One of the most exciting challenges in contemporary science is uncovering the genetic basis for the origin of uniquely human traits. Humans and other great apes are genetically very similar, yet diverse aspects of human anatomy, physiology, and behavior are markedly distinct. Recent technological developments provide the ability to begin identifying the specific genes that underlie these important trait differences. This project will focus on the evolution of human diet. Dietary traits are particularly interesting because the diet of early human ancestors and modern humans differ so markedly from those of the other great apes and because diet affects so many aspects of human health and disease. An interdisciplinary team of anthropologists and human geneticists will integrate genetic, organismal, and ecological information to better understand the genetic basis for the evolution of dietary traits in humans.
The primary intellectual goals of this project are to: (1) screen the human genome for relevant genes using two approaches, measuring gene expression across the entire genome from humans and chimpanzees in several tissues of dietary significance using ultra high-throughput sequencing and testing for adaptation in DNA sequences across the entire genome based on patterns of mutation; (2) conduct integrative case studies of diet-related genes implicated in trait changes during human origins through extensive DNA sequence comparisons among great ape species, detailed characterization of gene expression, experimental tests of functional differences, and associations between gene expression and specific dietary traits; and (3) conduct integrative case studies of diet-related genes among modern African human populations that are diverse with respect to diet and local climate, through detailed analyses of genetic variation, tests for natural selection, and genetic associations with specific dietary traits.
The broader impacts of this research include: collaborations and resource building with African scientists, recruitment and training of women and minority trainees, education outreach to grade school students, building two novel and informative databases that will be easily accessible through the web, and developing software for comparative analysis of primate genome sequences and gene expression.
Humans are unique among the great apes in having a highly omnivorous diet. The increased intake of fats and proteins, in particular, were likely important for the evolution of our much larger brain. We also consume much more starchy food than other great apes. Importantly, our unique diet also exposes us to disease risks that are different from those of our closest living relatives, including chimpanzees. Thus, knowing how diet changed during human origins may provide insights into the origin of the distinctive features of humans as a species, including practical knowledge about medical conditions. Yet little detailed information about how our diet changed was available prior to the beginning of this project. The goal of our project was to learn more about the specific genetic changes that made possible the evolution of unique features of the human diet. In order to identify candidate genes, we compared genome sequences and gene expression between humans and chimpanzees. These analyses identified dozens of genes whose function appears to differ between the two species. As expected, many of these genes code for proteins involved in how the body extracts, transports, stores, and utilizes specific components in food. More specifically, this list of genes parallels the shift in diet, in that many of them code for proteins that process fats and starches. Additional genes are related to other biological processes with more indirect, yet equally important, connections to diet. For instance, two of the genes affect tooth development, and may contribute to the thicker enamel and altered cusp shape of human teeth. From our list of candidate genes, we followed up with detailed studies on more than 25. This allowed us to learn more about how changes in the function of specific genes may have affected other dietary traits. For instance, we found that humans produce more of two specific enzymes that use animal fats to build key components of the cell membranes of nerve cells in the brain. The diet of chimpanzees has only small amounts of these raw materials, but the omnivorous diet of humans provides them in abundance. We hypothesize that the change in enzyme activity took advantage of this new resource during the paleolithic (stone age), providing the materials for the evolution of a larger brain. Interestingly, what was originally a useful trait later became a liability when humans switched to starch-rich diets following the agricultural revolution. Grains contain large amounts of oleic acid, which these same two enzymes convert into a compound that triggers inflammation. We hypothesize that this gene-by-environment mismatch contributes to the uniquely human incidence of several inflammation-based diseases, including type II diabetes and atherosclerosis. We have presented our findings from this project in several talks to school groups, the general public, and science journalists. We also mentored 12 undergraduate students during the course of this project. These students received training in cutting-edge genomic and computational approaches to biomedical research. Most have gone on to medical school, dental school, graduate school, or private industry, where their training in these methods is of direct use. We have now published 22 studies in scholarly journals and presented our results at several national and international conferences. Finally, we developed genomic and computational methods during the course of this project that are useful for other areas of research in genomics and genetics.
