Doctoral Dissertation Research: Genetics of hominin brain evolution

古人类学利用化石记录来研究人类的决定性特征，如大脑袋、直立行走、延长的少年期和延长的寿命，是如何以及何时进化的。分子生物学的进步使我们有可能研究我们祖先的基因是如何被修改以产生这些决定性的特征的。这个项目的重点是一个可能参与早期大脑发育的基因（NR2C1）的进化，并将在小鼠细胞中比较人类和非人类猿类基因的活性。生成的数据将促进我们对现代人类大脑进化和发展中独特的分子相互作用的理解。此外，该项目对社会具有更广泛的影响，包括潜在的药理学应用、新的共享遗传数据的产生、非传统女性研究生的培训以及公共科学教育和推广。核受体基因与生长发育、激素调节和行为的控制有关。初步证据表明，其中一个基因NR2C1在人类谱系中经历了积极的选择。在这项为期六个月的研究中，将为现代人类和黑猩猩生成NR2C1的副本，并预测/重建黑猩猩/倭黑猩猩和现代人类的最后共同祖先（LCA）。这三种不同的基因变体将被插入NR2C1基因被敲除的小鼠胚胎干细胞中，从而量化NR2C1基因的转录和调控功能。这些方法将使研究人员能够分析现代人类NR2C1基因的改变是如何导致我们在现代人类大脑中看到的形态或功能变化的。有关所有48个灵长类动物核受体基因的灵长类动物氨基酸替换位置和时间的数据将产生，并将引起公众和生物人类学、进化生物学、医学遗传学、神经科学和药理学研究人员的兴趣。这位研究生研究员拥有多年的生物学教师经验，致力于为学生和公众提供精心设计的关于进化过程的教育。

Paleoanthropology uses the fossil record to work out how and when the defining characteristics of humans, such as large-brains, upright walking, extended juvenile period, and increased longevity, evolved. Advances in molecular biology now make it possible to investigate how the genes of our forbearers might have been modified to generate these defining characteristics. This project focuses on the evolution of a gene (NR2C1) potentially involved in early brain development, and will compare the activity of human versus non-human ape versions of the gene in mouse cells. The data that are generated will advance our understanding of the unique molecular interactions at play in the evolution and development of the modern human brain. In addition, the project has broader impacts to society that include potential pharmacological applications, generation of new, shared genetic data, training of a non-traditional, female graduate student, and public science education and outreach. Nuclear receptor genes are implicated in the control of growth and development, hormone regulation and behavior. Preliminary evidence suggests that one of these genes, NR2C1, has undergone positive selection in the human lineage. In this six-month study, copies of NR2C1 will be generated for modern humans and chimpanzees, and predicted/reconstructed for a last common ancestor (LCA) of chimpanzees/bonobos and modern humans. These three different gene variants will be inserted into mouse embryonic stem cells that have had NR2C1 knocked down, allowing quantification of the transcriptional and regulatory functions of NR2C1. These methods will allow the investigators to analyze how alterations to the modern human version of NR2C1 may have resulted in the morphological or functional changes we see in the modern human brain. Data on the locations and timing of primate amino acid substitutions for all 48 primate nuclear receptor genes will be generated and will be of interest to the general public and to researchers in biological anthropology, evolutionary biology, medical genetics, neuroscience, and pharmacology. The graduate student researcher, who has years of experience as a biology teacher, is dedicated to providing well-designed student and public education about evolutionary processes.