Doctoral Dissertation Research: Genetic Changes During Human Brain Evolution

人类进化出了相对于身体大小来说非常大的大脑，大脑皮层中神经元的丰富程度令人惊讶。人类学的大量研究都集中在描述在人类进化过程中导致这些变化的适应压力上。然而，人类大脑扩张背后的基因变化尚未得到充分探索。该项目将通过使用实验模型研究人类基因变异对大脑发育的影响，来检验关于人类大脑进化的假设。这项研究对理解人类大脑在细胞和分子水平上的独特之处具有广泛的意义，对神经发育障碍的医学治疗具有转化价值。在这项研究中，追求STEM职业的本科生将在实验室中接受分子生物学和生物信息学技术的指导和培训。研究成果将被用作1)向公众、K-12学生和本科生传播人类进化和遗传学知识的教育工具，以及2)激励年轻、未来的女性科学家参加“女性在数学、工程和科学方面更出色”（FEMMES）项目。本研究采用多学科的方法来研究人类进化史如何塑造了人类大脑扩张的分子和生理机制。在实验室中，将研究人类和非人类灵长类动物的神经细胞，以探索人类的遗传变异如何进化，从而塑造发育中的大脑。该项目结合了基因编辑、RNA测序和免疫组织化学来确定人类特异性基因序列在大脑发育过程中与大脑大小变化相对应的功能作用。这些发现将促进对人类大脑分子进化的理解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Humans evolved very large brains relative to their body size, with a remarkable enrichment of neurons in the cerebral cortex. Extensive efforts in anthropology have focused on delineating the adaptive pressures that led to these changes during human evolution. However, the genetic changes underlying human brain expansion have not been fully explored. This project will test hypotheses about human brain evolution by studying the impact of human genetic variation on brain development using experimental models. This research has broad implications for understanding what makes the human brain unique at the cellular and molecular levels, with translational value for medical treatment of neurodevelopmental disorders. During this research, undergraduate students pursuing careers in STEM will be mentored and trained in molecular biology and bioinformatics techniques in the laboratory. Research findings will be used as 1) an educational tool for spreading knowledge about human evolution and genetics with the general public, K-12 students, and undergraduate students, as well as 2) a motivational platform for the young, future women scientists in the Females Excelling More in Mathematics, Engineering and Science (FEMMES) Program. The proposed research takes a multi-disciplinary approach to investigate how human evolutionary history has shaped the molecular and physiological mechanisms of human brain expansion. In the laboratory, human and non-human primate neural cells will be studied to explore how genetic variation evolved in humans to shape the developing brain. This project uses a combination of gene editing, RNA sequencing, and immunohistochemistry to determine the functional role of human-specific genetic sequence during brain development that corresponds to changes in brain size. These findings will advance the understanding of the molecular evolution of the human brain.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.