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.
One of the fundamental questions in the field of biology, including the biology of humans, concerns the process of evolution and the origin of new anatomical or morphological traits. While research has provided us with extensive knowledge of evolutionary history and the general mechanisms of evolution, there are few specific examples of morphological traits in humans or nonhuman primates for which we have a detailed understanding of how specific genetic changes produced particular new anatomical characteristics that were favored by natural selection. Evolutionary changes in the size and shape of the skull have been important aspects of primate evolutionary history, and the history of our own species. The goal of this project is to investigate the genetic causes of individual differences in the size and shape of the skull (cranium) within a specific population of baboons (genus Papio). The research team for this project included Dr. J. Cheverud (Washington University), Drs. K. Weiss and J. Rightsmeier (Penn State Univ.) and Dr. J. Rogers (Baylor College of Medicine). Baboons are among the most extensively studied of nonhuman primates, having received attention from researchers interested in behavior, anatomy, physiology and genetics. Baboons have large skulls with long protruding facial structures (maxilla and mandible). These craniofacial traits distinguish baboons from other closely related primates, and also differ to a lesser extent among baboon species. Understanding the genetic basis of evolutionary change in craniofacial morphology among baboons has implications for other primate species, because many different species differ in the size and shape of their skulls. Skull morphology is obviously quite different in humans as compared to our closest primate relatives, the great apes. Thus, identifying specific genes and genetic mechanisms that influence differences in the size and shape of the baboon skull can provide new insights into some of the genes and genetic processes that may have been involved in the evolution of the human skull and that of other primates. In this project, we examined the size and shape of skulls from 985 baboons (genus Papio). These baboons were bred and housed at the Southwest National Primate Research Center, San Antonio. In addition, the pedigree relationships or genealogy for these animals was known, so that by comparing these animals and correlating anatomical differences with pedigree relationships it is possible to determine the degree to which genetic differences influence particular traits (i.e. whether genetic differences affect particular patterns in skull size and shape). We collected the skulls of 985 baboons at the time of death, and used CT scanning methods to generate 3-D images of the bones that make up each skull. These very accurate images were used to make a series of measurements and to quantify individual variation in skull size and shape, based on the locations of specific boney landmarks. We then used a series of statistical and molecular genetic analyses to determine which measurements were significantly influenced by genetic differences among the baboons, and to begin to identify specific genes that account for these differences. Using linkage analysis to identify chromosomal segments that carry the important genes, and then DNA sequencing and association analysis to identify specific genes within those regions, we were able to show that a specific gene (HAND2) exerts a significant influence on several measurements related to the length and shape of the baboon maxilla. These measurements of the maxilla account for substantial variation in the overall size and shape of the baboon skulls. Thus, this project has produced several new and meaningful types of information. First, we produced a database of morphological measurements from a large population of baboons. This is the largest such database of craniofacial measurements for a pedigreed set of nonhuman primates. This database is being shared with other researchers, so that others can also make use of the information we have generated. Second, we were able to identify an extensive series of craniofacial traits (both measurements of size/shape and other features of the bony anatomy) that show significant heritability, i.e. show clear evidence that genetic differences among the animals influence the observed morphological differences. Third, we used statistical methods to demonstrate that a specific gene (HAND2) is associated with individual variation in specific measurements of the face. Finally, we have created a large collection of cleaned and prepared baboon skulls that are available for any researcher to use in future studies of their own. We also created a large set of digital CT scan images of those same skulls. Those images can be used for research without going back to the skulls themselves. This project has increased our knowledge of the genetic causes of individual variation in skull size and shape. It also generated new hypotheses concerning particular genes that may have played a significant part in the evolution of skull size and shape in various primate species, including humans.
