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作者 Blekhman, Ran
書名 The evolution of gene regulation in primates
國際標準書號 9781109690187
book jacket
說明 158 p
附註 Source: Dissertation Abstracts International, Volume: 71-04, Section: B, page: 2147
Adviser: Yoav Gilad
Thesis (Ph.D.)--The University of Chicago, 2010
Regulatory changes have long been hypothesized to play an important role in primate evolution. Here, I used custom multi-species microarrays, as well as recently-developed RNA sequencing protocols, to measure gene and exon expression levels in livers, kidneys, and hearts from humans, chimpanzees, and rhesus macaques, in both males and females. Using this comparative expression data, I identified a large number of genes and exons whose inter-species expression profiles are consistent with the action of stabilizing selection on gene regulation, suggesting that gene expression and exon usage is tightly regulated in primates. Among genes whose regulation has likely evolved under directional selection in human, I found an enrichment of genes involved in metabolic pathways, consistent with the hypothesis that shifts in diet underlie many regulatory adaptations in humans. Intriguingly, among genes in which a change in exon usage occurred exclusively in the human lineage, I found an enrichment of genes involved in anatomical structure and morphogenesis, raising the possibility that differences in the regulation of alternative splicing have been an important force in human evolution. I show that a possible mechanism leading to such inter-species variation is species-specific segmental duplications, which are enriched with genes that are differentially expressed between humans and chimpanzees. Considering expression levels in males and females, I identified a subset of genes with conserved sexually dimorphic regulatory patterns across the three species, which I found to be enriched for genes involved in lipid metabolism. Lastly, I found evidence for tissue-specific selection pressures, as well as lower rates of protein evolution for genes whose regulation evolves under natural selection. Put together, these observations of tissue-, species-, and sex-specific evolutionary pressures on gene and exon regulation vii support the notion that adaptive circumscribed changes in gene regulation have fewer deleterious pleiotropic effects compared with changes at the protein sequence level
School code: 0330
Host Item Dissertation Abstracts International 71-04B
主題 Biology, Genetics
Biology, Evolution and Development
Biology, Bioinformatics
Alt Author The University of Chicago. Human Genetics
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