Population history and gene divergence in Native Mexicans inferred from 76 human exomes

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 kya 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.

Dietary, Cultural and Pathogens-related Selective Pressures Shaped Differential Adaptive Evolution Among Native Mexican Populations

“…Such a fragmented demographic history of Mexican groups was proposed also by previous studies, which pointed to a genetic structure of Native Mexicans that is more related to their territories' orography rather than to cultural/linguistic differences (Gorostiza et al 2012;González-Martín and Gorostiza 2013;Moreno-Estrada et al 2014;Rangel-Villalobos et al 2016). In particular, our findings are consistent with results from the analysis of exome sequence data of Mexican indigenous populations, including TAR, HUI, TRQ and MYA, which inferred that northern and southern ancestral Native Mexican groups split approximately 7.2 thousand years ago (KYA) and further diverged locally around 6.5 and 5.7 KYA, respectively (Ávila-Arcos et al 2020). Moreover, more recent differentiation between HUI/PUR (3.4 KYA), NAH/PUR (2.2 KYA), and HUI/NAH (357 YA) seems to support our assumption that these CMC populations largely shared a common evolutionary history since they diverged from NMC and SMC groups (González-Martín and Gorostiza 2013).…”

“…Admixed) individuals, in whom the effects of recent ecological transitions and Westernization of lifestyles have been predominantly investigated (Rivera et al 2004;Aguilar-Salinas et al 2011;Weissglas-Volkov et al 2013;Ko et al 2014).Conversely, few studies have focused so far on Native Mexican populations (Acuña-Alonzo et al 2010; Lara-Riegos et al 2015;Romero-Hidalgo et al 2017), who are instead the most suitable groups to be considered for inferring the pre-Columbian evolutionary history of the ancestors of modern Mexican people (Moreno-Estrada et al 2014;Ávila-Arcos et al 2020). Interestingly, these studies revealed a complex genetic structure of the main indigenous groups that have long-inhabited the present-day Mexico's territory, which is tightly related to the well-known historical, cultural and demographic processes they have experienced (Moreno-Estrada et al 2014;Romero-Hidalgo et al 2017;Ávila-Arcos et al 2020). In particular, a northwest-southeast gradient of Mexican variation has been described, along with an overall differentiation in the proportions of ancestry components between northern, central and southern populations, which is clearly distinguishable in both Native and geographically-neighboring Mexican Mestizo groups (Rubi-Castellanos et al 2009;Moreno-Estrada et al 2014).Major genetic divergence between Aridoamerican (i.e.…”

“…central/southern) indigenous populations has been previously suggested to be ascribable also to the contrasting climate and ecological conditions characterizing these Mexican macro-regions (Gorostiza et al 2012; González-Martin et al 2015). Nonetheless, the adaptive evolution of Native Mexican ancestors in response to local environmental and/or cultural selective pressures has been scarcely investigated so far (Ávila-Arcos et al 2020). Unfortunately, this has limited also the identification of the genetic determinants of important biological features of present-day Native and Mestizo Mexican people.…”

“…Unfortunately, this has limited also the identification of the genetic determinants of important biological features of present-day Native and Mestizo Mexican people. In particular, variation underlying adaptive traits that have been shaped by natural selection in relation to the ancestral milieu of these human groups might represent an important reservoir of alleles/haplotypes with potential biomedical relevance (Sazzini et al 2016;Ávila-Arcos et al 2020;Sazzini et al 2020;Landini et al 2020). In fact, the rapid and substantial modifications occurred in modern Mexican societies might have turned some of these biological adaptations into unfavorable (i.e.…”

Association Between Breastfeeding and Child Stunting in Mexico

“…Additionally, in our subsample, the highest proportion of short stature women was found among indigenous women, which may further aggravate child stunting outcomes. Recent genetic analyses have identified idiopathic short stature among the Mexican indigenous population across generations [ 36 ]. While this trait may partially explain offspring’s short stature in this population, it does not fully account for the persistence of the intergenerational effect of undernutrition and its negative cognitive and developmental outcomes, which continue to be pervasive in this group in Mexico.…”