Mechanisms of Human Gene Evolution.

Abstract

“What makes us humans?” is one of the most fascinating questions in evolution. Investigating human genetic variations within the context of primates will provide valuable information about the development and function of important primate features and unique human features. In Chapter 1 and 2, I conducted detailed evolutionary studies on two homeobox genes, TGIFLX and ESX1. Evolutionary analysis provided evidence for positive selection acting on the two genes during primate evolution. The identification of non-conserved homeobox genes is interesting, because such homeobox genes may regulate important developmental processes that vary among relatively closely related species. TGIFLX and ESX1 are located on X chromosome and involved in male spermatogenesis process. The finding of positive selection in these genes suggests that even in the recent past of human and primate evolution, spermatogenesis has been subject to adaptive modifications. Gene loss is an important source of human-specific genetic change. Genes related to chemoreception and immunity account for a large proportion of lost genes in the human lineage. In Chapter 3, I reported the relaxation of selective constraint and loss of function in the evolution of human bitter taste receptor genes, probably due to the change in diet, use of fire, and reliance on other means of toxin avoidance that emerged in human evolution. This finding provided further evidence for reduced sensory capabilities of humans in comparison to many other mammals. Gene loss or pseudogenization has also been proposed to serve as an engine of evolutionary change, especially during human origins (the “less-is-more” hypothesis). In Chapter 4, I focused on CASPASE12, a cysteinyl aspartate proteinase participating in inflammatory and innate immune response to endotoxins. My results provided population genetic evidence that the nearly complete fixation of a null allele at CASPASE12 has been driven by positive selection, probably because the null allele confers protection from severe sepsis. Furthermore, the identification and analysis of human-specific pseudogenes open the door for understanding the roles of gene losses in human origins, and the demonstration that gene loss itself can be adaptive supports and extends the ‘‘less-is-more’’ hypothesis.