(Photo by Leanne
Nash)
The evolutionary significance of copy number variation on the human and chimpanzee sex chromosomes
AC Stone (co-PI)
It has recently been recognized that copy number variants (CNVs; large duplications and deletions of genomic sequence) are common among normal humans. Some of these variants are likely involved in human phenotypic diversity, including traits of longstanding interest to anthropologists. Additionally, between-species copy number differences have had a greater per base impact than single nucleotide substitutions on genomic differences between humans and chimpanzees, and between-species copy number variation may have contributed to the evolution of phenotypes that distinguish us from our closest relatives. The goal of this study is to gain an understanding of the structure and evolution of genomic copy number variation in primates and its impact on gene expression. Specifically, we will (i) assess whether levels and patterns of copy number variation in non-human primates are similar to those for humans and test for heterogeneity in the inter-specific fixation rate for copy number gains and losses, and (ii) characterize the relationship between copy number variants (CNVs) and gene expression variation across different timescales of primate evolution. Our work will provide the most comprehensive understanding to date of the relationship between copy number and gene expression variation in primates, allowing us to identify specific CNVs that may be of considerable evolutionary and biomedical significance. Our research team includes Dr. Charles Lee (PI, Brigham and Womens Hospital, Harvard University), Dr. Yoav Gilad (Co-PI, University of Chicago), leaders in both the primate copy number variation and gene expression fields.
This project is funded by the National Institutes of Health (1R01GM081533-01A1).
Recombination and Population History in Pan
AC Stone (co-PI)
Recombination is responsible for the generation and shuffling of variation in the genome of most organisms. Therefore, understanding how certain historical events influence recombination patterns is a fundamental question for studying primate diversity in general and human diversity in particular. DNA sequence data can tell us about how processes like historical adaptation or changes in population size and growth generate different patterns of recombination in the genome. Some research shows that recombination rates can vary dramatically across the genome, even in the same genomic regions between humans and chimpanzees. Therefore, recombination rates may change over very short periods of time, which can have implications for how genetic variation accumulates and leads to differentiation within and between humans over time. In this respect, a sampling of more closely related primates is needed to address how rapid these recombination rate patterns change given that the divergence time of 5-7 MY between humans and chimpanzees may be too distant. In addition, most of the previous data have come from studies of gene regions or collections of disease markers or from samples of chimpanzee individuals from the same family. These samples of gene regions and related individuals are biased and may have largely influenced our general understanding of how recombination rates vary over random regions of the human genome. To address these issues, this project will sample 20 genome regions (each of ~15,000 nucleotides in size), which do not have protein-coding genes, in population samples of unrelated western chimpanzees (Pan troglodytes verus) and bonobos (Pan paniscus), which are estimated to have diverged ~0.9-1.8 million years (MY) ago. Analyses of population structure, correlations among DNA mutations, and patterns of natural selection, between the genomes of these closely related primates will enable us to test hypotheses about how recombination patterns change over short periods of time in the human genome. This project is a collaboration with Dr. Brian Verrelli (PI, Arizona State University).
This research is being supported by the National Science Foundation (BCS-07115972)
Previous research:
Y chromosome variation in chimpanzees and bonobos
AC Stone (PI)
Past DNA studies have suggested that chimpanzee population history has been surprisingly different from humans, although chimpanzees are our nearest relatives. Unfortunately the fossil record for chimpanzees is virtually nonexistent and, thus, genetic investigation of present populations is the best method to examine this history. Chimpanzees are, however, highly endangered and the window of opportunity to sample their genetic diversity may be rapidly closing. To date, genetic investigations have been limited, and they have focused primarily on the maternally-inherited mitochondrial DNA. The goal of this project is to search for variation on the Y chromosomes of chimpanzees, including Pan troglodytes, (the chimpanzee) and Pan paniscus (the pygmy chimpanzee or bonobo). This will provide a new perspective to test hypotheses about population history both within and between chimpanzee species. In addition, it will allow the comparison of chimpanzee and human demographic histories and, thus, can shed light on our own evolutionary history. We are also investigating Y chromosome evolutionary history in the great apes and humans. Because the chimpanzee Y chromosome is 25% smaller than the human Y and may have been subject to structural rearrangement, it is evident that the chimpanzee Y chromosome has undergone interesting changes since diverging from the ancestral human-chimpanzee Y chromosome. Finally, we hope to identify subspecies specific Y chromosome markers within Pan troglodytes that, when combined with mitochondrial DNA data, will allow the origins of the captive population to be clarified.
This research was supported by the National Science Foundation (BCS-0073871)
To learn more about chimpanzees and bonobos, check the
following links:
The Wisconsin Regional Primate Research Center
The Bonobo Conservation Initiative
