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Genomic signatures of high-altitude adaptation and chromosomal polymorphism in geladas

Nature Ecology & Evolution volume 6, pages 630–643 (2022)Cite this article

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Abstract

Primates have adapted to numerous environments and lifestyles but very few species are native to high elevations. Here we investigated high-altitude adaptations in the gelada (Theropithecus gelada), a monkey endemic to the Ethiopian Plateau. We examined genome-wide variation in conjunction with measurements of haematological and morphological traits. Our new gelada reference genome is highly intact and assembled at chromosome-length levels. Unexpectedly, we identified a chromosomal polymorphism in geladas that could potentially contribute to reproductive barriers between populations. Compared with baboons at low altitude, we found that high-altitude geladas exhibit significantly expanded chest circumferences, potentially allowing for greater lung surface area for increased oxygen diffusion. We identified gelada-specific amino acid substitutions in the alpha-chain subunit of adult haemoglobin but found that gelada haemoglobin does not exhibit markedly altered oxygenation properties compared with lowland primates. We also found that geladas at high altitude do not exhibit elevated blood haemoglobin concentrations, in contrast to the normal acclimatization response to hypoxia in lowland primates. The absence of altitude-related polycythaemia suggests that geladas are able to sustain adequate tissue-oxygen delivery despite environmental hypoxia. Finally, we identified numerous genes and genomic regions exhibiting accelerated rates of evolution, as well as gene families exhibiting expansions in the gelada lineage, potentially reflecting altitude-related selection. Our findings lend insight into putative mechanisms of high-altitude adaptation while suggesting promising avenues for functional hypoxia research.

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Fig. 1: The gelada at high altitude.
Fig. 2: Unique karyotypic evolution in geladas.
Fig. 3: Historical demography and genomic diversity among gelada populations.
Fig. 4: Gelada blood and lung phenotypes at high altitude.

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Data availability

All genomic data, including the Tgel 1.0 assembly (GenBank accession number GCA_003255815.1) and short-read sequencing data, are available through NCBI repositories and are linked to BioProject accession number PRJNA470999. Gelada haematological and morphological data are available on Dryad (https://doi.org/10.5061/dryad.fbg79cnvq). All requests for biological material from the Simien Mountains used for this manuscript will be considered and granted depending on availability. For other biological materials, requests should be made to the contributors of those materials, which are specified in the manuscript.

Code availability

All code written for this project is available on GitHub (https://github.com/smacklab/gelada-genome).

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Acknowledgements

We thank those who made this research possible, particularly the research staff (E. Jejaw, A. Fenta, S. Girmay, D. Bewket and A. Adwana), logistical support staff (T. W. Aregay and S. Asrat) and assistants and students of the Simien Mountains Gelada Research Project—especially J. Jarvey and M. Gomery—as well as the EWCA for permission and support to work in the Simien Mountains National Park. We also thank the EWCA, the Amhara Regional Government and Mehal Meda Woreda for permission to conduct research at Guassa Community Conservation Area, and B. Muluyee, N. Subsebey, B. Tessema, T. Wudimagegn and many field assistants for important logistical research support there; D. McDonald and the Cellular Imaging Core at the Fred Hutchinson Cancer Research Center for assistance with karyotyping; S. Sams and S. Ford for assistance with laboratory work; and M. Montague, K. Harris, A. Bigham, G. Scott, I. Liachko, Z. Kronenberg, O. Dudchenko, N. Simons, N. Ting and J. Dutheil for feedback through various stages of this research. Support for this research was provided by the National Science Foundation (grant nos. BCS 2010309, BCS 1848900, BCS 2013888 and BCS 1723237 to N.S.-M., BCS 1723228 to A. Lu, BCS 0715179 to T.J.B., OIA 1736249 and IOS 2114465 to J.F.S., IOS 1255974 and IOS 1854359 to J.C.B.), the National Institutes of Health (grant nos. NIA R00AG051764 to N.S.-M. and NHLBI R01HL087216 to J.F.S.), the University of Washington Royalty Research Fund, the San Diego Zoo and the German Research Foundation (grant no. DFG KN1097/3-1 to S.K.). K.L.C. was supported by a National Institutes of Health fellowship (NIA T32AG000057). M.C.J. was supported by the Natural Environment Research Council (NE/T000341/1) and the Natural Sciences and Engineering Research Council Discovery Accelerator Grant. I.A.S.-C. was supported by the ASU Center for Evolution and Medicine.

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Authors and Affiliations

  1. Center for Evolution and Medicine, Arizona State University, Tempe, AZ, USA

    Kenneth L. Chiou, India A. Schneider-Crease & Noah Snyder-Mackler

  2. School of Life Sciences, Arizona State University, Tempe, AZ, USA

    Kenneth L. Chiou, India A. Schneider-Crease & Noah Snyder-Mackler

  3. Department of Psychology, University of Washington, Seattle, WA, USA

    Kenneth L. Chiou, India A. Schneider-Crease & Noah Snyder-Mackler

  4. Nathan Shock Center of Excellence in the Basic Biology of Aging, University of Washington, Seattle, WA, USA

    Kenneth L. Chiou & Noah Snyder-Mackler

  5. Department of Anthropology and Archaeology, University of Calgary, Calgary, Alberta, Canada

    Mareike C. Janiak & Amanda D. Melin

  6. School of Science, Engineering, and Environment, University of Salford, Salford, UK

    Mareike C. Janiak

  7. Department of Anthropology, University of Michigan, Ann Arbor, MI, USA

    Sharmi Sen & Jacinta C. Beehner

  8. College of Veterinary Medicine and Agriculture, Addis Ababa University, Debre Zeit, Ethiopia

    Ferehiwot Ayele & Alemayehu Lemma

  9. Veterinary Unit, Conservation Science Department, Tanzania National Parks (TANAPA), Arusha, Tanzania

    Idrissa S. Chuma

  10. Work Group Neglected Tropical Diseases, Infection Biology Unit, German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany

    Sascha Knauf

  11. Institute for International Animal Health/One Health, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald, Germany

    Sascha Knauf

  12. School of Biological Sciences, University of Nebraska, Lincoln, NE, USA

    Anthony V. Signore & Jay F. Storz

  13. University Program in Genetics and Genomics, Duke University, Durham, NC, USA

    Anthony M. D’Ippolito

  14. Center for Genomic and Computational Biology, Duke University, Durham, NC, USA

    Anthony M. D’Ippolito

  15. African Wildlife Foundation, Debark, Ethiopia

    Belayneh Abebe

  16. Ethiopian Wildlife Conservation Authority, Addis Ababa, Ethiopia

    Abebaw Azanaw Haile & Fanuel Kebede

  17. Department of Anthropology and Environmental Studies Program, California State University Fullerton, Fullerton, CA, USA

    Peter J. Fashing & Nga Nguyen

  18. Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, Oslo, Norway

    Peter J. Fashing & Nga Nguyen

  19. Department of Mammals, Bronx Zoo, Wildlife Conservation Society, New York, NY, USA

    Colleen McCann

  20. New York Consortium in Evolutionary Primatology, New York, NY, USA

    Colleen McCann & Clifford J. Jolly

  21. Beckman Center for Conservation Research, San Diego Zoo Wildlife Alliance, Escondido, CA, USA

    Marlys L. Houck

  22. Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA

    Jeffrey D. Wall

  23. Department of Anthropology, New York University, New York, NY, USA

    Andrew S. Burrell & Clifford J. Jolly

  24. Department of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, USA

    Christina M. Bergey

  25. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA

    Jeffrey Rogers

  26. Department of Neuroscience, Washington University School of Medicine, St Louis, MO, USA

    Jane E. Phillips-Conroy

  27. Department of Anthropology, Washington University, St Louis, MO, USA

    Jane E. Phillips-Conroy

  28. Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada

    Amanda D. Melin

  29. Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada

    Amanda D. Melin

  30. Department of Anthropology, Stony Brook University, Stony Brook, NY, USA

    Amy Lu

  31. Department of Psychology, University of Michigan, Ann Arbor, MI, USA

    Jacinta C. Beehner & Thore J. Bergman

  32. Department of Ecology and Evolution, University of Michigan, Ann Arbor, MI, USA

    Thore J. Bergman

  33. Center for Studies in Demography and Ecology, University of Washington, Seattle, WA, USA

    Noah Snyder-Mackler

  34. School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, USA

    Noah Snyder-Mackler

  35. ASU-Banner Neurodegenerative Disease Research Center, Arizona State University, Tempe, AZ, USA

    Noah Snyder-Mackler

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  1. Kenneth L. Chiou
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  2. Mareike C. Janiak
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Contributions

N.S.-M., K.L.C. and M.C.J. conceived the research. K.L.C., M.C.J., I.A.S.-C., A.D.M., A. Lu, J.C.B., T.J.B. and N.S.-M. designed the study. K.L.C., I.A.S.-C., S.S., F.A., I.S.C., S.K., A. Lemma, B.A., J.C.B., T.J.B. and N.S.-M. collected field gelada samples and data, facilitated by A.A.H. and F.K. P.J.F., N.N., C.M., M.L.H., J.D.W., A.S.B., C.M.B., J.R., J.E.P.-C. and C.J.J. contributed samples and/or data. A.V.S. and J.F.S. designed, performed and analysed Hb–O2 affinity experiments. K.L.C., A.M.D. and N.S.-M. generated genomic data. K.L.C., M.C.J. and N.S.-M. performed genomic analyses. K.L.C., M.C.J. and N.S.-M. wrote the paper. All authors revised and approved the final manuscript.

Corresponding authors

Correspondence to Kenneth L. Chiou or Noah Snyder-Mackler.

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Nature Ecology & Evolution thanks Lucia Carbone and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 Gelada reference assembly quality and synteny.

(A) The gelada reference assembly (Tgel 1.0) compared to closely related papionin assemblies in assembly size (top) and contig N50 (bottom). (B) Synteny links between the anubis baboon (Panu 3.0) and gelada (Tgel 1.0) assemblies reveal strong collinearity between genomes. (C) BUSCO analysis of the gelada reference assembly reveals a relatively intact and complete assembly.

Extended Data Fig. 2 Provenience of captive gelada samples.

Maximum likelihood phylogenetic tree from the cytochrome b + hypervariable region I (HVI) D-loop mitochondrial region informs on the geographic origin of geladas in zoos. Individuals in our study were assigned either to gelada haplotypes determined by Zinner et al139. (h01–h61) or to new haplotypes determined in the current study (labelled in italics; Supplementary Table 1). Gelada individuals sampled from the wild were exclusively assigned to clades matching their geographic origin (northern or central). Zoo individuals were assigned to the central clade with the exception of a single haplotype shared by two zoo individuals, which was assigned to the northern clade. The two zoo individuals both have heterozygous (2n = 43) karyotypes and elevated fractions of northern genome-wide ancestry, indicating that they likely descended from a northern individual. A rhesus macaque reference sequence (GenBank accession NC_005943.1) was used to root the tree and is not shown. Bootstrap support values are shown for major nodes.

Extended Data Fig. 3 Karyotyping and a unique centric fission in gelada chromosome 7.

(A) Full karyotype of our female reference individual (DIX). (B) Example G-banded chromosome spread with 44 counted chromosomes. (C) Analysis of Hi-C libraries allows for determination of the presence/absence of a centric fission in chromosome 7 without the need for live cells, which are difficult to obtain from wild populations. Two wild central gelada individuals showed abundant contacts between the two arms of chromosome 7, indicating an intact chromosome and providing the first provenienced sampling to our knowledge of central gelada karyotypes.

Extended Data Fig. 4 Genome assemblies included in positive selection and gene family expansions analyses.

Chronogram was obtained from TimeTree53,54.

Extended Data Fig. 5 Gene family size changes in the gelada genome.

(A) Gene family expansions and contractions across the catarrhine tree. Here, expansion and contraction estimates are from CAFE and do not use the more stringent statistical thresholds used for downstream analyses. (B) Example of a significantly expanded gene family containing CENPF, which is found with five copies in geladas. (C) Example of a significantly expanded gene family containing SART1, which is found with four copies in geladas. Proteins are grouped using a neighbour-joining tree.

Extended Data Fig. 6 Robust signals of acceleration across GARs.

Per-base acceleration scores estimated with PhyloP reveal the distribution of elevated signals of acceleration across GARs. Some GARs (for example, GAR16 and GAR17) show signals of acceleration that are highly localized while other GARs (for example, GAR5, GAR14, and GAR25) show numerous changes that are more uniform across larger regions.

Extended Data Fig. 7 Synteny blocks and chromosomal rearrangements in the gelada reference assembly.

Ideogram generated using the alignment-free method implemented in SMASH reveals synteny blocks as well as chromosomal rearrangements between gelada (‘G’, Tgel 1.0) and anubis baboon (‘B’, Panu 3.0) genomes.

Extended Data Fig. 8 Comparisons of haemoglobin concentrations split by sex.

While gelada haemoglobin concentrations from zoos were only available with sexes unspecified, haemoglobin concentrations collected from the Simien Mountains (>3,000 metres above sea level) from each sex were not elevated, and in fact had lower mean values, than reference zoo gelada ranges of unknown sex40. The mean values from female and male high-altitude geladas were additionally lower, respectively, than those from female and male captive hamadryas baboons41. These results indicate that the observation that gelada haemoglobin concentrations are not elevated at high altitude is robust to sex differences in phenotype. Error bars represent the mean ± s.d.

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Supplementary Tables

Supplementary Tables 1–10.

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Chiou, K.L., Janiak, M.C., Schneider-Crease, I.A. et al. Genomic signatures of high-altitude adaptation and chromosomal polymorphism in geladas. Nat Ecol Evol 6, 630–643 (2022). https://doi.org/10.1038/s41559-022-01703-4

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