Abstract
The divergence rate between the alignable genomes of humans and chimpanzees is as little as 1.23%. Their phenotypical difference was hypothesized to be accounted for by gene regulation. We construct the cis-regulatory element frequency (CREF) matrix to represent the proximal regulatory sequences for each species. Each CREF matrix is further decomposed into dual eigen-modules. By comparing the CREF modules of four existing hominid species, we examine their quantitative and qualitative changes along evolution. We identified two saltations: one between the 4th and 5th, the other between the 9th and 10th eigen-levels. The cognition and intelligence unique to humans are thus found from the saltations at the molecular level. They include long-term memory, cochlea/inner ear morphogenesis that enables the development of human language/music, social behavior that allows us to live together peacefully and to work collaboratively, and visual/observational/associative learning. Moreover, we found exploratory behavior crucial for humans' creativity, the GABA-B receptor activation that protects our neurons, and serotonin biosynthesis/signaling that regulates our happiness. We observed a remarkable increase in the number of motifs present on Alu elements on the 4th/9th motif-eigenvectors. The cognition and intelligence unique to humans can, by and large, be identified using only the CREF profiles without any a priori. Although gradual evolution might be the only mode in the mutations of protein sequences, the evolution of gene regulation has both gradual and saltational modes, which could be explained by the framework of CREF eigen-modules.