万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-22 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7921769
关键词：
Alleles Amphibia Animals Back Base Sequence Binding Biochemistry Biological Metamorphosis Birds Cells Characteristics Chondrichthyes Chordata Communities Data Development Diploidy Elasmobranchii Elements Event Evolution Failure Gene Proteins Gene Silencing Gene Structure Gene Transfer Techniques Genes Genetic Genome Genomics Growth Homeobox Genes Human Immune system Immunocompetent Immunoglobulins Immunologist Individual Insecta Invertebrates Jaw Laboratories Libraries Life Link Locus Control Region Major Histocompatibility Complex Major Histocompatibility Complex Gene Maps Modeling Mus Nurses Osteichthyes Pathway interactions Peptide Transport Peptides Phylogenetic Analysis Phylogeny Polyploidy Process Production Property Proteins Publishing Rana Recombinants Research Personnel Series Shark Skates Skating Specificity Structure Study models Synteny System T-Cell Receptor T-Lymphocyte TAP1 gene TAP2 gene Tadpoles Taxon Tetraodontidae Time Transgenic Organisms Trees Uncertainty Vertebrates Work Xenopus Zebrafish base career comparative driving force fascinate genome sequencing genome-wide in vivo interest mouse genome multicatalytic endopeptidase complex novel peptide I programs research study teleost fish vertebrate genome

项目摘要

DESCRIPTION (provided by applicant): In the past several years, there have been several entire vertebrate genomes sequenced, specifically those of human, mouse, and bony fish (e.g. the pufferfish). In the vertebrate tree, the cartilaginous fish (elasmobranchs including the sharks, skates, and rays) and amphibians are at important phylogenetic junctures, but these animals have not been well studied at the genetic level. Cartilaginous fish are at the base of the jawed vertebrate tree and are the oldest vertebrates to have an adaptive immune system based on the presence of immunoglobulins, T cell receptors, and the major histocompatibility complex (MHC). Amphibians, the first land vertebrates, have been one of the favored non-mammalian models for the study of the adaptive immune system (especially the frog Xenopus, a well known model for developmental biologists). Our analyses of nurse shark and Xenopus MHCs have shown that unlike the bony fish, but like humans, class I, class II, and class III genes are all present in their MHC; thus, representative animals from these vertebrate classes seemingly more accurately represent the hypothetical ancestral vertebrate MHC than the better studied bony fish (e.g. zebrafish). However, unlike humans, there are deep lineages of genes involved in the production (immunoproteasome), transport (TAP1/2), and display (classical class I proteins) of peptides in the MHC class I pathway, at least in Xenopus and probably also in shark. These genes are tightly linked in a true 'class I region,' which likely reflects the situation in the primordial MHC. In Xenopus as well, there is a series of polyploid individuals ranging from 2n-12n, which no doubt arose by genome-wide duplication events (allopolyploidization); the genes of the adaptive immune system become diploidized in the polyploids, presumably to maintain an optimal number of expressed MHC molecules. In order to study the evolution of MHC genetics and the apparent functional consequences of gene organization on the immune system our specific aims are: 1) To compile comparative maps of the MHC in representatives of all vertebrate classes, with an emphasis on nurse shark (cartilaginous fish or elasmobranch) and Xenopus (amphibian); 2) Examine the significance of Xenopus ancient biallelic class I region lineages, specifically by studying the specificity of immunoproteasome subunits, class I peptide-binding, TAP 1/2biochemistry and peptide transport, and in transgenic frogs; and 3) Study gene silencing in polyploid Xenopus: with the advent of genomic sequencing projects in Xenopus (especially the true diploid X. tropicalis), we will begin to analyze the modes of silencing in the tetraploids and eventually the higher order octo- and dodecaploid individuals.

描述（由申请人提供）：在过去的几年中，已经对几种完整的脊椎动物基因组进行了测序，特别是人类、小鼠和硬骨鱼（例如河豚）的基因组。在脊椎动物树中，软骨鱼（软骨鱼类，包括鲨鱼、鳐鱼和鳐鱼）和两栖动物处于重要的系统发育关口，但这些动物尚未在基因水平上得到充分研究。软骨鱼位于有颌脊椎动物树的底部，是最古老的脊椎动物，具有基于免疫球蛋白、T 细胞受体和主要组织相容性复合物 (MHC) 的适应性免疫系统。两栖动物是最早的陆地脊椎动物，一直是适应性免疫系统研究中最受欢迎的非哺乳动物模型之一（尤其是青蛙爪蟾，这是发育生物学家众所周知的模型）。我们对护士鲨和爪蟾 MHC 的分析表明，与硬骨鱼不同，但与人类一样，I 类、II 类和 III 类基因都存在于它们的 MHC 中；因此，这些脊椎动物类的代表性动物似乎比经过更好研究的硬骨鱼（例如斑马鱼）更准确地代表了假设的祖先脊椎动物 MHC。然而，与人类不同的是，MHC I 类途径中涉及肽的产生（免疫蛋白酶体）、运输（TAP1/2）和展示（经典 I 类蛋白）的基因具有深层谱系，至少在非洲爪蟾中是这样，也可能是这样。在鲨鱼中。这些基因在真正的“I 类区域”中紧密相连，这可能反映了原始 MHC 的情况。在非洲爪蟾中，也存在一系列从 2n-12n 不等的多倍体个体，它们无疑是由全基因组复制事件（异源多倍化）引起的；适应性免疫系统的基因在多倍体中变成二倍体，大概是为了维持表达的 MHC 分子的最佳数量。为了研究 MHC 遗传学的进化以及基因组织对免疫系统的明显功能影响，我们的具体目标是： 1) 编制所有脊椎动物类代表的 MHC 比较图，重点是护士鲨（软骨类）鱼或软骨鱼）和爪蟾（两栖动物）； 2) 检查非洲爪蟾古代双等位基因 I 类区域谱系的重要性，特别是通过研究免疫蛋白酶体亚基、I 类肽结合、TAP 1/2 生物化学和肽转运的特异性，以及在转基因青蛙中的重要性； 3）研究多倍体非洲爪蟾的基因沉默：随着非洲爪蟾（尤其是真正的二倍体热带非洲爪蟾）基因组测序项目的出现，我们将开始分析四倍体的沉默模式，并最终分析更高阶的八倍体和十二倍体个人。

项目成果

期刊论文数量（50）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Isolation and characterization of a cDNA encoding a Xenopus 70-kDa heat shock cognate protein, Hsc70.I.

DOI：
10.1016/0305-0491(95)02081-0
发表时间：
1996-04
期刊：
Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology
影响因子：
0
作者：
Adnan Ali;Luisa Salter-Cid;M. Flajnik;John J. Heikkila
通讯作者：
Adnan Ali;Luisa Salter-Cid;M. Flajnik;John J. Heikkila

Isolation of Xenopus LMP-7 homologues. Striking allelic diversity and linkage to MHC.

爪蟾 LMP-7 同源物的分离。

DOI：
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
0
作者：
Namikawa,C;Salter-Cid,L;Flajnik,MF;Kato,Y;Nonaka,M;Sasaki,M
通讯作者：
Sasaki,M

Molecular cloning of a cDNA encoding a Xenopus laevis 70-kDa heat shock cognate protein, hsc70.II.

DOI：
10.1016/s0167-4781(96)00156-x
发表时间：
1996-12
期刊：
Biochimica et biophysica acta
影响因子：
0
作者：
A. Ali;L. Salter-Cid;M. Flajnik;J. Heikkila
通讯作者：
A. Ali;L. Salter-Cid;M. Flajnik;J. Heikkila

Two ancient allelic lineages at the single classical class I locus in the Xenopus MHC.

DOI：
10.4049/jimmunol.163.7.3826
发表时间：
1999-10
期刊：
Journal of immunology
影响因子：
4.4
作者：
M. Flajnik;Y. Ohta;A. Greenberg;L. Salter-Cid;A. Carrizosa;L. Du Pasquier;M. Kasahara
通讯作者：
M. Flajnik;Y. Ohta;A. Greenberg;L. Salter-Cid;A. Carrizosa;L. Du Pasquier;M. Kasahara

Remarkable conservation of distinct nonclassical MHC class I lineages in divergent amphibian species.