Adaptation and mal-adaptation to ambient hypoxia; Andean, Ethiopian and Himalayan patterns.
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.
Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
Guoqiang
G
Xing
Clifford
C
Qualls
Luis
L
Huicho
Maria
M
Rivera-Ch
Maria
M
River-Ch
Tsering
T
Stobdan
Marat
M
Slessarev
Eitan
E
Prisman
Shoji
S
Ito
Soji
S
Ito
Hong
H
Wu
Angchuk
A
Norboo
Diskit
D
Dolma
Moses
M
Kunzang
Tsering
T
Norboo
Jorge L
JL
Gamboa
Victoria E
VE
Claydon
Joseph
J
Fisher
Guta
G
Zenebe
Amha
A
Gebremedhin
Roger
R
Hainsworth
Ajay
A
Verma
Otto
O
Appenzeller
D000222:Adaptation, Physiological / Q000235:genetics*; D000531:Altitude; D000532:Altitude Sickness / Q000235:genetics* / Q000503:physiopathology; D015331:Cohort Studies; D005002:Ethiopia; D000860:Hypoxia / Q000235:genetics* / Q000503:physiopathology; D009390:Nepal; D010568:Peru