TY - JOUR
T1 - Natural selection of immune and metabolic genes associated with health in two lowland Bolivian populations
AU - Lea, Amanda J.
AU - Garcia, Angela
AU - Arevalo, Jesusa
AU - Ayroles, Julien F.
AU - Buetow, Kenneth
AU - Cole, Steve W.
AU - Rodriguez, Daniel Eid
AU - Gutierrez, Maguin
AU - Highland, Heather M.
AU - Hooper, Paul L.
AU - Justice, Anne
AU - Kraft, Thomas
AU - North, Kari E.
AU - Stieglitz, Jonathan
AU - Kaplan, Hillard
AU - Trumble, Benjamin C.
AU - Gurven, Michael D.
N1 - Funding Information:
Data, Materials, and Software Availability. Individual-level data are stored in the Tsimane Health and Life History Project (THLHP) Data Repository, and are available throughrestrictedaccessforethicalreasons.THLHP'shighestpriorityisthesafeguard-ing of human subjects and minimization of risk to study participants. The THLHP adheres to the “CARE Principles for Indigenous Data Governance” (Collective Benefit, Authority to Control, Responsibility, and Ethics), which assure that the Tsimane and Moseten 1) have sovereignty over how data are shared, 2) are the primary gatekeepers determining ethical use, 3) are actively engaged in the data generation, and 4) derive benefit from data generated and shared for use whenever possible. The THLHP is also committed to the “FAIR Guiding Principles for scientific data management and stewardship” (Findable,Accessible,Interoperable,Reusable).Requests for individual-level data should take the form of an application that details the exact uses of the data and the research questions to be addressed, procedures that will be employed for data security and individual privacy,potential benefits to the study communities,and procedures for assessing and minimizing stigmatizing interpretations of the research results (see the following webpage for links to the data sharing policy and data request forms: https://tsimane.anth.ucsb.edu/data.html). Requests for individual-level data will require institutional IRB approval (even if exempt) and will be reviewed by an Advisory Council composed of Tsimane community leaders, community members,Bolivian scientists,and the THLHP leadership.Asimilar structure exists for the Moseten data. The study authors and the THLHP leadership are committed to open science and are available to assist interested investigators in preparing data access requests. ACKNOWLEDGMENTS. We thank Tsimane and Moseten participants and their communities, and the Tsimane Health and Life History Project field team (including San Borja office staff, physicians, biochemists, and anthropologists), whose support, expertise, and commitment made this work possible. We also thank the National Institutes of Health for their support of the Tsimane Health and Life History Project, namely awards R01AG024119, R56AG024119, and RF1AG054442.JS acknowledges IASTfunding from the French National Research Agency under the Investments for the Future (Investissements d’Avenir) program, grant ANR-17-EURE-0010.
Publisher Copyright:
© 2022 the Author(s).
PY - 2023/1/3
Y1 - 2023/1/3
N2 - A growing body of work has addressed human adaptations to diverse environments using genomic data, but few studies have connected putatively selected alleles to phenotypes, much less among underrepresented populations such as Amerindians. Studies of natural selection and genotype-phenotype relationships in underrepresented populations hold potential to uncover previously undescribed loci underlying evolutionarily and biomedically relevant traits. Here, we worked with the Tsimane and the Moseten, two Amerindian populations inhabiting the Bolivian lowlands. We focused most intensively on the Tsimane, because long-term anthropological work with this group has shown that they have a high burden of both macro and microparasites, as well as minimal cardiometabolic disease or dementia. We therefore generated genome-wide genotype data for Tsimane individuals to study natural selection, and paired this with blood mRNA-seq as well as cardiometabolic and immune biomarker data generated from a larger sample that included both populations. In the Tsimane, we identified 21 regions that are candidates for selective sweeps, as well as 5 immune traits that show evidence for polygenic selection (e.g., C-reactive protein levels and the response to coronaviruses). Genes overlapping candidate regions were strongly enriched for known involvement in immune-related traits, such as abundance of lymphocytes and eosinophils. Importantly, we were also able to draw on extensive phenotype information for the Tsimane and Moseten and link five regions (containing PSD4, MUC21 and MUC22, TOX2, ANXA6, and ABCA1) with biomarkers of immune and metabolic function. Together, our work highlights the utility of pairing evolutionary analyses with anthropological and biomedical data to gain insight into the genetic basis of health-related traits.
AB - A growing body of work has addressed human adaptations to diverse environments using genomic data, but few studies have connected putatively selected alleles to phenotypes, much less among underrepresented populations such as Amerindians. Studies of natural selection and genotype-phenotype relationships in underrepresented populations hold potential to uncover previously undescribed loci underlying evolutionarily and biomedically relevant traits. Here, we worked with the Tsimane and the Moseten, two Amerindian populations inhabiting the Bolivian lowlands. We focused most intensively on the Tsimane, because long-term anthropological work with this group has shown that they have a high burden of both macro and microparasites, as well as minimal cardiometabolic disease or dementia. We therefore generated genome-wide genotype data for Tsimane individuals to study natural selection, and paired this with blood mRNA-seq as well as cardiometabolic and immune biomarker data generated from a larger sample that included both populations. In the Tsimane, we identified 21 regions that are candidates for selective sweeps, as well as 5 immune traits that show evidence for polygenic selection (e.g., C-reactive protein levels and the response to coronaviruses). Genes overlapping candidate regions were strongly enriched for known involvement in immune-related traits, such as abundance of lymphocytes and eosinophils. Importantly, we were also able to draw on extensive phenotype information for the Tsimane and Moseten and link five regions (containing PSD4, MUC21 and MUC22, TOX2, ANXA6, and ABCA1) with biomarkers of immune and metabolic function. Together, our work highlights the utility of pairing evolutionary analyses with anthropological and biomedical data to gain insight into the genetic basis of health-related traits.
KW - Tsimane
KW - evolution
KW - genotype-phenotype
KW - health
KW - natural selection
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U2 - 10.1073/pnas.2207544120
DO - 10.1073/pnas.2207544120
M3 - Article
C2 - 36574663
AN - SCOPUS:85144810813
SN - 0027-8424
VL - 120
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
M1 - e2207544120
ER -