On its 125th anniversary, Science magazine posed 125 unsolved scientific questions, among which "What genetic changes made us uniquely human?" was listed as one of the 25 core problems. Yet the divergence rate between the alignable genomes of humans and chimpanzees is as little as 1.23%. Scientists hypothesized that gene regulation might account for their dramatic phenotypic differences.
Recently, Quantitative Biology published a research article entitled "The human intelligence evolved from proximal cis-regulatory saltations" in which the focus shifted from protein sequences to their regulatory regions. They represented proximal regulatory sequences of genes using the cis-regulatory element frequency (CREF) matrix. The transcriptional regulatory information from humans and extant ape species—such as chimpanzees, bonobos, and gorillas—was transformed into orthogonal modules that could be aligned and compared.
The researchers extracted 10 principal regulatory modules from the whole-genome data and ranked them in descending order of binding energy. By comparing the CREF modules of four hominid species, they discovered that two regulatory modules underwent saltations: one between the 4th and 5th eigen-levels and another between the 9th and 10th. The newly regulated gene targets include those associated with long-term memory, cochlea development, learning, exploration behavior, social behavior, and regulation of sleep and happiness. Without any a priori, the CREF module can largely explain the saltation of human cognition and intelligence, offering a new quantitative paradigm for studying the evolution of gene regulation.
