Population history and gene divergence in native Mexicans inferred from 76 human exomes
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Abstract
Native American genetic variation remains underrepresented in most catalogs of human genome sequencing data. Previous genotyping efforts have revealed that Mexico's Indigenous population is highly differentiated and substructured, thus potentially harboring higher proportions of private genetic variants of functional and biomedical relevance. Here we have targeted the coding fraction of the genome and characterized its full site frequency spectrum by sequencing 76 exomes from five Indigenous populations across Mexico. Using diffusion approximations, we modeled the demographic history of Indigenous populations from Mexico with northern and southern ethnic groups splitting 7.2 KYA and subsequently diverging locally 6.5 and 5.7 KYA, respectively. Selection scans for positive selection revealed BCL2L13 and KBTBD8 genes as potential candidates for adaptive evolution in Rarámuris and Triquis, respectively. BCL2L13 is highly expressed in skeletal muscle and could be related to physical endurance, a well-known phenotype of the northern Mexico Rarámuri. The KBTBD8 gene has been associated with idiopathic short stature and we found it to be highly differentiated in Triqui, a southern Indigenous group from Oaxaca whose height is extremely low compared to other Native populations.
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PBS identified alleles in multiple genes that have already been identified as targets of adaptive introgression, as well as in novel candidate genes, including some that govern development and cardiac function.
“We used PBS to identify possible candidates for adaptive introgression that were unique to admixed American populations and identified alleles in multiple genes that have already been identified as targets of adaptive introgression (Racimo et al. 2017, 2018; Ávila-Arcos et al. 2020), as well as in novel candidate genes, including some that govern development and cardiac function.”
From The Impact of Modern Admixture on Archaic Human Ancestry in Human Populations (2023) · cites this paper as Ávila-Arcos et al. 2020
The Results (Adaptive Evolution in Native Mexicans) report a PBS signal in FAP and describe it as previously suggested to be under adaptive archaic introgression; they also list candidate genes involved in differentiation and cardiac muscle contraction. The Discussion (Targets of Adaptive Evolution in NM) confirms an archaic haplotype in Native Mexicans. This source supports FAP as one example, but does not establish that multiple genes it identified were already targets of adaptive introgression. (LLM, conf=0.83)
Experimental — accuracy not yet measuredSome of the regions with high-frequency archaic alleles contain genes already identified as adaptively introgressed in Indigenous American populations, including IFIH1/FAP and WARS2 in PEL, and LRRK2/MUC19 in MXL.
“Some of these regions contain genes that have already been identified as adaptively introgressed in Indigenous American populations, including IFIH1/FAP (Ávila-Arcos et al. 2020) and WARS2 (Racimo et al. 2018), identified in PEL, and LRRK2/MUC19 (Reynolds et al. 2019), identified in MXL.”
From The Impact of Modern Admixture on Archaic Human Ancestry in Human Populations (2023) · cites this paper as Ávila-Arcos et al. 2020
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The Impact of Modern Admixture on Archaic Human Ancestry in Human Populations
Witt, K. E., Funk, A., Añorve-Garibay, V., Fang, L. L., & Huerta-Sánchez, E. (2023) · Genome Biology and Evolution · doi:10.1093/gbe/evad066 · Cited by 29 · see citing works
- Authors
- Ávila-Arcos, M. C., McManus, K. F., Sandoval, K., Rodríguez-Rodríguez, J. E., Villa-Islas, V., Martin, A. R., Luisi, P., Peñaloza-Espinosa, R. I., Eng, C., Huntsman, S., Burchard, E. G., Gignoux, C. R., Bustamante, C. D., & Moreno-Estrada, A.
- Affiliations
- International Laboratory for Human Genome Research (LIIGH), UNAM Juriquilla, Queretaro, Mexico
- Stanford Medicine (US)
- Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (MX)
- Universidad Nacional Autónoma de México (MX)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Division of Biological and Health Sciences, Department of Biological Systems, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico
- University of California, San Francisco (US)
- University of Colorado Denver (US)
- National Laboratory of Genomics for Biodiversity (LANGEBIO), UGA, CINVESTAV, Irapuato, Guanajuato 36821, Mexico
- ORCID
- Venue
- Molecular Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-12-17
- Volume
- 37
- Issue
- 4
- Pages
- 994-1006
- ISSN
- 0737-4038 (ISSN-L)
- 1537-1719
- PMC
- PMC7086176
- OpenAlex
- W2996217902
- Cited by
- 50
- References
- 79
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 10 · 2021: 13 · 2020: 7
- FWCI
- 5.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Biology and Evolution (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
- Funders
- Beijing Genomics Institute
- BGI
- Stanford Center for Computational, Evolutionary and Human Genomics
- CEHG
- Laboratorio Nacional de Visualización Científica Avanzada
- Mexico’s CONACYT Basic Research Program (CB-2015-01-251380)
- International Center for Genetic Engineering and Biotechnology (ICGEB, CRP/MEX15-04_EC)
- Health Care Research in Developing Countries
- Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica
- Universidad Nacional Autónoma de México (IA206817)
- CONACYT Infrastructure (26944)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- population structure, demographic history, site frequency spectrum, exome sequencing, positive selection, BCL2L13, Rarámuri, short stature, physical endurance, adaptive evolution
- MeSH terms
- Adaptation, Biological, Humans, Mexico, Genetic Variation, Evolution, Molecular, American Indian or Alaska Native, Phylogeography, Exome
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