Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: functional implications
| Autor: | Laelia Pinto, Laurie Burdett, Eduardo Tarazona-Santos, Stephen J. Chanock, Latife Pereira, Wagner C. S. Magalhães, Fernanda Lyon, Renee Chen, Cristina Fabbri, Rodrigo A. F. Redondo, Andrew Crenshaw, Meredith Yeager, Moara Machado, Ben Sestanovich |
|---|---|
| Přispěvatelé: | E. Tarazona-Santo, M. Machado, W. C. S. Magalhae, R. Chen, F. Lyon, L. Burdett, A. Crenshaw, C. Fabbri, L. Pereira, L. Pinto, R. A. F. Redondo, B. Sestanovich, M. Yeager, S. J. Chanock |
| Rok vydání: | 2013 |
| Předmět: |
Molecular Sequence Data
Black People Biology chronic granulomatous disease Granulomatous Disease Chronic White People immunogenetic Evolution Molecular Chronic granulomatous disease Asian People Bacterial Proteins Genetics medicine Animals Humans CYBB Amino Acid Sequence Selection Genetic Molecular Biology Gene innate immunity Ecology Evolution Behavior and Systematics Phylogeny Discoveries Innate immune system Natural selection NADPH oxidase Membrane Glycoproteins Bacteria Haplotype Genetic Variation NADPH Oxidases Bacterial Infections medicine.disease Catalase Haplotypes Host-Pathogen Interactions Mutation NADPH Oxidase 2 biology.protein Function (biology) |
| Zdroj: | Molecular biology and evolution. 30(9) |
| ISSN: | 1537-1719 |
| Popis: | The phagocyte NADPH oxidase catalyzes the reduction of O-2 to reactive oxygen species with microbicidal activity. It is composed of two membrane-spanning subunits, gp91-phox and p22-phox (encoded by CYBB and CYBA, respectively), and three cytoplasmic subunits, p40-phox, p47-phox, and p67-phox (encoded by NCF4, NCF1, and NCF2, respectively). Mutations in any of these genes can result in chronic granulomatous disease, a primary immunodeficiency characterized by recurrent infections. Using evolutionary mapping, we determined that episodes of adaptive natural selection have shaped the extracellular portion of gp91-phox during the evolution of mammals, which suggests that this region may have a function in host-pathogen interactions. On the basis of a resequencing analysis of approximately 35 kb of CYBB, CYBA, NCF2, and NCF4 in 102 ethnically diverse individuals (24 of African ancestry, 31 of European ancestry, 24 of Asian/Oceanians, and 23 US Hispanics), we show that the pattern of CYBA diversity is compatible with balancing natural selection, perhaps mediated by catalase-positive pathogens. NCF2 in Asian populations shows a pattern of diversity characterized by a differentiated haplotype structure. Our study provides insight into the role of pathogen-driven natural selection in an innate immune pathway and sheds light on the role of CYBA in endothelial, nonphagocytic NADPH oxidases, which are relevant in the pathogenesis of cardiovascular and other complex diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|