Doctoral Dissertation Research: Genetics of hominin brain evolution

博士论文研究：人类大脑进化的遗传学

• 批准号: 1455625
• 负责人: Bernard Wood
• 金额: $ 1.68万
• 依托单位: George Washington University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1455625&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Genetics; hominin

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.

古人类学使用化石记录来研究人类的定义特征是如何以及何时进化的，例如大大脑，直立行走，延长的青少年时期和增加的寿命。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定义特征的。该项目的重点是可能参与早期大脑发育的基因（NR 2C 1）的进化，并将在小鼠细胞中比较人类与非人类猿类基因的活性。所产生的数据将促进我们对现代人类大脑进化和发展中独特分子相互作用的理解。此外，该项目还对社会产生了更广泛的影响，包括潜在的药理学应用、产生新的共享遗传数据、培训非传统的女研究生以及公共科学教育和宣传。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NR 2C 1在人类谱系中经历了正选择。在这项为期六个月的研究中，将为现代人类和黑猩猩生成NR 2C 1的拷贝，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到NR 2C 1敲低的小鼠胚胎干细胞中，从而可以定量NR 2C 1的转录和调节功能。这些方法将使研究人员能够分析现代人类NR 2C 1的改变如何导致我们在现代人类大脑中看到的形态或功能变化。所有48个灵长类动物核受体基因的灵长类动物氨基酸取代的位置和时间的数据将被生成，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有关进化过程的精心设计的教育。