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Evolution of the primate trypanolytic factor APOL1

2014; National Academy of Sciences; Volume: 111; Issue: 20 Linguagem: Inglês

10.1073/pnas.1400699111

1091-6490

Russell Thomson, Giulio Genovese, Chelsea M. Canon, Daniella Kovacsics, Matthew K. Higgins, Mark Carrington, Cheryl A. Winkler, Jeffrey B. Kopp, Charles N. Rotimi, Adebowale Adeyemo, Ayo P. Doumatey, George Ayodo, Seth L. Alper, Martin R. Pollak, David J. Friedman, Jayne Raper,

Lysosomal Storage Disorders Research

Significance African trypanosomes are parasites that can cause African sleeping sickness in humans. Humans and some primates, but not other mammals, have a gene called APOL1 that protects against certain trypanosomes. Genetic variants in APOL1 that arose in Africa are strongly associated with kidney disease in African Americans. These kidney disease-associated variants may have risen to high frequency in Africa because they can defend humans against a particularly pathogenic trypanosome. In this paper, we show how APOL1 has evolved by analyzing the distribution of these variants in Africa and then elucidating the molecular mechanisms that enhance their trypanosome killing capacity. We also show that these antitrypanosomal APOL1 variants may have adverse consequences for the host.