Doubling Resistance

Science's STKE  08 Mar 2005:
Vol. 2005, Issue 274, pp. tw91
DOI: 10.1126/stke.2742005tw91

Segmental duplications within the genome are fundamental to both human disease and evolution. Because certain duplications span genes involved in immune defense, some differences in the ability to fight infections can be attributable to dosage effects resulting from the number of copies of specific genes. Gonzalez et al. (see the Perspective by Nolan et al.) noted differences in segmental duplications spanning the variant of the CCL3 chemokine, CCL3L1, in different ethnic and geographic populations. The CCL3 receptor, CCR5, is an important coreceptor for human immunodeficiency virus-1 (HIV-1) infection. The authors found that increased segmental duplications increased resistance to acquiring HIV-1 and progression to AIDS, and correlated with CCL3L1 expression, levels of CCR5, and reduced CD4+ T cell decline. Similar duplications in chimpanzees suggest that some duplications may be an ancient adaptive response of the immune system to environmental pressures.

E. Gonzalez, H. Kulkarni, H. Bolivar, A. Mangano, R. Sanchez, G. Catano, R. J. Nibbs, B. I. Freedman, M. P. Quinones, M. J. Bamshad, K. K. Murthy, B. H. Rovin, W. Bradley, R. A. Clark, S. A. Anderson, R. J. O'Connell, B. K. Agan, S. S. Ahuja, R. Bologna, L. Sen, M. J. Dolan, S. K. Ahuja, The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 307, 1434-1440 (2005). [Abstract] [Full Text]

D. Nolan, I. James, S. Mallal, HIV: Experiencing the pressures of modern life. Science 307, 1422-1424 (2005). [Summary] [Full Text]