Alu-mediated phylogenetic novelties in gene regulation and development

Alu-mediated phylogenetic novelties in gene regulation and development
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DOI:
10.1006/jmbi.2000.3795
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发表时间:
2000-06-16
影响因子:
5.6
通讯作者:
Dugaiczyk, A
Dugaiczyk, A
中科院分区:
生物学2区
文献类型:
--
作者:
Hamdi, HK;Nishio, H;Dugaiczyk, A

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差异基因表达是生物学的核心,并负责所有发育过程,包括细胞的生长和分化。也许甚至物种形成也可以被定义为在进化过程中差异基因表达的变化。目前的工作是一个系统发育研究的四个Alu元件已知在人类基因调控功能。这四种元件已被证明通过负钙响应元件调节甲状旁腺激素(PTH)基因,通过顺式作用正/负调控元件调节造血细胞特异性Fc γ RT-γ受体基因,通过顺式作用正/负调控元件调节CNS特异性烟碱乙酰胆碱受体α 3基因,以及通过复杂的转录调控因子调节T细胞特异性CD 8 α基因。发现影响差异基因表达的四个Alu元素在七种灵长类动物(人类、黑猩猩、大猩猩、猩猩、狒狒、恒河猴和猕猴)中的分布差异与这些物种公认的亲缘关系一致。这些结果建立了基因调控和灵长类动物分化之间的联系。这种基因调控的进化变异也提出了一种新的实验系统,通过并排研究来自两种灵长类动物的相同基因的调控,来研究基因表达的非常复杂的转录调控,这两种灵长类动物的基因的顺式作用调控元件不同。(C)北京大学出版社.
Differential gene expression lies at the heart of biology and is responsible for all developmental processes, including the growth and differentiation of cells. Perhaps even speciation could be defined as a change in differential gene expression over evolutionary time. The present work is a phylogenetic study of four Alu elements known to have gene regulatory functions in the human. The four elements have been shown to regulate the parathyroid hormone (PTH) gene via a negative calcium-response element, the hematopoietic cell-specific Fc epsilon RT-gamma receptor gene via a cis-acting positive/negative regulatory element, the CNS-specific nicotinic acetylcholine receptor alpha 3 gene via a cis-acting positive/negative control element, and the T-cell-specific CD8 alpha gene via a complex transcriptional regulator. The four Alu elements that impact differential gene expression were found to be differentially distributed among seven primate species (human, chimpanzee, gorilla, orangutan, baboon, rhesus, and macaque) in a way that is congruent with an accepted phylogeny of these species. The results establish a link between gene regulation and the divergence of primates. This evolutionary variation in gene regulation also suggests a novel experimental system to study the very complex transcriptional regulation of gene expression, by studying side-by-side the regulation of the same gene from two primate species that differ in the cis-acting regulatory elements of the gene. (C) 2000 Academic Press.