{Reference Type}: Historical Article {Title}: Ancient DNA Studies in Pre-Columbian Mesoamerica. {Author}: Roca-Rada X;Souilmi Y;Teixeira JC;Llamas B; {Journal}: Genes (Basel) {Volume}: 11 {Issue}: 11 {Year}: 11 2020 13 {Factor}: 4.141 {DOI}: 10.3390/genes11111346 {Abstract}: Mesoamerica is a historically and culturally defined geographic area comprising current central and south Mexico, Belize, Guatemala, El Salvador, and border regions of Honduras, western Nicaragua, and northwestern Costa Rica. The permanent settling of Mesoamerica was accompanied by the development of agriculture and pottery manufacturing (2500 BCE-150 CE), which led to the rise of several cultures connected by commerce and farming. Hence, Mesoamericans probably carried an invaluable genetic diversity partly lost during the Spanish conquest and the subsequent colonial period. Mesoamerican ancient DNA (aDNA) research has mainly focused on the study of mitochondrial DNA in the Basin of Mexico and the Yucatán Peninsula and its nearby territories, particularly during the Postclassic period (900-1519 CE). Despite limitations associated with the poor preservation of samples in tropical areas, recent methodological improvements pave the way for a deeper analysis of Mesoamerica. Here, we review how aDNA research has helped discern population dynamics patterns in the pre-Columbian Mesoamerican context, how it supports archaeological, linguistic, and anthropological conclusions, and finally, how it offers new working hypotheses.