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.

古人类学利用化石记录来弄清楚人类的定义特征，例如大脑，直立的步行，延长的少年时期和寿命增加，进化。现在，分子生物学的进步使研究可能如何修改我们的野兽基因以产生这些定义特征。该项目的重点是潜在参与早期大脑发育的基因（NR2C1）的演变，并将比较人类基因在小鼠细胞中基因的活性与非人类猿的活性。生成的数据将促进我们对现代人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大的影响，包括潜在的药理应用，新的，共享的遗传数据，非传统，女性研究生的培训以及公共科学教育和外展。核受体基因与对生长和发育，激素调节和行为的控制有关。初步证据表明，这些基因NR2C1之一在人类谱系中经历了阳性选择。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/Bonobos和现代人类的最后一个共同祖先（LCA）。这三个不同的基因变体将插入已敲低NR2C1的小鼠胚胎干细胞中，从而可以定量NR2C1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版本的NR2C1的变化可能导致我们在现代人类大脑中看到的形态或功能变化。关于所有48种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机的数据，将会产生，并将引起公众和生物人类学，进化生物学，医学遗传学，神经科学和药理学的研究人员的关注。这位研究生研究人员多年来一直是生物学老师，致力于为进化过程提供精心设计的学生和公共教育。