High-altitude Taxa Research Articles

Influence of hemoglobin-O2 affnity on aerobic capacity in deer mice

High-altitude hypoxia can constrain tissue O2 supply, and several high-altitude populations and species have evolved adaptations to overcome this challenge. Evolved increases in hemoglobin-O2 (Hb-O2) affnity are pervasive across high-altitude taxa, but the influence of such increases on aerobic capacity (maximal O2 consumption) in hypoxia remains contentious. The influence of Hb-O2 affnity on aerobic capacity in hypoxia could vary depending on other traits in the O2 transport pathway, but this possibility is poorly understood. We examined this issue in deer mice ( Peromyscus maniculatus), which is found from sea level to >4300m altitude in the Rocky Mountains. Mice from populations native to high altitude and low altitude were born and raised to adulthood in captivity. Low-altitude mice (n=14) were acclimated to warm (25°C) normoxia, and high-altitude mice (n=14) were acclimated to cold (5°C) hypoxia (~12 kPa O2) for 6 weeks, creating two groups with very different capacities for O2 transport in hypoxia. Aerobic capacity for thermogenesis (VO2max) was then measured in hypoxia after each of three pharmacological treatments to manipulate Hb-O2 affnity: saline (control); efaproxiral, a negative allosteric regulator that decreases Hb-O2 affnity; and sodium cyanate, which covalently modifies Hb and increases Hb-O2 affnity. In control conditions, high-altitude mice had higher VO2max and arterial O2 saturation (SaO2) in hypoxia and higher Hb-O2 affnity (lower P50) than low-altitude mice. Efaproxiral reduced SaO2 and led to similar decreases in VO2max in both populations. Sodium cyanate increased SaO2 in hypoxia in both populations. However, this was only associated with an increase in VO2max in 7 of 14 high-altitude mice and 4 of 14 low-altitude mice. Our results suggest that Hb-O2 affnity may be optimal for aerobic capacity in hypoxia in high-altitude mice, and that reductions in Hb-O2 affnity reduce performance. Supported by NSERC of Canada. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Genetic variation in HIF-2α attenuates ventilatory sensitivity and carotid body growth in chronic hypoxia in high-altitude deer mice.

The gene encoding HIF-2α, Epas1, has experienced a history of natural selection in many high-altitude taxa, but the functional role of mutations in this gene is still poorly understood. We investigated the influence of the high-altitude variant of Epas1 in North American deer mice (Peromyscus maniculatus) on the control of breathing and carotid body growth during chronic hypoxia. We created hybrids between high- and low-altitude populations of deer mice to disrupt linkages between genetic loci so that the physiological effects of Epas1 alleles (Epas1H and Epas1L , respectively) could be examined on an admixed genomic background. In general, chronic hypoxia (4weeks at 12kPa O2 ) enhanced ventilatory chemosensitivity (assessed as the acute ventilatory response to hypoxia), increased total ventilation and arterial O2 saturation during progressive poikilocapnic hypoxia, and increased haematocrit and blood haemoglobin content across genotypes. However, the effects of chronic hypoxia on ventilatory chemosensitivity were attenuated in mice that were homozygous for the high-altitude Epas1 allele (Epas1H/H ). Carotid body growth and glomus cell hyperplasia, which was strongly induced in Epas1L/L mice in chronic hypoxia, was not observed in Epas1H/H mice. Epas1 genotype also modulated the effects of chronic hypoxia on metabolism and body temperature depression in hypoxia, but had no effects on haematological traits. These findings confirm the important role of HIF-2α in modulating ventilatory sensitivity and carotid body growth in chronic hypoxia, and show that genetic variation in Epas1 is responsible for evolved changes in the control of breathing and metabolism in high-altitude deer mice. KEY POINTS: High-altitude natives of many species have experienced natural selection on the gene encoding HIF-2α, Epas1, including high-altitude populations of deer mice. HIF-2α regulates ventilation and carotid body growth in hypoxia, and so the genetic variants in Epas1 in high-altitude natives may underlie evolved changes in control of breathing. Deer mice from controlled crosses between high- and low-altitude populations were used to examine the effects of Epas1 genotype on an admixed genomic background. The high-altitude variant was associated with reduced ventilatory chemosensitivity and carotid body growth in chronic hypoxia, but had no effects on haematology. The results help us better understand the genetic basis for the unique physiological phenotype of high-altitude natives.

A Re-Assessment of Positive Selection on Mitochondrial Genomes of High-Elevation Phrynocephalus Lizards.

Due to their integral roles in oxidative phosphorylation, mitochondrially encoded proteins represent common targets of selection in response to altitudinal hypoxia across high-altitude taxa. While previous studies revealed evidence of positive selection on mitochondrial genomes of high-altitude Phrynocephalus lizards, their conclusions were restricted by out-of-date phylogenies and limited taxonomic sampling. Using topologies derived from both nuclear and mitochondrial DNA phylogenies, we re-assessed the evidence of positive selection on the mitochondrial genomes of high-altitude Phrynocephalus. We sampled representative species from all four main lineages and sequenced the mitochondrial genome of P. maculatus, a putative sister taxon to the high-altitude group. Positive selection was assessed through two widely used branch-site tests: the branch-site model in PAML and BUSTED in HyPhy. No evidence of positive selection on mitochondrial genes was detected on branches leading to two most recent common ancestors of high-altitude species; however, we recovered evidence of positive selection on COX1 on the P. forsythii branch, which represents a reversal from high- to low-elevation environments. A positively selected site therein marked a threonine to valine substitution at position 419. We suggest this bout of selection occurred as the ancestors of P. forsythii re-colonized lower altitude environments north of the Tibetan Plateau. Despite their role in oxidative phosphorylation, we posit that mitochondrial genes are unlikely to have represented historical targets of selection for high-altitude adaptation in Phrynocephalus. Consequently, future studies should address the roles of nuclear genes and differential gene expression.

Cardiovascular responses to progressive hypoxia in ducks native to high altitude in the Andes.

The cardiovascular system is critical for delivering O2 to tissues. Here we examine the cardiovascular responses to progressive hypoxia in four high-altitude Andean duck species compared to four related low-altitude populations in North America, tested at their native altitude. Ducks were exposed to stepwise decreases in inspired partial pressure of O2 while we monitored heart rate, O2 consumption rate, blood O2 saturation, haematocrit (Hct), and blood haemoglobin concentration [Hb]. We calculated O2 pulse (the product of stroke volume and the arterial-venous O2 content difference), blood O2 concentration, and heart rate variability. Regardless of altitude, all eight populations maintained O2 consumption rate with minimal change in heart rate or O2 pulse, indicating that O2 consumption was maintained by either a constant arterial-venous O2 content difference (an increase in the relative O2 extracted from arterial blood) or by a combination of changes in stroke volume and the arterial-venous O2 content difference. Three high-altitude taxa (yellow-billed pintails, cinnamon teal, and speckled teal) had higher Hct and [Hb], increasing the O2 content of arterial blood, and potentially providing a greater reserve for enhancing O2 delivery during hypoxia. Hct and [Hb] between low- and high-altitude populations of ruddy duck were similar, representing a potential adaptation to diving life. Heart rate variability was generally lower in high-altitude ducks, concurrent with similar or lower heart rates than low-altitude ducks, suggesting a reduction in vagal and sympathetic tone. These unique features of the Andean ducks differ from previous observations in both Andean geese and bar-headed geese, neither of which exhibit significant elevations in Hct or [Hb] compared to their low-altitude relatives, revealing yet another avian strategy for coping with high altitude.

The nature of the biological material and the irreproducibility problem in biomedical research.

Biomedical research has a reproducibility problem since various crucial landmark papers could not be independently reproduced. While there are many causes related to statistical analysis, methodology or insufficient reporting of experimental details, this commentary argues that the complexity of biological material itself is, until now, a largely ignored source of irreproducibility. By discussing examples from evolutionary biology, intrinsically disordered proteins and current biomedical research, it contends that some results are irreproducible because we do not have the knowledge, the tools or the analytical ability to understand biological complexity and how it can give rise to different results. Instead of casting irreproducible research out as bad or sloppy science, they should serve as an inspiration for pioneering research not just to develop such tools but also to attempt to explore what lies beneath our current inability to deal with complexity.

Evolved Mechanisms of Aerobic Performance and Hypoxia Resistance in High-Altitude Natives.

Comparative physiology studies of high-altitude species provide an exceptional opportunity to understand naturally evolved mechanisms of hypoxia resistance. Aerobic capacity (VO2max) is a critical performance trait under positive selection in some high-altitude taxa, and several high-altitude natives have evolved to resist the depressive effects of hypoxia on VO2max. This is associated with enhanced flux capacity through the O2 transport cascade and attenuation of the maladaptive responses to chronic hypoxia that can impair O2 transport. Some highlanders exhibit elevated rates of carbohydrate oxidation during exercise, taking advantage of its high ATP yield per mole of O2. Certain highland native animals have also evolved more oxidative muscles and can sustain high rates of lipid oxidation to support thermogenesis. The underlying mechanisms include regulatory adjustments of metabolic pathways and to gene expression networks. Therefore, the evolution of hypoxia resistance in high-altitude natives involves integrated functional changes in the pathways for O2 and substrate delivery and utilization by mitochondria.

Predictable convergence in hemoglobin function has unpredictable molecular underpinnings.

To investigate the predictability of genetic adaptation, we examined the molecular basis of convergence in hemoglobin function in comparisons involving 56 avian taxa that have contrasting altitudinal range limits. Convergent increases in hemoglobin-oxygen affinity were pervasive among high-altitude taxa, but few such changes were attributable to parallel amino acid substitutions at key residues. Thus, predictable changes in biochemical phenotype do not have a predictable molecular basis. Experiments involving resurrected ancestral proteins revealed that historical substitutions have context-dependent effects, indicating that possible adaptive solutions are contingent on prior history. Mutations that produce an adaptive change in one species may represent precluded possibilities in other species because of differences in genetic background.

The phylogeography of an alpine leaf beetle: Divergence within Oreinaelongata spans several ice ages

The genetic landscape of the European flora and fauna was shaped by the ebb and flow of populations with the shifting ice during Quaternary climate cycles. While this has been well demonstrated for lowland species, less is known about high altitude taxa. Here we analyze the phylogeography of the leaf beetle Oreina elongata from 20 populations across the Alps and Apennines. Three mitochondrial and one nuclear region were sequenced in 64 individuals. Within an mtDNA phylogeny, three of seven subspecies are monophyletic. The species is chemically defended and aposematic, with green and blue forms showing geographic variation and unexpected within-population polymorphism. These warning colors show pronounced east–west geographical structure in distribution, but the phylogeography suggests repeated origin and loss. Basal clades come from the central Alps. Ancestors of other clades probably survived across northern Italy and the northern Adriatic, before separation of eastern, southern and western populations and rapid spread through the western Alps. After reviewing calibrated gene-specific substitution rates in the literature, we use partitioned Bayesian coalescent analysis to date our phylogeography. The major clades diverged long before the last glacial maximum, suggesting that O. elongata persisted many glacial cycles within or at the edges of the Alps and Apennines. When analyzing additional barcoding pairwise distances, we find strong evidence to consider O. elongata as a species complex rather than a single species.

Vulnerable taxa of European Plecoptera (Insecta) in the context of climate change

We evaluated 516 species and/or subspecies of European stoneflies for vulnerability to climate change according to autoecological data. The variables considered were stream zonation preference, altitude preference, current preference, temperature range preference, endemism and rare species. Presence in ecoregions was used to analyse the vulnerability of taxa in relation to their distribution. We selected the variables that provided information on vulnerability to change in climate. Thus, we chose strictly crenal taxa, high-altitude taxa, rheobionts, cold stenotherm taxa, micro-endemic taxa and rare taxa. Our analysis showed that at least 324 taxa (62.79%) can be included in one or more categories of vulnerability to climate change. Of these, 43 taxa would be included in three or more vulnerability categories, representing the most threatened taxa. The most threatened species and the main factors affecting their distribution are discussed. Endangered potamal species, with populations that have decreased mainly as a consequence of habitat alteration, also could suffer from the effects of climate change. Thus, the total number of taxa at risk is particularly high. Not only are a great diversity of European stoneflies concentrated in the Alps, Pyrenees and Iberian Peninsula, but so are the most vulnerable taxa. These places are likely to be greatly affected by climate change according to climate models. In general, an impoverishment of European Plecoptera taxa will probably occur as a consequence of climate change, and only taxa with wide tolerance ranges will increase in abundance, resulting in lower overall faunal diversity.

Modern pollen deposition in the tropical lowlands of northeast Queensland, Australia

Surface sediments of mangrove, freshwater wetland and rainforest sites in northeast Queensland were sampled to obtain pollen signatures from a range of climatic and vegetational settings as a basis for interpretation of fossil pollen diagrams. Maximum terrestrial pollen diversity was predicted by curve fitting using the Putter No. 1 growth curve. Taxonomic diversity was found to be a better indicator of rainfall zone than the presence of absence of any one taxon. However, the presence of Chenopodiaceae pollen and a general lack of rainforest pollen types are characteristic of low-rainfall environments. High values for pteridophytes indicate fluvial conditions, while high-altitude taxa were found in lowland sites fed by streams draining upland vegetation. Local habitat indicators provide good evidence for the type of depositional environment, in keeping with other published studies.