Meeting Abstract
We used a comparative approach to understanding differential disease susceptibilities between closely related species. Humans and chimpanzees are separated by approximately 4-6 million years of evolution, but have very different phenotypic traits, including the susceptibilities to a number of diseases. We tested one of these disease phenotypes, epithelial cancer progression, in cell culture. Previously, we found that many of the genes involved in this pathway show signals of positive selection in putative cis-regulatory regions. Presumably these changes are advantageous at other life-history timepoints. Other studies have shown that when human fibroblasts are starved and then exposed to serum, they undergo a transcriptional response that involves categories of genes that are highly correlated with gene expression signatures found in human epithelial cancers. We have now performed this same experiment on human and chimpanzee cell lines, using RNA-Seq and DNase-Seq (a measure of open chromatin) to understand how these species react differently to this important physiological response. Our results suggest that there are a few important gene expression pathways that have changed over evolutionary time to respond to this stressor and there have also been significant changes in enhancer usage over evolutionary time. This experiment provides insights into the genetic pathways underlying the known differences in carcinoma rates between humans and chimpanzees.
