The evolution and differentiation of species is often accompanied by gene duplication events, which serve as a major mechanism creating new genes and expanding existing and gene families. Among primates, including humans, such changes have resulted in a large number of primate-specific genes or expanded gene families, some of which are related to certain phenotypic traits likely important to the features the set primates apart. Unfortunately, these are not always positive phenotypic traits. For example, cancer/testis (CT) antigens encoded by germline genes are often aberrantly expressed in a number of cancers afflicting humans, but also non-human primates.
Previous researchers noted that CT antigens are frequently involved in gene families that are highly expressed in germ cells, as well as trophoblast and tumor cells. Expanding on this observation, Bing Su of the Kunming Institute of Zoology (KIZ), Chinese Academy of Sciences (CAS) undertook an evolutionary analysis of the CTAGE (cutaneous T cell lymphoma-associated antigen) gene family, to examine its molecular history and functional significance over the course primate evolution. Comparing CTAGE genes from humans, chimpanzees, gorillas, orangutans, macaques, marmosets and other mammals, Bing’s team found a rapid and primate specific expansion of CTAGE family, continuing on to humans, suggesting some functional role in human evolution.
The connection of the CT antigens to humans is especially interesting given that cancer is globally a major health concern, leading to some 8 million deaths a year worldwide. Previous studies suggested that CT antigens contribute to neoplastic phenotypes and oncogenesis via germline gene-expression, but it was not clear whether the CTAGE family was evolving under positive selection or had experienced a human specific expansion. Several earlier studies noted that non-human primates have low cancer incidence rate, ostensibly due to genetic differences between humans and non-human primates. However, a sequence comparison of 333 human cancer genes with orthologs form chimpanzees showed a high degree of conservation and limited genetic differences might theoretically account for different cancer susceptibility between humans and our closest non-human primate cousins. If so, it is possible that human-specific copy number gains of CTAGE genes, or in general gene copy number changes, may be potentially fruitful avenues for exploring the relatively high rates of cancer among humans.
Though the results from Bing Su’s current study are preliminary, they do extend the existing knowledge on human evolution, and offer some provocative insights into future biomedical research aimed at understanding certain human-specific risk factors for cancer, which may eventually pave the way for more effective animal models, or even the development of novel therapeutics.
The complete study was recently published in Molecular Biology and Evolution, available online at: http://mbe.oxfordjournals.org/content/early/2014/06/09/molbev.msu188.full.pdf+html