Abstract

The study of the biology of evolution has been confined to laboratories and model organisms. However, controlled laboratory conditions are unlikely to model variations in environments that influence selection in wild populations. Thus, the study of "fitness" for survival and the genetics that influence this are best carried out in the field and in matching environments.

Therefore, we studied highland populations in their native environments, to learn how they cope with ambient hypoxia. The Andeans, African highlanders and Himalayans have adapted differently to their hostile environment.

Chronic mountain sickness (CMS), a loss of adaptation to altitude, is common in the Andes, occasionally found in the Himalayas; and absent from the East African altitude plateau.

We compared molecular signatures (distinct patterns of gene expression) of hypoxia-related genes, in white blood cells (WBC) from Andeans with (n = 10), without CMS (n = 10) and sea-level controls from Lima (n = 20) with those obtained from CMS (n = 8) and controls (n = 5) Ladakhi subjects from the Tibetan altitude plateau. We further analyzed the expression of a subset of these genes in Ethiopian highlanders (n = 8). In all subjects, we performed the studies at their native altitude and after they were rendered normoxic.

We identified a gene that predicted CMS in Andeans and Himalayans (PDP2). After achieving normoxia, WBC gene expression still distinguished Andean and Himalayan CMS subjects.

Remarkably, analysis of the small subset of genes (n = 8) studied in all 3 highland populations showed normoxia induced gene expression changes in Andeans, but not in Ethiopians nor Himalayan controls. This is consistent with physiologic studies in which Ethiopians and Himalayans show a lack of responsiveness to hypoxia of the cerebral circulation and of the hypoxic ventilatory drive, and with the absence of CMS on the East African altitude plateau.

Document Type

Article

Publication Date

6-4-2008

Notes/Citation Information

Published in PLoS ONE, v. 3, no. 6, e2342.

© 2008 Xing et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Formal Correction: This article has been formally corrected to address the following errors.

  1. The fourth author's name appears incorrectly. It should be: Maria Rivera-Ch. The correct citation should read: Xing G, Qualls C, Huicho L, Rivera-Ch M, Stobdan T, et al. (2008) Adaptation and Mal-Adaptation to Ambient Hypoxia; Andean, Ethiopian, and... (read formal correction)
  2. The eighth author's name appears incorrectly. It should be: Shoji Ito (read formal correction)

Digital Object Identifier (DOI)

http://dx.doi.org/10.1371/journal.pone.0002342

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