At its core human evolutionary biology seeks to answer the question of how the defining characteristics of modern humans evolved, such as large-brains, obligatory bipedal gait, extended juvenile period, and increased longevity. Traditional fossil-based research uses morphology to infer behavior and life history and only recently have researchers been able to make predictions regarding the effect of modifications to the DNA and proteins of our forbearers. Using these innovative methods we investigated the molecular evolution of a superfamily of transcription factors called the Nuclear Receptors. The patterns of sequence evolution observed in our bioinformatic analyses suggest a shift in the intensity of selection pressure occurred on NR2C1, a gene that plays a role early in embryonic stem cell proliferation and neuronal differentiation. Methods are now available to reconstruct ancestral DNA and its corresponding protein sequences and thus generate testable hypotheses about the functional evolution of genes on specific lineages. These methods allowed us to analyze how modifications to the modern human version of NR2C1 affected the ability of an embryonic stem cell to remain in its proliferative state. We began by creating three different copies of our gene of interest: the human copy, the chimpanzee copy, and the ancestral copy of NR2C1 for the inferred last common ancestor of chimpanzee and modern humans. Inserting these three different gene variants into mouse embryonic stem cells that have had NR2C1 knocked down allowed us to quantitatively analyze the transcriptional and regulatory functions of NR2C1.
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|Advisor:||Wood, Bernard A.|
|Commitee:||Bradley, Brenda J., Maynard, Thomas, Sherwood, Chester C., Wildman, Derek|
|School:||The George Washington University|
|School Location:||United States -- District of Columbia|
|Source:||DAI-B 76/08(E), Dissertation Abstracts International|
|Subjects:||Evolution and Development|
|Keywords:||Ancestral gene reconstruction, Codon models, Nr2c1, Nuclear receptors, Olfactory epithelium, Testicular receptor|
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