The genomic landscape of Mexican Indigenous populations brings insights into the peopling of the Americas

Abstract

The genetic makeup of Indigenous populations inhabiting Mexico has been strongly influenced by geography and demographic history. Here, we perform a genome-wide analysis of 716 newly genotyped individuals from 60 of the 68 recognized ethnic groups in Mexico. We show that the genetic structure of these populations is strongly influenced by geography, and our demographic reconstructions suggest a decline in the population size of all tested populations in the last 15–30 generations. We find evidence that Aridoamerican and Mesoamerican populations diverged roughly 4–9.9 ka, around the time when sedentary farming started in Mesoamerica. Comparisons with ancient genomes indicate that the Upward Sun River 1 (USR1) individual is an outgroup to Mexican/South American Indigenous populations, whereas Anzick-1 was more closely related to Mesoamerican/South American populations than to those from Aridoamerica, showing an even more complex history of divergence than recognized so far.

Genetic Distribution of Five Spinocerebellar Ataxia Microsatellite Loci in Mexican Native American Populations and Its Impact on Contemporary Mestizo Populations

“…Departure from the HW equilibrium due to heterozygote deficiency was not an unexpected result in MNA populations, considering the fact that this phenomenon is a signature of inbreeding populations. The MNA genetic architecture seems to be influenced by geographic barriers that keep them isolated [ 21 ]. MNA populations are also deeply rooted in their traditions, maintaining thus their native language and cultural practices, despite 500 years of miscegenation [ 22 ].…”

“…MNA populations are also deeply rooted in their traditions, maintaining thus their native language and cultural practices, despite 500 years of miscegenation [ 22 ]. Both features have favored the contemporary Natives to maintain their ancestral connections and to settle down in geographic areas fairly close to those of their ancestors [ 21 ]. We speculate that these ancient practices might have promoted the inheritance of almost identical alleles, thereby increasing homozygosity and causing HW departure.…”

Exome Sequencing Data Analysis and a Case-Control Study in Mexican Population Reveals Lipid Trait Associations of New and Known Genetic Variants in Dyslipidemia-Associated Loci

“…This study included 2838 Mexican individuals belonging to the Mestizo cohorts Diabetes in Mexico Study (DMS, n = 968) and Mexico City Diabetes Study (MCDS, n = 796), published previously as part of the Slim Initiative in Genomic Medicine for the Americas (SIGMA) Type 2 Diabetes Consortium ( Estrada et al, 2014 ), as well as to the indigenous cohort Metabolic Analysis in an Indigenous Sample (MAIS, n = 1074) ( García-Ortíz et al, 2021 ). The sample design was previously described in Estrada et al and García-Ortiz et al ( Estrada et al, 2014 ; García-Ortíz et al, 2021 ). The MAIS sample belongs to 71 indigenous communities representing 60 ethnic groups from 10 linguistic families.…”

“…This investigation was approved by the local ethics and research committees from the National Institute of Genomic Medicine and was conducted according to the principles of the Declaration of Helsinki. The genetic structure of DMS and MCDS population was previously described, with a mean (SD) proportion of Amerindian ancestry of 66 ± 17%, whereas the proportion of Amerindian ancestry in the MAIS cohort was of 93.2 ± 8.7% ( Estrada et al, 2014 ; García-Ortíz et al, 2021 ).…”

“…The recent and complex admixture in the Mexican Mestizo population might have produced a high level of genetic heterogeneity in variants in lipid-related loci. Therefore, this study aimed to determine the frequency distribution of variants located at genes related to lipid traits in Mexican individuals, followed by an association testing and the identification of potential variants for lipemic traits, using previously published exome sequencing data ( Estrada et al, 2014 ; García-Ortíz et al, 2021 ).…”