Poster Presentation Society for Molecular Biology and Evolution Conference 2016

Diversity in gene expression in cell populations in relation to the selectionism view of tumor evolution (#419)

Chunyan Li 1 , Yali Hou 1 , Jin Xu 1 , Aiqun Zhang 2 , Jiahong Dong 2 3 , Chung-I Wu 1 4 , Xuemei Lu 1
  1. Beijing Institute of Genomics, Chinese Academy of Sciences, Chao Yang, Beijing 100101, China
  2. Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijng 100853, China
  3. Department of Hepatopancreatobiliary Surgery, Beijing Tsinghua Changgung Hospital, Medical Center, Tsinghua University, Beijing, China
  4. Department of Ecology and Evolution, University of Chicago, Chicago IL, USA

While intratumor diversity driven by selection has been the prevailing view in cancer biology, pervasive selection generally does not lead to the high genetic diversity observed within a single tumor. Indeed, recent population genetic analyses of intratumor diversity have been unable to reject the neutral interpretation and it seems necessary to test the selectionism view directly. Here, we utilized gene expression data as surrogate for functional significance in intra- and inter-tumor comparisons. Selectively-driven expression divergence is expected to be higher than neutral expression divergence. Instead, we observed little expression differentiation among samples of the same tumors, which is even lower than the expression differences among normal samples, the latter being the baseline level of neutral divergence. To further test the hypothesis of neutral evolution, we selected a tumor that is unusually diverse in both nucleotide variation and chromosomal alteration for detailed studies. This case enables us to calibrate the level of expression divergence against that of genetic divergence. We observe that intratumor divergence in gene expression profile lags far behind genetic divergence, indicating insufficient phenotypic differences for selection to operate. All these analyses suggest that natural selection does not operate effectively within tumors. The evolutionary as well as medical implications are discussed.