In 1428 AD, while King Alfonso V was ordering Sicilian Jews into conversion sermons and the Ottomans were consolidating in Europe, the city-states of Tenochtitlan, Texcoco, and Tlacopan formed the Triple Alliance, which became the Aztec empire and ruled the Valley of Mexico until the Spaniards arrived a century later. 

The term 'Aztec' has become a little confusing since then. There were no 'Aztec' people, the people of Mexico primarily made up what were later called Aztecs, and the Aztecs were made up of many cultures, they were just dominated by conquering city-states. Historians call such a structure a hegemonic empire as compared to the traditional meaning like with Rome or Mongolia.

By the time of the arrival of the Spaniards in 1519, the Aztecs were spread from central Mexico to Guatemala, El Salvador and Honduras. The city-states (Tenochtitlan was the military power) had annexed numerous city-states in the Basin of Mexico. But the demographic consequences of the expansion have remained speculation. 16th century documents suggest that Xaltocan's conquest and subsequent incorporation into the Aztec empire led to a replacement of its original Otomí population but archaeological evidence shows that some of the original population may have remained at the town under Aztec rule.

Researchers writing in American Journal of Physical Anthropology set out to try and clear up some of the mystery. They analyzed ancient DNA from 25 individuals recovered from three houses occupied (and rebuilt) between 1240 and 1521 AD. They divided the DNA into two temporal groups, pre -and post-conquest by the Aztecs. They determined the mitochondrial DNA haplogroup of each individual and identified haplotypes based on 372 base pair sequences and their findings showed that the residents of the houses before and after the Aztec conquest were distinct haplotypes that are not closely related, and the mitochondrial compositions of the temporal groups are statistically different.

What does that mean?  Someone took over the house, obviously, after the Aztec conquest. Their study indicates that the Aztec expansion caused demographic changes - and therefore genetics changes among the people of Xaltocan as well. It also may be because the Otomi's were regarded as fierce warriors, similar to Jaguars and Eagles, and so may have moved for those reasons.  Otomi were also regarded by the other Aztecs as polygamous and sexually immoral, which has its own interesting genetic effects. Regardless, the Otomi overall were not all that happy with the Aztecs - when the Spaniards came to Mexico, they sided with the new invaders as being superior to the old ones.

Citation: Jaime Mata-Míguez, Lisa Overholtzer, Enrique Rodríguez-Alegría, Brian M. Kemp, Deborah A. Bolnick, 'The genetic impact of aztec imperialism: Ancient mitochondrial DNA evidence from Xaltocan, Mexico', American Journal of Physical Anthropology, DOI: 10.1002/ajpa.22152