Genetic variation and ethnicity yield differences in gene expression patterns of human macrophages after infection with different bacterial pathogens. In this study we test for the effects of African versus European ancestry on the transcriptional response of primary macrophages to live bacterial pathogens. By integrating ancestry-related differences in macrophage response to infection with genetic and evolutionary analyses, we address three fundamental questions: (i) the degree to which innate immune responses are differentiated between European and African ancestry individuals; (ii) the genetic variants that account for such differences; and (iii) the evolutionary mechanisms (neutral genetic drift vs positive selection) that led to their establishment in modern human populations, including introgression of Neanderthal genetic traits in individuals with European ancestry.
- Y. Nédéléc1, J. Sanz1, G. Baharian1, Z.A. Szpiech, A. Pacis, A. Dumaine, J.C. Grenier, A. Freiman, J. Sams, S. Hebert, A. Pagé-Sabourin, F. Luca, R. Blekhman, R.D. Hernández, R. Piqué-Regi, J. Tung, V. Yotova & L.B.B. Barreiro, (1 co-first author). Genetic ancestry and natural selection drive population differences in immune responses to pathogens. Cell 167-3, p657–669.e21 (2016) (article and issue cover -artwork by Barreiro lab, E. Choi and S. Knemeyer-.)
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