Abstract The study of mitochondrial DNA is a valuable tool to delve into the demographic history of human populations. Particularly in the Americas, five widespread Native American specific mitochondrial lineages have been identified. Here we included the complete mitogenome sequencing of 572 Indigenous individuals belonging to 60 populations spanning the Mexican territory. Our results show a great diversity of matrilineages widespread across the country, revealing shared mtDNA haplogroups in populations from distant regions. We identified all the five main Native American haplogroups clades, including 83 different subhaplogroups, from which nine are novel. The most frequent of the novel haplogroups was A2+64. A phylogenetic inference suggests that A2+64 comes from an ancestral maternal lineage that spread into the Caribbean islands. Additionally, a demographic reconstruction from whole mitogenomes showed an exponential increase in female Ne around 10 Ka ago in all the tested regions. All these findings suggest a genetic persistence through Mexico and possibly the Americas, in agreement with the model of the Mesoamerican-related expansion into the Caribbean and South America.

Whole mitogenome analysis highlights demographic history and shared connections among distal Indigenous groups of Mexico Complete mitogenome sequencing from 60 Mexican Native American groups