Biochemical pedomorphosis and genetic assimilation in the hypoxia adaptation of Tibetan antelope

Signore, Anthony V.; Storz, Jay F.

doi:10.1126/sciadv.abb5447

Cited by 35 publications

(26 citation statements)

References 48 publications

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“…2018 ; Signore et al. 2019 ; Signore and Storz 2020 ). In some cases, in vitro experiments that quantified the phenotypic effects of specific mutations have been integrated with population genetic analyses to test for corroborative evidence that the variants in question increased in frequency under the influence of positive selection ( Storz and Kelly 2008 ; Storz et al.…”

Section: Genetic Experiments Provide Insights Into Mechanism and Procmentioning

confidence: 99%

High-Altitude Adaptation: Mechanistic Insights from Integrated Genomics and Physiology

Storz

2021

Molecular Biology and Evolution

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Population genomic analyses of high-altitude humans and other vertebrates have identified numerous candidate genes for hypoxia adaptation, and the physiological pathways implicated by such analyses suggest testable hypotheses about underlying mechanisms. Studies of highland natives that integrate genomic data with experimental measures of physiological performance capacities and subordinate traits are revealing associations between genotypes (e.g., hypoxia-inducible factor [HIF] gene variants) and hypoxia-responsive phenotypes. The subsequent search for causal mechanisms is complicated by the fact that observed genotypic associations with hypoxia-induced phenotypes may reflect second-order consequences of selection-mediated changes in other (unmeasured) traits that are coupled with the focal trait via feedback regulation. Manipulative experiments to decipher circuits of feedback control and patterns of phenotypic integration can help identify causal relationships that underlie observed genotype-phenotype associations. Such experiments are critical for correct inferences about phenotypic targets of selection and mechanisms of adaptation.

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Section: Genetic Experiments Provide Insights Into Mechanism and Procmentioning

confidence: 99%

High-Altitude Adaptation: Mechanistic Insights from Integrated Genomics and Physiology

Storz

2021

Molecular Biology and Evolution

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“…Globin gene sequencing was performed as described previously ( 40 ). In brief, RNA was extracted from ∼100 µL of flash frozen erythrocytes using the Qiagen RNeasy Universal Plus Mini Kit.…”

Section: Methodsmentioning

confidence: 99%

“…S2 ). Sequences were aligned using MUSCLE ( 42 ) and then used to estimate phylogenetic trees as described previously ( 40 ). In brief, the best-fitting codon substitution model and initial tree search were estimated using IQ-TREE with the options -st CODON, -m TESTNEW, -allnni, and -bnni ( 43 , 44 ).…”

Section: Methodsmentioning

confidence: 99%

Evolved increases in hemoglobin-oxygen affinity and the Bohr effect coincided with the aquatic specialization of penguins

Signore

Tift

Hoffmann

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Dive capacities of air-breathing vertebrates are dictated by onboard O2 stores, suggesting that physiologic specialization of diving birds such as penguins may have involved adaptive changes in convective O2 transport. It has been hypothesized that increased hemoglobin (Hb)-O2 affinity improves pulmonary O2 extraction and enhances the capacity for breath-hold diving. To investigate evolved changes in Hb function associated with the aquatic specialization of penguins, we integrated comparative measurements of whole-blood and purified native Hb with protein engineering experiments based on site-directed mutagenesis. We reconstructed and resurrected ancestral Hb representing the common ancestor of penguins and the more ancient ancestor shared by penguins and their closest nondiving relatives (order Procellariiformes, which includes albatrosses, shearwaters, petrels, and storm petrels). These two ancestors bracket the phylogenetic interval in which penguin-specific changes in Hb function would have evolved. The experiments revealed that penguins evolved a derived increase in Hb-O2 affinity and a greatly augmented Bohr effect (i.e., reduced Hb-O2 affinity at low pH). Although an increased Hb-O2 affinity reduces the gradient for O2 diffusion from systemic capillaries to metabolizing cells, this can be compensated by a concomitant enhancement of the Bohr effect, thereby promoting O2 unloading in acidified tissues. We suggest that the evolved increase in Hb-O2 affinity in combination with the augmented Bohr effect maximizes both O2 extraction from the lungs and O2 unloading from the blood, allowing penguins to fully utilize their onboard O2 stores and maximize underwater foraging time.

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“…Under conditions of severe hypoxia, an increased Hb-O 2 affinity can help safeguard arterial O 2 saturation, thereby minimizing the inevitable reduction in tissue O 2 delivery (Storz, 2016b(Storz, , 2019. Evolved increases in Hb-O 2 affinity and-in some cases-associated increases in arterial O 2 saturation in hypoxia, have been documented in several highly aerobic mammals that are native to high altitude (Storz et al, 2010a;Tate et al, 2017;Ivy et al, 2020;Signore and Storz, 2020). In the case of Tibetan mastiff Hb, a clear hypothesis is that the introgressed, wolf-derived HBB/D variants are adaptive at high altitude because they confer an increased Hb-O 2 affinity.…”

Section: β-Globin In Tibetan Canidsmentioning

confidence: 99%

Introgressive Hybridization and Hypoxia Adaptation in High-Altitude Vertebrates

Storz

Signore

2021

Front. Genet.

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In natural populations of animals, a growing body of evidence suggests that introgressive hybridization may often serve as an important source of adaptive genetic variation. Population genomic studies of high-altitude vertebrates have provided strong evidence of positive selection on introgressed allelic variants, typically involving a long-term highland species as the donor and a more recently arrived colonizing species as the recipient. In high-altitude humans and canids from the Tibetan Plateau, case studies of adaptive introgression involving the HIF transcription factor, EPAS1, have provided insights into complex histories of ancient introgression, including examples of admixture from now-extinct source populations. In Tibetan canids and Andean waterfowl, directed mutagenesis experiments involving introgressed hemoglobin variants successfully identified causative amino acid mutations and characterized their phenotypic effects, thereby providing insights into the functional properties of selectively introgressed alleles. We review case studies of adaptive introgression in high-altitude vertebrates and we highlight findings that may be of general significance for understanding mechanisms of environmental adaptation involving different sources of genetic variation.

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Biochemical pedomorphosis and genetic assimilation in the hypoxia adaptation of Tibetan antelope

Cited by 35 publications

References 48 publications

High-Altitude Adaptation: Mechanistic Insights from Integrated Genomics and Physiology

High-Altitude Adaptation: Mechanistic Insights from Integrated Genomics and Physiology

Evolved increases in hemoglobin-oxygen affinity and the Bohr effect coincided with the aquatic specialization of penguins

Introgressive Hybridization and Hypoxia Adaptation in High-Altitude Vertebrates

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