Convergent evolution in human and domesticate adaptation to high-altitude environments

Humans and their domestic animals have lived and thrived in high-altitude environments worldwide for thousands of years. These populations have developed a number of adaptations to survive in a hypoxic environment, and several genomic studies have been conducted to identify the genes that drive these adaptations. Here, we discuss the various adaptations and genetic variants that have been identified as adaptive in human and domestic animal populations and the ways in which convergent evolution has occurred as these populations have adapted to high-altitude environments. We found that human and domesticate populations have adapted to hypoxic environments in similar ways. Specific genes and biological pathways have been involved in high-altitude adaptation for multiple populations, although the specific variants differ between populations. Additionally, we found that the gene EPAS1 is often a target of selection in hypoxic environments and has been involved in multiple adaptive introgression events. High-altitude environments exert strong selective pressures, and human and animal populations have evolved in convergent ways to cope with a chronic lack of oxygen. This article is part of the theme issue ‘Convergent evolution in the genomics era: new insights and directions'.

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Widespread signals of convergent adaptation to high altitude in Asia and America

10.1101/002816 ◽

2014 ◽

Author(s):

Matthieu Foll ◽

Oscar E. Gaggiotti ◽

Josephine T. Daub ◽

Alexandra Vatsiou ◽

Laurent Excoffier

Keyword(s):

Low Power ◽

High Altitude ◽

Convergent Evolution ◽

Bayesian Method ◽

Biological Pathways ◽

Human Populations ◽

Biological Processes ◽

Genomic Studies ◽

Altitude Adaptation ◽

Hierarchical Bayesian Method

Living at high-altitude is one of the most difficult challenges that humans had to cope with during their evolution. Whereas several genomic studies have revealed some of the genetic bases of adaptations in Tibetan, Andean and Ethiopian populations, relatively little evidence of convergent evolution to altitude in different continents has accumulated. This lack of evidence can be due to truly different evolutionary responses, but it can be also due to the low power of former studies that have mainly focused on populations from a single geographical region or performed separate analyses on multiple pairs of populations to avoid problems linked to shared histories between some populations. We introduce here a hierarchical Bayesian method to detect local adaptation that can deal with complex demographic histories. Our method can identify selection occurring at different scales, as well as convergent adaptation in different regions. We apply our approach to the analysis of a large SNP dataset from low- and high-altitude human populations from America and Asia. The simultaneous analysis of these two geographic areas allows us to identify several candidate genome regions for altitudinal selection, and we show that convergent evolution among continents has been quite common. In addition to identifying several genes and biological processes involved in high altitude adaptation, we identify two specific biological pathways that could have evolved in both continents to counter toxic effects induced by hypoxia.

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Introgressive Hybridization and Hypoxia Adaptation in High-Altitude Vertebrates

Frontiers in Genetics ◽

10.3389/fgene.2021.696484 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jay F. Storz ◽

Anthony V. Signore

Keyword(s):

Genetic Variation ◽

High Altitude ◽

Case Studies ◽

Natural Populations ◽

Introgressive Hybridization ◽

The Tibetan Plateau ◽

Adaptive Genetic Variation ◽

Adaptive Introgression ◽

Genomic Studies ◽

Amino Acid Mutations

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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A Novel PHD2 Mutation Associated with Tibetan Genetic Adaptation to High Altitude Hypoxia.

Blood ◽

10.1182/blood.v116.21.2602.2602 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2602-2602 ◽

Cited By ~ 4

Author(s):

Felipe R Lorenzo V ◽

Tatum S Simonson ◽

Yingzhong Yang ◽

Rili Ge ◽

Josef T. Prchal

Keyword(s):

High Altitude ◽

Conflicts Of Interest ◽

Direct Sequencing ◽

The Body ◽

Negative Regulator ◽

Missense Mutations ◽

Genome Wide ◽

Hypoxic Environment ◽

Exon 1 ◽

Altitude Adaptation

Abstract Abstract 2602 The ability of the body to maintain oxygen hemostasis is essential for its survival. The body is required to adapt to the physiologic constraints imposed by a hypoxic environment in order to ensure optimal physiological functions. The study of indigenous high-altitude residents provides an opportunity to identify genes that may have play a role in hypoxia adaptation, and recent studies indicate that Tibetans have genetically adapted to the extremely hypoxic environment at high altitude. Interestingly, Tibetan adaption includes protection from polycythemia. We recently reported genome-wide scans of selection (Affymetrix Human SNP chips v6.0) for Tibetans (Simonson, Science July, 2010). At least 10 chromosomal regions were identified as likely targets for high-altitude adaptation, and two of these regions, EGLN1 (PHD2) and PPARA, were associated with protection against high-altitude polycythemia which is unique to this indigenous highland population. PHD2 is a negative regulator of the alpha subunits of HIF-1 and HIF-2 transcription factors regulating many essential functions including erythropoiesis, iron metabolism, development, in addition to other functions. A gain of function mutation of the alpha subunit of HIF-2 is associated with congenital polycythemia. We sequenced the exons of PPARA and PHD2 by direct sequencing and found two missense mutations in exon 1 of the PHD2 gene: the first is located within codon 4, and changes Aspartate to Glutamate (Asp4Glu) and the second is an unvalidated SNP (rs12097901) at codon 127 that changes Cysteine to Serine (Cy127Ser). The samples with high Hb show a heterozygous change, while the subject with normal Hb exhibited a homozygous change in both codons of the PHD2 gene. The association of these two missense PHD2 mutations to hemoglobin level is now being evaluated by studies of a larger population of Tibetan natives and the functional effects on levels and activities of HIF-1 and HIF-2 genes evaluated by transfection of these mutated PHD2 cDNA constructs in reporter cells. Table 1. List of samples and controls screened for mutation in PHD2. Sample Race Sex Hb PHD2 Mutation Asp4Glu Cys127Ser T03 Tibetan F 194 Hetero Hetero T43 Tibetan M 194 Hetero Hetero T48 Tibetan M 101 Hetero Homo T53 Tibetan M 159 Homo Homo Control Caucasian M ? WT WT Control Caucasian F ? WT WT Disclosure: No relevant conflicts of interest to declare.

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Physiological Genomics of Adaptation to High-Altitude Hypoxia

Annual Review of Animal Biosciences ◽

10.1146/annurev-animal-072820-102736 ◽

2020 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Jay F. Storz ◽

Zachary A. Cheviron

Keyword(s):

High Altitude ◽

Regulatory Networks ◽

Experimental Tests ◽

Lessons Learned ◽

Aerobic Performance ◽

Deer Mice ◽

Annual Review ◽

Publication Date ◽

Genomic Studies ◽

Altitude Adaptation

Population genomic studies of humans and other animals at high altitude have generated many hypotheses about the genes and pathways that may have contributed to hypoxia adaptation. Future advances require experimental tests of such hypotheses to identify causal mechanisms. Studies to date illustrate the challenge of moving from lists of candidate genes to the identification of phenotypic targets of selection, as it can be difficult to determine whether observed genotype–phenotype associations reflect causal effects or secondary consequences of changes in other traits that are linked via homeostatic regulation. Recent work on high-altitude models such as deer mice has revealed both plastic and evolved changes in respiratory, cardiovascular, and metabolic traits that contribute to aerobic performance capacity in hypoxia, and analyses of tissue-specific transcriptomes have identified changes in regulatory networks that mediate adaptive changes in physiological phenotype. Here we synthesize recent results and discuss lessons learned from studies of high-altitude adaptation that lie at the intersection of genomics and physiology. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 9 is February 16, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Faculty Opinions recommendation of The molecular basis of high-altitude adaptation in deer mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1079774.532691 ◽

2007 ◽

Author(s):

Ary Hoffmann

Keyword(s):

High Altitude ◽

Molecular Basis ◽

Deer Mice ◽

High Altitude Adaptation ◽

Altitude Adaptation

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Faculty Opinions recommendation of Evolutionary and functional insights into the mechanism underlying high-altitude adaptation of deer mouse hemoglobin.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1163704.625482 ◽

2009 ◽

Author(s):

Anthony Zera

Keyword(s):

High Altitude ◽

Deer Mouse ◽

High Altitude Adaptation ◽

Altitude Adaptation

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

Molecular Biology and Evolution ◽

10.1093/molbev/msab064 ◽

2021 ◽

Author(s):

Jay F Storz

Keyword(s):

High Altitude ◽

Hypoxia Inducible Factor ◽

Feedback Regulation ◽

Genomic Analyses ◽

Manipulative Experiments ◽

Altitude Adaptation ◽

Mechanisms Of Adaptation ◽

Physiological Pathways ◽

Underlying Mechanisms ◽

Integrated Genomics

AbstractPopulation 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 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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Whole-genome sequence data suggests environmental adaptation of Ethiopian sheep populations

Genome Biology and Evolution ◽

10.1093/gbe/evab014 ◽

2021 ◽

Author(s):

Pamela Wiener ◽

Christelle Robert ◽

Abulgasim Ahbara ◽

Mazdak Salavati ◽

Ayele Abebe ◽

...

Keyword(s):

High Altitude ◽

Environmental Variables ◽

Large Scale ◽

Sequence Data ◽

Strong Association ◽

Environmental Adaptation ◽

Whole Genome Sequence ◽

Single Nucleotide Variants ◽

High Altitude Adaptation ◽

Altitude Adaptation

Abstract Great progress has been made over recent years in the identification of selection signatures in the genomes of livestock species. This work has primarily been carried out in commercial breeds for which the dominant selection pressures, are associated with artificial selection. As agriculture and food security are likely to be strongly affected by climate change, a better understanding of environment-imposed selection on agricultural species is warranted. Ethiopia is an ideal setting to investigate environmental adaptation in livestock due to its wide variation in geo-climatic characteristics and the extensive genetic and phenotypic variation of its livestock. Here, we identified over three million single nucleotide variants across 12 Ethiopian sheep populations and applied landscape genomics approaches to investigate the association between these variants and environmental variables. Our results suggest that environmental adaptation for precipitation-related variables is stronger than that related to altitude or temperature, consistent with large-scale meta-analyses of selection pressure across species. The set of genes showing association with environmental variables was enriched for genes highly expressed in human blood and nerve tissues. There was also evidence of enrichment for genes associated with high-altitude adaptation although no strong association was identified with hypoxia-inducible-factor (HIF) genes. One of the strongest altitude-related signals was for a collagen gene, consistent with previous studies of high-altitude adaptation. Several altitude-associated genes also showed evidence of adaptation with temperature, suggesting a relationship between responses to these environmental factors. These results provide a foundation to investigate further the effects of climatic variables on small ruminant populations.

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