STRUCTURAL ANALYSIS OF ETS-RELATED GENES IN LOWER EUKARYOTES

低等真核生物中 ETS 相关基因的结构分析

• 批准号: 3774855
• 负责人: J A LAUTENBERGER
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3774855
• 关键词: Saccharomyces cerevisiae; alpharetrovirus; biochemical evolution; chickens; eukaryote; fungal genetics; gene duplication; gene expression; gene mutation; genetic library; genome; molecular cloning; molecular oncology; nucleic acid hybridization; nucleic acid probes; nucleic acid sequence; oncogenes; open reading frames; protein sequence; protooncogene; sea urchins; virus genetics

Studies of ets family genes in lower eukaryotes focused on: 1) possible ets sequences in the baker's yeast (Saccharomyces cerevisiae); 2) an erg homolog in a sea urchin; 3) an inversion found in avian leukemia virus E26 v-ets; 4) a phylogenetic analysis of the entire ets family. (1) Low stringency hybridization of S. cerevisiae DNA digested by four different sets of enzymes to a radiolabeled sea urchin ets probe revealed approximately four major bands for each set of enzymes. Three unique bacteriophage lambda clones that hybridize to ets sequences were isolated by screening a S. cerevisiae genomic library under the same conditions. (2) A genomic clone from the sea urchin Lytechinus variegatus was found to be the homolog of the ets family genes, ERG and Fli-1. It contains an open reading frame, of which the 173 amino acid coding region begins at a splice acceptor site. The first 84 of these amino acids are homologous to all ets family genes, while the remainder of the sequence represents a highly-conserved erg-specific domain. (3) The segment of the E26 genome near the termination of the p135gag-myb-ets open reading frame was found to contain an inversion of the chicken ets-1 sequence. The inversion contains at least 41 bp, and may be as large as 46 bp. This results in the replacement of 13 amino acids of chicken ets-1, with 16 amino acids derived from the reverse complement of the normal ets-1 coding strand or read-through into E26 env sequences. The altered carboxy terminal sequences may be responsible for the different oncogenic potential of v- ets, as contrasted to chicken ets-1. (4) A phylogenetic analysis of 32 ets sequences revealed that this family of genes may be divided into 11 subgroups. Analysis of these clusters allows the history of the evolution of the ets gene family to be examined in the context of metazoan radiation. Homologous ets-related genes have been found in three phyla (Chordata, Echinodermata, and Arthropoda). Of the 10 subgroups, 4 have representatives in more than one phyla, implying that several gene duplications occurred prior to the divergence of these phyla over 500 million years ago.

低等真核生物中 ets 家族基因的研究重点是：1）可能 面包酵母（酿酒酵母）中的 ets 序列； 2) 尔格 海胆的同源物； 3）禽白血病病毒E26中发现的倒置 v-ets； 4）整个ets家族的系统发育分析。 (1) 低 四种不同酶切的酿酒酵母 DNA 的严格杂交 放射性标记海胆 ets 探针的酶组被揭示 每组酶大约有四个主要条带。 三个独特 分离出与 ets 序列杂交的 lambda 噬菌体克隆 通过在相同条件下筛选酿酒酵母基因组文库。 (2) 来自海胆 Lytechinus variegatus 的基因组克隆被发现 是 ets 家族基因 ERG 和 Fli-1 的同源物。 它包含一个 开放阅读框，其中 173 个氨基酸的编码区起始于 剪接受体位点。 这些氨基酸的前 84 个与 所有 ets 家族基因，而序列的其余部分代表 高度保守的 erg 特异性结构域。 (3) E26基因组片段 在 p135gag-myb-ets 开放阅读框的末端附近发现 包含鸡 ets-1 序列的倒置。 反转 至少包含 41 bp，并且可能长达 46 bp。 这导致 将鸡ets-1的13个氨基酸替换为16个氨基酸 衍生自正常 ets-1 编码链的反向互补体或 通读 E26 env 序列。 改变的羧基末端 序列可能是导致 v- 不同致癌潜力的原因 ets，与鸡 ets-1 相比。 (4) 32个的系统发育分析 ets 序列显示该基因家族可分为 11 个 亚组。 对这些簇的分析可以了解进化的历史 在后生动物的背景下检查 ets 基因家族 辐射。 在三个门中发现同源 ets 相关基因 （脊索动物门、棘皮动物门和节肢动物门）。 10 个小组中，有 4 个小组 代表多个门，这意味着多个基因 重复发生在这些门的分化之前 500 多个 万年前。