Our ancestral physiological phenotype: An adaptation for hypoxia tolerance and for endurance performance?

Abstract

There are well known mechanistic similarities in human physiology between adaptations for endurance performance and hypoxia tolerance. By using background principles arising from recent studies of the evolution of the diving response in marine mammals, here we analyze human responses to hypobaric hypoxia based on studies with several different low and high altitude human lineages. As in the evolution of the diving response in pinnipeds, we found ''conservative'' and ''adaptable'' physiological characters involved in human responses to hypoxia. Because the analysis concerns traits within a single species, conservative characters dominate the picture (they define basic human physiology and largely are independent of environmental parameters). Most notably, we also found evidence for adaptable characters forming the foundations for a fairly unique physiological phenotype-a low capacity version favored under hypobaric hypoxia and a high capacity one favored for endurance performance. Because current evidence implies that the human species arose under conditions that were getting colder, drier, and higher (situations in which these traits would have been advantageous), we hypothesize that this physiology is our ''ancestral'' condition.Numerous recent studies on origins and evolution of hominids imply that the human species arose in environments that were getting drier and higher under which endurance performance capacities and hypoxia tolerance would have been favored (1). This idea is interesting to us because biomedical researchers have long known that there are quite a few mechanistic similarities in human physiology between adaptations for endurance performance and for hypoxia tolerance (2-5). How physiological systems for hypoxia tolerance or endurance performance might have evolved within our phylogeny has remained unknown and uninvestigated in part because, until recently, there were few if any guidelines for tracing the evolutionary pathways of complex physiological systems in humans or in animals. At least, initial guidelines have arisen from recent quantitative analyses of the variability of the diving response in pinnipeds. These studies (6) led to three principles of evolution of the diving response that may be generally applicable to the evolution of complex physiological systems: (i) Some physiological͞biochemical characters considered necessary in diving animals are conserved in all pinnipeds; these traits, presumably maintained largely by negative selection (any mutations affecting them not surviving), include diving apnea, bradycardia, tissue hypoperfusion, and hypometabolism of hypoperfused tissues. At this stage in our understanding of diving physiology and biochemistry, we are unable to detect any correlation between these characters and diving capacity; (ii) a few other physiological͞biochemical characters are more malleable and are correlated with long duration diving and prolonged foraging at sea. These characters include spleen weight, blood volume, and red blood cell (RBC) mass. The l...

Maximum aerobic performance in lines ofMusselected for high wheel-running activity: effects of selection, oxygen availability and the mini-muscle phenotype

“…This interesting result seems consistent with the idea that phenotypes favorable for locomotor endurance might also evolve as a correlated response to selection for hypoxia tolerance (Hochachka et al, 1998). Further, it would seem that a selection experiment designed to increase hypoxia tolerance could be a novel way to explore such hypotheses about correlated evolution of complex phenotypes (see and references therein).…”

Long-term exposure to intermittent hypoxia results in increased hemoglobin mass, reduced plasma volume, and elevated erythropoietin plasma levels in man

“…Although there is no sharp line separating the acute and acclimatory phases of hypoxia exposure, most hypoxia response systems are unable to go to completion during acute hypoxia (Hochachka et al 1998). Prolonged exposure to hypoxia results in elevated erythropoiesis, and in some cases this causes to excessive erythrocytosis, a condition known as Monge disease (Winslow et al 1987).…”

Fine tuning the HIF‐1 ‘global’ O2 sensor for hypobaric hypoxia in Andean high‐altitude natives

“…(14) Variation in the gene encoding HIF-1a or in the genes under HIF-1 influence, could well alter an organisms physiological response to hypoxia. In our laboratory's ongoing studies of the role of genetic variants in human hypobaric hypoxia adaptations, (15)(16)(17) we reasoned that sequence modification of HIF1A (in keeping with standard human genetic nomenclature, gene symbols are in italicised capitals, e.g. EPO, HIF1A; see http://www.gene.…”