---
_id: '508'
abstract:
- lang: eng
  text: The phagocyte NADPH oxidase catalyzes the reduction of O2 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.
article_processing_charge: No
author:
- first_name: Eduardo
  full_name: Tarazona Santos, Eduardo
  last_name: Tarazona Santos
- first_name: Moara
  full_name: Machado, Moara
  last_name: Machado
- first_name: Wagner
  full_name: Magalhães, Wagner
  last_name: Magalhães
- first_name: Renee
  full_name: Chen, Renee
  last_name: Chen
- first_name: Fernanda
  full_name: Lyon, Fernanda
  last_name: Lyon
- first_name: Laurie
  full_name: Burdett, Laurie
  last_name: Burdett
- first_name: Andrew
  full_name: Crenshaw, Andrew
  last_name: Crenshaw
- first_name: Cristina
  full_name: Fabbri, Cristina
  last_name: Fabbri
- first_name: Latife
  full_name: Pereira, Latife
  last_name: Pereira
- first_name: Laelia
  full_name: Pinto, Laelia
  last_name: Pinto
- first_name: Rodrigo A
  full_name: Fernandes Redondo, Rodrigo A
  id: 409D5C96-F248-11E8-B48F-1D18A9856A87
  last_name: Fernandes Redondo
  orcid: 0000-0002-5837-2793
- first_name: Ben
  full_name: Sestanovich, Ben
  last_name: Sestanovich
- first_name: Meredith
  full_name: Yeager, Meredith
  last_name: Yeager
- first_name: Stephen
  full_name: Chanock, Stephen
  last_name: Chanock
citation:
  ama: 'Tarazona Santos E, Machado M, Magalhães W, et al. Evolutionary dynamics of
    the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: Functional implications.
    <i>Molecular Biology and Evolution</i>. 2013;30(9):2157-2167. doi:<a href="https://doi.org/10.1093/molbev/mst119">10.1093/molbev/mst119</a>'
  apa: 'Tarazona Santos, E., Machado, M., Magalhães, W., Chen, R., Lyon, F., Burdett,
    L., … Chanock, S. (2013). Evolutionary dynamics of the human NADPH oxidase genes
    CYBB, CYBA, NCF2, and NCF4: Functional implications. <i>Molecular Biology and
    Evolution</i>. Oxford University Press. <a href="https://doi.org/10.1093/molbev/mst119">https://doi.org/10.1093/molbev/mst119</a>'
  chicago: 'Tarazona Santos, Eduardo, Moara Machado, Wagner Magalhães, Renee Chen,
    Fernanda Lyon, Laurie Burdett, Andrew Crenshaw, et al. “Evolutionary Dynamics
    of the Human NADPH Oxidase Genes CYBB, CYBA, NCF2, and NCF4: Functional Implications.”
    <i>Molecular Biology and Evolution</i>. Oxford University Press, 2013. <a href="https://doi.org/10.1093/molbev/mst119">https://doi.org/10.1093/molbev/mst119</a>.'
  ieee: 'E. Tarazona Santos <i>et al.</i>, “Evolutionary dynamics of the human NADPH
    oxidase genes CYBB, CYBA, NCF2, and NCF4: Functional implications,” <i>Molecular
    Biology and Evolution</i>, vol. 30, no. 9. Oxford University Press, pp. 2157–2167,
    2013.'
  ista: 'Tarazona Santos E, Machado M, Magalhães W, Chen R, Lyon F, Burdett L, Crenshaw
    A, Fabbri C, Pereira L, Pinto L, Fernandes Redondo RA, Sestanovich B, Yeager M,
    Chanock S. 2013. Evolutionary dynamics of the human NADPH oxidase genes CYBB,
    CYBA, NCF2, and NCF4: Functional implications. Molecular Biology and Evolution.
    30(9), 2157–2167.'
  mla: 'Tarazona Santos, Eduardo, et al. “Evolutionary Dynamics of the Human NADPH
    Oxidase Genes CYBB, CYBA, NCF2, and NCF4: Functional Implications.” <i>Molecular
    Biology and Evolution</i>, vol. 30, no. 9, Oxford University Press, 2013, pp.
    2157–67, doi:<a href="https://doi.org/10.1093/molbev/mst119">10.1093/molbev/mst119</a>.'
  short: E. Tarazona Santos, M. Machado, W. Magalhães, R. Chen, F. Lyon, L. Burdett,
    A. Crenshaw, C. Fabbri, L. Pereira, L. Pinto, R.A. Fernandes Redondo, B. Sestanovich,
    M. Yeager, S. Chanock, Molecular Biology and Evolution 30 (2013) 2157–2167.
date_created: 2018-12-11T11:46:52Z
date_published: 2013-09-01T00:00:00Z
date_updated: 2025-09-30T07:13:08Z
day: '01'
department:
- _id: JoBo
doi: 10.1093/molbev/mst119
external_id:
  isi:
  - '000323616600014'
  pmid:
  - '23821607'
intvolume: '        30'
isi: 1
issue: '9'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748357/
month: '09'
oa: 1
oa_version: Submitted Version
page: 2157 - 2167
pmid: 1
publication: Molecular Biology and Evolution
publication_status: published
publisher: Oxford University Press
publist_id: '7310'
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and
  NCF4: Functional implications'
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 30
year: '2013'
...