Population,genetics and human immunity: the interferon paradigm

作者：Manry Jeremy^*; Quintana Murci Lluis

来源：Medecine Sciences, 2012, 28(12): 1095-1101.

DOI：10.1051/medsci/20122812020

Population genetics and human immunity: the interferon paradigm The evolutionary genetics dissection of immunity-related genes provides insights into immunological defence mechanisms and highlight host pathways playing an important role in pathogen resistance. Recent population genetic data have increased knowledge of the biological relevance of human interferons (IFN), cytokines released by host cells in response to pathogen presence or tumour cells. Some IFN-alpha subtypes as well as IFN-gamma are strongly evolutionarily constrained, suggesting that the functions they fulfil are essential and non redundant. Other IFN, the most extreme cases being IFN-alpha 10 and IFN-epsilon, can accumulate missense or nonsense mutations at high population frequencies, suggesting higher redundancy. Furthermore, genetic variation at some IFN genes can be advantageous for the host and increase in frequency by positive selection. This has been shown for type III IFN, where mutations at at IL28A, IL288 and IL29 have been positively selected in Europeans and Asians, most likely by increasing resistance to viral infection. This review uses the IFN paradigm to illustrate the value of the evolutionary approach in highlighting important determinants of host immune responsiveness in the natural setting.

• 出版日期2012-12