Evolution, Genetic Diversity, and Health

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2025 Mar 7

PMID 40055519

Authors

Maria J Palma-Martinez

Yuridia S Posadas-Garcia

Amara Shaukat

Brenda E Lopez-Angeles

Mashaal Sohail

Affiliations

Soon will be listed here.

Abstract

Human genetic diversity in today's world has been shaped by evolutionary history, demographic shifts and environmental exposures, influencing complex traits, disease susceptibility and drug responses. Capturing this diversity is essential for advancing precision medicine and promoting equitable healthcare. Despite the great progress achieved with initiatives such as the human Pangenome and large biobanks that aim for a better representation of human diversity, important challenges remain. In this Perspective, we discuss the importance of diversity in clinical genomics through an evolutionary lens. We highlight progress and challenges and outline key clinical applications of diverse genetic data. We argue that diversifying both datasets and methodologies-integrating ancestral and environmental factors-is crucial for fully understanding the genetic basis of human health and disease.

References

Benton M, Abraham A, LaBella A, Abbot P, Rokas A, Capra J . The influence of evolutionary history on human health and disease. Nat Rev Genet. 2021; 22(5):269-283. PMC: 7787134. DOI: 10.1038/s41576-020-00305-9. View

Hancock A, Witonsky D, Alkorta-Aranburu G, Beall C, Gebremedhin A, Sukernik R . Adaptations to climate-mediated selective pressures in humans. PLoS Genet. 2011; 7(4):e1001375. PMC: 3080864. DOI: 10.1371/journal.pgen.1001375. View

Huerta-Sanchez E, Jin X, Asan , Bianba Z, Peter B, Vinckenbosch N . Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA. Nature. 2014; 512(7513):194-7. PMC: 4134395. DOI: 10.1038/nature13408. View

Sohail M, Palma-Martinez M, Chong A, Quinto-Cortes C, Barberena-Jonas C, Medina-Munoz S . Mexican Biobank advances population and medical genomics of diverse ancestries. Nature. 2023; 622(7984):775-783. PMC: 10600006. DOI: 10.1038/s41586-023-06560-0. View

Malawsky D, van Walree E, Jacobs B, Heng T, Huang Q, Sabir A . Influence of autozygosity on common disease risk across the phenotypic spectrum. Cell. 2023; 186(21):4514-4527.e14. PMC: 10580289. DOI: 10.1016/j.cell.2023.08.028. View

Hussain M, Sadigh M, Sadigh M, Rastegar A, Sewankambo N . Colonization and decolonization of global health: which way forward?. Glob Health Action. 2023; 16(1):2186575. PMC: 10035955. DOI: 10.1080/16549716.2023.2186575. View

Fatumo S, Chikowore T, Choudhury A, Ayub M, Martin A, Kuchenbaecker K . A roadmap to increase diversity in genomic studies. Nat Med. 2022; 28(2):243-250. PMC: 7614889. DOI: 10.1038/s41591-021-01672-4. View

Zeberg H, Paabo S . The major genetic risk factor for severe COVID-19 is inherited from Neanderthals. Nature. 2020; 587(7835):610-612. DOI: 10.1038/s41586-020-2818-3. View

Ji A, Shaukat A, Takei R, Bixley M, Cadzow M, Topless R . Aotearoa New Zealand Māori and Pacific Population-amplified Gout Risk Variants: Is a Separate Risk Gene at the Locus. J Rheumatol. 2021; 48(11):1736-1744. DOI: 10.3899/jrheum.201684. View

10.

Petrovic J, Pesic V, Lauschke V . Frequencies of clinically important CYP2C19 and CYP2D6 alleles are graded across Europe. Eur J Hum Genet. 2019; 28(1):88-94. PMC: 6906321. DOI: 10.1038/s41431-019-0480-8. View

11.

Tishkoff S, Dietzsch E, Speed W, Pakstis A, Kidd J, Cheung K . Global patterns of linkage disequilibrium at the CD4 locus and modern human origins. Science. 1996; 271(5254):1380-7. DOI: 10.1126/science.271.5254.1380. View

12.

Simon A, Coop G . The contribution of gene flow, selection, and genetic drift to five thousand years of human allele frequency change. Proc Natl Acad Sci U S A. 2024; 121(9):e2312377121. PMC: 10907250. DOI: 10.1073/pnas.2312377121. View

13.

Alkan C, Coe B, Eichler E . Genome structural variation discovery and genotyping. Nat Rev Genet. 2011; 12(5):363-76. PMC: 4108431. DOI: 10.1038/nrg2958. View

14.

Li C, Qian Q, Yan C, Lu M, Li L, Li P . HervD Atlas: a curated knowledgebase of associations between human endogenous retroviruses and diseases. Nucleic Acids Res. 2023; 52(D1):D1315-D1326. PMC: 10767980. DOI: 10.1093/nar/gkad904. View

15.

Liao W, Asri M, Ebler J, Doerr D, Haukness M, Hickey G . A draft human pangenome reference. Nature. 2023; 617(7960):312-324. PMC: 10172123. DOI: 10.1038/s41586-023-05896-x. View

16.

Lewis A, Molina S, Appelbaum P, Dauda B, Di Rienzo A, Fuentes A . Getting genetic ancestry right for science and society. Science. 2022; 376(6590):250-252. PMC: 10135340. DOI: 10.1126/science.abm7530. View

17.

Kerner G, Quintana-Murci L . The genetic and evolutionary determinants of COVID-19 susceptibility. Eur J Hum Genet. 2022; 30(8):915-921. PMC: 9244541. DOI: 10.1038/s41431-022-01141-7. View

18.

Ceballos F, Joshi P, Clark D, Ramsay M, Wilson J . Runs of homozygosity: windows into population history and trait architecture. Nat Rev Genet. 2018; 19(4):220-234. DOI: 10.1038/nrg.2017.109. View

19.

Kirin M, Mcquillan R, Franklin C, Campbell H, McKeigue P, Wilson J . Genomic runs of homozygosity record population history and consanguinity. PLoS One. 2010; 5(11):e13996. PMC: 2981575. DOI: 10.1371/journal.pone.0013996. View

20.

Swinford N, Gallagher B, Sheehama J, Lin M, Prall S, Scelza B . Examination of runs of homozygosity in relation to height in an endogamous Namibian population. Am J Biol Anthropol. 2023; 180(1):207-215. PMC: 9937629. DOI: 10.1002/ajpa.24660. View