Genetic variation in haemoglobin is associated with evolved changes in breathing in high-altitude deer mice.

Physiological systems often have emergent properties but the effects of genetic variation on physiology are often unknown, which presents a major challenge to understanding the mechanisms of phenotypic evolution. We investigated whether genetic variants in haemoglobin (Hb) that contribute to high-altitude adaptation in deer mice (Peromyscus maniculatus) are associated with evolved changes in the control of breathing. We created F2 inter-population hybrids of highland and lowland deer mice to test for phenotypic associations of α- and ß-globin variants on a mixed genetic background. Hb genotype had expected effects on Hb-O2 affinity that were associated with differences in arterial O2 saturation in hypoxia. However, high-altitude genotypes were also associated with breathing phenotypes that should contribute to enhancing O2 uptake in hypoxia. Mice with highland α-globin exhibited a more effective breathing pattern, with highland homozygotes breathing deeper but less frequently across a range of inspired O2, and this difference was comparable to the evolved changes in breathing pattern in deer mouse populations native to high altitude. The ventilatory response to hypoxia was augmented in mice that were homozygous for highland ß-globin. The association of globin variants with variation in breathing phenotypes could not be recapitulated by acute manipulation of Hb-O2 affinity, because treatment with efaproxiral (a synthetic drug that acutely reduces Hb-O2 affinity) had no effect on breathing in normoxia or hypoxia. Therefore, adaptive variation in Hb may have unexpected effects on physiology in addition to the canonical function of this protein in circulatory O2 transport.

The adaptive benefit of evolved increases in hemoglobin-O2 affinity is contingent on tissue O2 diffusing capacity in high-altitude deer mice.

BACKGROUND: Complex organismal traits are often the result of multiple interacting genes and sub-organismal phenotypes, but how these interactions shape the evolutionary trajectories of adaptive traits is poorly understood. We examined how functional interactions between cardiorespiratory traits contribute to adaptive increases in the capacity for aerobic thermogenesis (maximal O2 consumption, V̇O2max, during acute cold exposure) in high-altitude deer mice (Peromyscus maniculatus). We crossed highland and lowland deer mice to produce F2 inter-population hybrids, which expressed genetically based variation in hemoglobin (Hb) O2 affinity on a mixed genetic background. We then combined physiological experiments and mathematical modeling of the O2 transport pathway to examine the links between cardiorespiratory traits and V̇O2max. RESULTS: Physiological experiments revealed that increases in Hb-O2 affinity of red blood cells improved blood oxygenation in hypoxia but were not associated with an enhancement in V̇O2max. Sensitivity analyses performed using mathematical modeling showed that the influence of Hb-O2 affinity on V̇O2max in hypoxia was contingent on the capacity for O2 diffusion in active tissues. CONCLUSIONS: These results suggest that increases in Hb-O2 affinity would only have adaptive value in hypoxic conditions if concurrent with or preceded by increases in tissue O2 diffusing capacity. In high-altitude deer mice, the adaptive benefit of increasing Hb-O2 affinity is contingent on the capacity to extract O2 from the blood, which helps resolve controversies about the general role of hemoglobin function in hypoxia tolerance.

A test of altitude-related variation in aerobic metabolism of Andean birds.

Endotherms at high altitude face the combined challenges of cold and hypoxia. Cold increases thermoregulatory costs, and hypoxia may limit both thermogenesis and aerobic exercise capacity. Consequently, in comparisons between closely related highland and lowland taxa, we might expect to observe consistent differences in basal metabolic rate (BMR), maximal metabolic rate (MMR) and aerobic scope. Broad-scale comparative studies of birds reveal no association between BMR and native elevation, and altitude effects on MMR have not been investigated. We tested for altitude-related variation in aerobic metabolism in 10 Andean passerines representing five pairs of closely related species with contrasting elevational ranges. Mass-corrected BMR and MMR were significantly higher in most highland species relative to their lowland counterparts, but there was no uniform elevational trend across all pairs of species. Our results suggest that there is no simple explanation regarding the ecological and physiological causes of elevational variation in aerobic metabolism.

An extinct hummingbird species that never was: a cautionary tale about sampling issues in molecular phylogenetics.

The selection of species and individuals for molecular analyses critically affects inferences in various fields of systematic biology including phylogenetics, phylogeography, and species delimitation. Especially in areas like the Neotropical region where molecular analyses have recovered substantial within-species divergence and unexpected affinities of populations (Turchetto-Zolet et al. 2013), biases resulting from incomplete taxonomic or geographic sampling may compromise the understanding of phylogenetic relationships (Avendaño et al. 2017). Here we describe a case in which assessments of the validity of a potentially extinct species of Neotropical bird were likely compromised because within-species variation was not accounted for in phylogenetic analyses evaluating the alternative hypothesis that the only known specimen may represent a hybrid.

Non-monophyly and deep genetic differentiation across low-elevation barriers in a Neotropical montane bird (Basileuterus tristriatus; Aves: Parulidae).

Most widespread birds of Neotropical cloud forests exhibit phenotypic variation that is partitioned geographically suggesting allopatric divergence, but little is known about the extent to which such phenotypic differentiation is consistent with genetic variation. We studied geographic patterns of genetic differentiation in the Three-striped Warbler (Basileuterus tristriatus), a polytypic and widespread understory bird of the foothills and mid-elevation zone of the tropical Andes and adjacent mountains of Central and South America. We sequenced mitochondrial DNA for 196 samples covering the entire range of B. tristriatus, as well as 22 samples of its putative closest relatives: the Three-banded (B. trifasciatus) and Santa Marta (B. basilicus) warblers. We found deep genetic structure across the range of B. tristriatus, which consisted of ten major clades including B. trifasciatus, a species that was nested within B. tristriatus. In contrast, B. basilicus was not closely related to B. tristriatus but part of a clade of Myiothlypis warblers. Geographic boundaries among clades were clearly related to lowland gaps separating subspecies groups. The subspecies melanotis of the mountains of Central America was sister to a large clade including B. t. tacarcunae, and the rest of South American clades, including B. trifasciatus. Five clades are found in the northern Andes, where no signs of gene flow were found across barriers such as the Táchira Depression or the Magdalena valley. Our study highlights the importance of valleys in promoting and maintaining divergence in a lower montane forest bird. The substantial genetic and phenotypic differentiation, and the paraphyly uncovered in B. tristriatus, may call for revising its species boundaries.

No population genetic structure in a widespread aquatic songbird from the Neotropics.

Neotropical lowland organisms often show marked population genetic structure, suggesting restricted migration among populations. However, most phylogeographic studies have focused on species inhabiting humid forest interior. Little attention has been devoted to the study of species with ecologies conducive to dispersal, such as those of more open and variable environments associated with watercourses. Using mtDNA sequences, we examined patterns of genetic variation in a widely distributed Neotropical songbird of aquatic environments, the Yellow-hooded Blackbird (Icteridae, Chrysomus icterocephalus). In contrast to many forest species, Yellow-hooded Blackbirds showed no detectable genetic structure across their range, which includes lowland populations on both sides of the Andes, much of northeastern South America, Amazonia, as well as a phenotypically distinct highland population in Colombia. A coalescent-based analysis of the species indicated that its effective population size has increased considerably, suggesting a range expansion. Our results support the hypothesis that species occurring in open habitats and tracking temporally dynamic environments should show increased dispersal propensities (hence gene flow) relative to species from closed and more stable environments. The phenotypic and behavioral variation among populations of our study species appears to have arisen recently and perhaps in the face of gene flow.