FETAL GLOBIN GENES: EVOLUTION OF ONTOGENETIC PROGRAMS

对γ-珠蛋白进化历史的全面认识 基因和它们所处的哺乳动物β-珠蛋白基因簇是 被寻找。 一个主要的目标是发现新的线索， 控制人类胎儿血红蛋白合成的个体发育程序。 的 人类和其他猿类灵长类的γ-珠蛋白基因编码 一种区分胎儿血红蛋白（α 2 γ 2）和 胚胎（Zeta 2 Epidemi 2; Alpha 2 Epidemi 2）和成体（Alpha 2 Delta 2; α 2 β 2）血红蛋白。 因为兔子和老鼠都有伽马基因 只在胚胎期与Epoxy基因一起沿着表达， 灵长类动物可能有胚胎伽马基因而不是胎儿基因。 如果是这样的话， 在后来的灵长类动物中，γ基因被募集为胎儿基因 猿类灵长类的祖先（即人类总科）。 系统发育 这一假设的测试将提供新的数据保守的功能 人β-珠蛋白基因簇内的活性DNA序列和 人类集群的组织特征，可能涉及在 从Epaly到Gamma再到Delta和Beta的发展转换 基因表达。 详细描述了低分子量的δ-珠蛋白基因簇， （原猿）和更高（猿）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， 执行。 这个灵长类的γ-δ区域包含了 与表达的山羊共享的未表达的Psi β 1基因座 胚胎Epoxy II基因座是一个共同的祖先基因，称为Eta， 将其与Epsilon、Gamma、Delta和Beta基因座区分开来。 延伸DNA 对负鼠、犰狳、树鼩等非灵长类哺乳动物的分析， 飞行狐猴将提供一个扩大的数据库，以改善 提出了5个基因座模型5' -Ep 3-Gamma-Eta-Delta-Beta-3'， 早期哺乳动物和原始灵长类的β-珠蛋白基因簇， 从而可以更准确地推断基因间的长度， 区域及其序列的性质。 此外，平行研究 两种低等灵长类动物的胎儿产生的血红蛋白链， 和眼镜猴，将提供相关的数据，测试胚胎伽马 （原灵长类）至胎儿伽马（原人类总科）招募 假说. 在猿类灵长类动物身上收集的大量序列数据 应该有助于揭示整体上发生在 原人类β-珠蛋白基因簇的组织， 特定序列在簇内的定位。 这些数据也将 描述了更精细的组织和最近的序列模式， 在人类β-珠蛋白基因簇中进化。

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.