FETAL GLOBIN GENES: EVOLUTION OF ONTOGENETIC PROGRAMS

胎儿珠蛋白基因：个体遗传程序的进化

• 批准号: 3346338
• 负责人: MORRIS GOODMAN
• 金额: $ 12.28万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-15 至 1988-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3346338
• 关键词: gene expression; genetic transcription; hemoglobin; human population genetics

A comprehensive understanding of the evolutionary history of Gamma-globin genes and the mammalian Beta-globin gene clusters in which they occur is being sought. A principal goal is to uncover new clues about the ontogenetic program which controls human fetal hemoglobin synthesis. The Gamma-globin genes of humans and other simian primates encode the polypeptide which distinguishes fetal hemoglobin (Alpha 2 Gamma 2) from embryonic (Zeta 2 Epsilon 2; Alpha 2 Epsilon 2) and adult (Alpha 2 Delta 2; Alpha 2 Beta 2) hemoglobins. As rabbits and mice have Gamma genes expressed along with Epsilon genes only during embryonic life, the first primates possibly had embryonic Gamma genes rather than fetal ones. If so, recruitment of Gamma to be a fetal gene occurred in later primates ancestral to the simian primates (i.e. to Anthropoidea). Phylogenetic tests of this hypothesis will provide new data on conserved functionally active DNA sequences within the human Beta-globin gene cluster and on organizational features of the human cluster that may be implicated in the developmental switches from Epsilon to Gamma and then to Delta and Beta gene expression. Detailed characterizations of the Delta-globin gene clusters of lower (prosimian) and higher (simian) primates and extensive DNA sequencing on Gamma and other gene regions, especially between Gamma and Delta loci, will be carried out. This primate inter Gamma - Delta region contains the non-expressed Psi Beta1 locus which shares with the expressed goat embryonic Epsilon II locus a common ancestral gene called Eta to distinguish it from Epsilon, Gamma, Delta and Beta loci. Extending the DNA analyses to such non-primate mammals as opossum, armadillo, tree shrew, and flying lemur will furnish an enlarged data base with which to improve a proposed five loci model 5' - Epsilon - Gamma - Eta - Delta - Beta-3' for the Beta-globin gene clusters of early mammals and proto-primates by allowing more accurate deductions to made on the lengths of intergenic regions and the nature of their sequences. In addition parallel studies of the hhemoglobin chains produced by fetuses of two lower primates, galago and tarsier, will provide pertinent data for testing the embryonic Gamma (proto-primate) to fetal Gamma (proto-Anthropoidea) recruitment hypothesis. The extensive sequence data to be gathered on simian primates should then help reveal evolutionary changes which occurred in overall organization of the proto-Anthropoidea Beta-globin gene cluster and in positioning of specific sequences within the cluster. This data will also characterize the finer organization and recent sequence patterns which evolved in the human Beta--globin gene cluster.

全面了解γ-珠蛋白的进化史 基因和它们所在的哺乳动物β-珠蛋白基因簇是 被追捕。一个主要的目标是发现关于 控制人类胎儿血红蛋白合成的个体发育程序。这个 人类和其他灵长类动物的伽马珠蛋白基因编码 区分胎儿血红蛋白(Alpha 2 Gamma 2)和 胚胎(Zeta 2 Epsilon 2；Alpha 2 Epsilon 2)和成年(Alpha 2 Delta 2)α2β2)血红蛋白。因为兔子和小鼠都有伽马基因 只在胚胎生命中与Epsilon基因一起表达，第一 灵长类动物可能有胚胎伽马基因，而不是胎儿基因。如果是的话， 在后来的灵长类动物中，伽玛基因被招募为胎儿基因 猿猴灵长类的祖先(即人类总科)。系统发育 对这一假说的检验将为保守的功能提供新的数据 人β-珠蛋白基因簇内的活性DNA序列及其他 可能涉及的人类集群的组织特征 发展从Epsilon到Gamma再到Delta和Beta 基因表达。 Low的Delta-珠蛋白基因簇的详细特征 (猿猴)和高等(猿猴)灵长类动物和广泛的DNA测序 Gamma和其他基因区域，特别是Gamma和Delta基因座之间的基因区域，将 被执行。这个灵长类的Gamma-Delta区域包含 与表达的山羊共有的未表达的Psi Beta1基因座 胚胎Epsilon II基因是一种常见的祖先基因，称为Eta to 将其与Epsilon、Gamma、Delta和Beta基因座区分开来。延伸DNA 对负鼠、螳螂、树鼠等非灵长类哺乳动物的分析 飞行狐猴将提供一个更大的数据库，用来改进 提出了5‘-Epsilon-Gamma-Eta-Delta-Beta-3’基因座模型 早期哺乳动物和原始灵长类动物的β-珠蛋白基因簇 允许对基因间的长度做出更准确的推断 区域及其序列的性质。此外，平行研究还包括 两种低等灵长类动物Galago的胎儿产生的血红蛋白链 和Tarsier，将为测试胚胎伽马提供相关数据 (原始灵长类)到胎儿伽玛(原始人类)招募 假设。将收集的关于猿猴灵长类的大量序列数据 应该有助于揭示总体上发生的进化变化 原人类总科贝塔-珠蛋白基因簇的组织和在 该簇内特定序列的定位。该数据还将 描述更精细的组织和最近的序列模式， 在人类贝塔--珠蛋白基因簇中进化。