Collaborative Research: Human Origins and the Molecular Genetic Basis of Craniofacial Evolution

包括人类在内的灵长类动物的头部都有相同的基本部分，但每个头部都是不同的。头面部的变化对饮食、防御、姿势、平衡、听力、视力和不断扩大的灵长类大脑的调节都有重要的影响。头骨是一种复杂的适应性结构，自然会出现与组装和协调其形状的遗传机制有关的问题。该项目将确定在活着的猴子和猿类、它们的化石祖先、800只现存的狒狒的谱系以及实验室小鼠之间，头部形状是否会沿着类似的解剖轴线发生变化。计算机断层扫描(CT)将从这些头部获得，并用于测量三维变化。负责这种变异的基因将使用从狒狒和老鼠那里获得的数据来识别。哺乳动物的发育途径是相同的，因此小鼠为灵长类动物的发现提供了重要的比较和实验基础。通过将比较DNA序列和生物信息学分析相结合，并通过在老鼠身上设计类似于狒狒的改变，来研究头部形状的基因结构变化的方式。毫无疑问，许多基因对头部这样的结构有贡献，现代进化和发育遗传学普遍面临的一个普遍挑战是，了解在数百万年的历史和不同的进化分支中，一些基因是否反复参与复杂特征的相似变化，或者共同发育路径中的不同基因是否在每个实例中起作用。该项目将产生大量数据，并将其与分析方法和分析的信息一起发布在可公开访问的网站上。私人投资机构在培训妇女和少数民族学生方面有很好的记录，他们将在从本科生到博士后的各级继续这一传统。人类进化论研究具有强大的公众吸引力，这个项目将特别受到公众媒体的欢迎。

The heads of primates, including humans, all have the same basic parts, yet every head is different. Craniofacial variation has important implications for diet, defense, posture, balance, hearing, vision, and the accommodation of the expanding primate brain. The skull is a complex adaptive structure, and the question naturally arises pertaining to the genetic mechanisms that assemble and coordinate its shape. This project will determine whether variation in head shape occurs along similar anatomical axes among living monkeys and apes, their fossil ancestors, a pedigree of 800 extant baboons, and in laboratory mice. Computerized tomography (CT) scans will be acquired from these heads and used to measure variation in three dimensions. The genes responsible for this variation will be identified using data from baboon and mouse. Developmental pathways are shared among mammals, so mice provide an important comparative and experimental basis for primate findings. The manner by which genes structure variation in head shape will be investigated by combined comparative DNA sequence and bioinformatic analysis, and by engineering similar changes in mice to those seen in baboons. Many genes doubtlessly contribute to structures like the head, and a general challenge to modern evolutionary and developmental genetics generally is to understand whether some genes are repeatedly involved in similar changes in complex traits over the millions of years and different branches of evolution, or whether different genes in the shared developmental pathways are responsible in each instance.The project will generate a large amount of data which will be posted on a publicly accessible website along with information on analytical approaches and analyses. The PIs have a strong record of training women and minority students and they will continue this tradition at all levels from undergraduate to postdoctoral. Human evolutionary studies have a strong public appeal and this project will be exceptionally popular to the public media.