Adaptation and Mal-Adaptation to Ambient Hypoxia; Andean, Ethiopian and Himalayan Patterns

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.

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

“…In this context, it is interesting to note that in addition to HD, another commonly observed hallmark exhibited by high-altitude sojourners is erythropoiesis, which increases red blood cell mass and blood viscosity (419, 420). However, despite such long-term enhancements to oxygen delivery systems during prolonged hypoxic exposure, HD persists, and physical and mental performance for most lowland peoples is impaired during prolonged exposures to hypoxia at altitude (418, 422, 424). Furthermore, individuals from low-altitude populations who migrate to high altitude suffer from a number of hypoxia-related diseases and struggle to reproduce at these elevations (178, 209, 266, 421).…”

The epigenetic side of human adaptation: hypotheses, evidences and theories

“…For instance, physiological modifications are optimal shortterm adaptive mechanisms, resulting instead in potentially deleterious long-term ones due to the possibility of causing damage to the organism. One clear example is that of adaptation to high altitude (Xing et al, 2008), in which physiological changes, such as increased heart rate, may be decisive for short-term survival, but finally can cause severe tissue and organ damage. Interestingly, epigenetics mechanisms could represent ''medium-term'' strategies to cope with a demanding environmental condition, such as high altitude hypoxia.…”

Higher androgen bioactivity is associated with excessive erythrocytosis and chronic mountain sickness in Andean Highlanders: a review

“…These differences in Hb levels among populations in different parts of the world are correlated with the prevalence of CMS. In fact, CMS is common in Andeans, found occasionally in Tibetans and almost absent in the Ethiopian population living on the East African high‐altitude plateau (Beall et al ., ; Xing et al ., ). For such reason, a genetic basis of adaptation to high altitudes and the presence of chronic mountain sickness has been suggested (Zhou et al ., ).…”