Science Advances 27 Nov 2020:
Vol. 6, no. 48, eabc9863
A longstanding hypothesis is that divergence between humans and chimpanzees might have been driven more by regulatory level adaptations than by protein sequence adaptations. This has especially been suggested for regulatory adaptations in the evolution of the human brain. We present a new method to detect positive selection on transcription factor binding sites on the basis of measuring predicted affinity change with a machine learning model of binding. Unlike other methods, this approach requires neither defining a priori neutral sites nor detecting accelerated evolution, thus removing major sources of bias. We scanned the signals of positive selection for CTCF binding sites in 29 human and 11 mouse tissues or cell types. We found that human brain–related cell types have the highest proportion of positive selection. This result is consistent with the view that adaptive evolution to gene regulation has played an important role in evolution of the human brain.
With only 1 percent difference, the human and chimpanzee protein-coding genomes are remarkably similar. Understanding the biological features that make us human is part of a fascinating and intensely debated line of research. Researchers have developed a new approach to pinpoint adaptive human-specific changes in the way genes are regulated in the brain.