FETAL GLOBIN GENES EVOLUTION OF ONTOGENETIC PROGRAMS

该项目有两个密切相关的目标（1）寻求一个更好的 了解灵长类动物的进化关系， 分析珠蛋白基因的结构和表达， 胚胎和胎儿发育;（2）遵循有关 控制基因元件，决定基因何时开启， 通过观察基因表达时间的差异， 在这些密切相关的动物中表达。 重点研究 珠蛋白基因，因为它们经历了一个很好的特征序列， 在人类妊娠期间的开关，和控制（逆转） 这些开关可能在血液学方面具有显著的医疗益处， 镰状细胞性贫血和地中海贫血等疾病。 表达 简介在两个分支的猿猴灵长类动物，catarrhines（旧 世界猴，类人猿）和阔鼻类（新世界猴）， 这表明，在进化过程中， 过渡 我们（1）定位胎儿特异性序列， 人类（基因;（2）使用称为差异化的策略 系统发育足迹，以确定特定的碱基变化， 负责三种不同的模式（表达所见 在非灵长类动物中;和（3）记录体内表达 现存的阔鼻和卡他鼻灵长类的基因模式。 这项工作对阐明这些机制具有重要意义 控制新的基因表达模式， 了解调节血红蛋白转换的因素。 使用 来自华盛顿大学灵长类中心的样本， 发现珠蛋白基因在M.内梅斯特里纳和 在人类中（1）表达是胎儿的;（2）（1）表达到很高的水平， （3）基因间距离为11 kb。 资助NIH赠款HL 33940和RR 00166以及NSF资助INT-9602913。 古德曼，M.，波特，CA，Czelusniak，J.，Page，S.L.，Schneider，H.， Shoshani，J.，Gunnell，G.，和格罗夫斯，C. P. 基于DNA证据的灵长类动物分类， 化石证据 摩尔系统发生网 & Evol. 9：585-598，1998. Goodman，M.人类进化根源的基因组记录。 Am. J. Hum. Genetics 64：31-39，1999.

This project has two closely related aims (1) to seek a better understanding of the evolutionary relationship of the primates through analysis of the structure and expression of the globin genes during embryonic and fetal development; and (2) to follow clues about the controlling gene elements that determine when genes are turned on and off during gestation by observing differences in the timing of gene expression in these closely related animals. The research focuses on the globin genes, since they undergo a well-characterized sequence of switches during gestation in humans, and the control (reversal) of these switches may have significant medical benefits in hematological diseases such as sickle cell anemias and thalassemia. Expression profiles in the two branches of simian primates, catarrhines (Old World Monkeys, hominoids) and platyrrhines (New World Monkeys), suggests that more than one step was involved in the evolutionary transition. We are (1) localizing fe tal-speci fic sequences within the human ( gene; (2) using the strategy called differential phylogenetic footprinting to identify specific base changes that may be responsible for the three different patterns of ( expression seen in nonanthropoid primates; and (3) documenting the in vivo expression patterns of ( genes in extant platyrrhine and catarrhine primates. This work has important implications for clarifying the mechanisms that control new patterns of gene expression as well as for the understanding of factors that regulate hemoglobin switching. Using samples from the University of Washington Primate Center, we have found that globin gene expression is very similar in M. nemestrina and in humans (1) the expression is fetal; (2) (1 is expressed to a much higher level than (2; and (3) the intergenic distance is 11 kb. FUNDING NIH grants HL33940 and RR00166 and NSF grant INT-9602913. Goodman, M., Porter, C.A., Czelusniak, J., Page, S.L., Schneider, H., Shoshani, J., Gunnell, G., and Groves, C.P. Toward a phylogenetic classification of primates based on DNA evidence complemented by fossil evidence. Mol. Phylogenet. & Evol. 9:585-598, 1998. Goodman, M. The Genomic Record of Humankind's Evolutionary Roots. Am. J. Hum. Genetics 64:31-39, 1999.