The Andes highlands started to homogenize around Y1K.
There is lots of differentiation between populations at the geographic boundary between the Andres highlands and the Amazonian region. Unsurprisingly, people in the highlands have high altitude adaptation genes, while people in the Amazon has infectious disease resistance genes, that are absent in their respective counterparts.
But, there is evidence of admixture between these populations in the northern coastal part of the South American continent where geographic barriers were not so great and there is archaeologically attested interactions between the people of the Pacific coast of South America and Amazonian peoples.
The sample size is 363 modern genomes from diverse populations with about a fifth of them from a prior study.
It is also worth noting as an aside that European admixture is quite thin relative to what one might naively expect in the studied populations, in both regions, except for a small subset of the Fertile Andes, and that African admixture is thin across the board in this region.
Genetic structure and gene flow of Western South American natives.
Eighteen native groups along the Coast, Andes, and Amazon regions were sampled. A) Grey dashed line in the center shows the division between Fertile Andes and Arid Andes. We showed the geographical distribution coupled with ADMIXTURE patterns for the lowest cross-validation value (K=5) using the dataset of 1.9M unlinked SNPs (including Native Americans, Europeans, and Africans). Blue and green dashed lines delimited the groups that showed highly significant value for the gene flow test (|Z score| > 4). Matsiguenka 1= Matsiguenkas-Sepahua, Matsiguenkas 2= Matsiguenkas-Shimaa B) Haplotype based inference of ancestry profile for each Native American population, each bar corresponds to the ancestry composition for a native population. For this analysis, Matsiguenka samples were merged into one. Colors for the ancestry profile correspond to the proportion of DNA shared between the population and donor groups detailed in the legend of section A.
Western South America was one of the worldwide cradles of civilization. The well known Inca Empire was the tip of the iceberg of a cultural and biological evolutionary process that started 14-11 thousand years ago. Genetic data from 18 Peruvian populations reveal that: (1) The between-population homogenization of the central-southern Andes and its differentiation with respect to Amazonian populations of similar latitudes do not extend northward. Instead, longitudinal gene flow between the northern coast of Peru, Andes and Amazonia accompanied cultural and socioeconomic interactions revealed by archeological studies. This pattern recapitulates the environmental and cultural differentiation between the fertile north, where altitudes are lower; and the arid south, where the Andes are higher, acting as a genetic barrier between the sharply different environments of the Andes and Amazonia (2). The genetic homogenization between the populations of the arid Andes is not only due to migration during the Inca Empire or the subsequent colonial period. It started at least during the earlier expansion of the pre-Inca Wari Empire (600-1000 YBP) (3) This demographic history allowed for cases of positive natural selection in the high and arid Andes vs. the low Amazon tropical forest: in the Andes, HAND2-AS1 (heart and neural crest derivatives expressed 2 antisense RNA1, related with cardiovascular function) and DUOX2 (dual oxidase 2, related to thyroid function and innate immunity) genes; in the Amazon, the gene encoding for the CD45 protein, essential for antigen recognition by T/B lymphocytes in viral-host interaction, consistent with the host-virus arms race hypothesis.
Victor Borda, et al., "The genetic structure and adaptation of Andean highlanders and Amazonian dwellers is influenced by the interplay between geography and culture" bioRxiv (January 31, 2020) doi: https://doi.org/10.1101/2020.01.30.916270
The body text introduction from the paper provides good historical context for the findings (citations omitted):
Western South America was one of the cradles of civilization in the Americas and the world. When the Spaniard conqueror Francisco Pizarro arrived in 1532, the pan-Andean Inca Empire ruled in the Andean region and had achieved levels of socioeconomic development and population density unmatched in other parts of South America. However, the Inca Empire, which lasted for around 200 years, with its emblematic architecture such as Machu Picchu and the city of Cuzco, was just the tip of the iceberg of a millenary cultural and biological evolutionary process. This process started with the peopling of the region (hereafter called western South America), that occurred 14–11 thousand years ago, involving the entire Andean region and its adjacent and narrow Pacific Coast.
Tarazona-Santos et al. proposed that cultural exchanges and gene flow along time have led to a relative genetic, cultural, and linguistic homogeneity between the populations of western South America compared with those of eastern South America (a term that hereafter refers to the region adjacent to the eastern slope of the Andes and eastward, including the Amazonia), where populations remained more isolated from each other. For instance, only two languages (Quechua and Aymara) of the Quechumaram linguistic stock predominate in the entire Andean region, whereas in eastern South America natives speak a different and broader spectrum of languages classified into at least four linguistic families. This spatial pattern of genetic diversity and its correlation with geography, environmental, linguistic and cultural diversity was confirmed, enriched and rediscussed by us and others.
There are pending issues: First, whether the dichotomic organization of genetic variation characterized by the between-population homogeneous Southern Andes vs. between-population heterogeneous Central Amazon, extends northward. This is important because scholars from different disciplines emphasize that western South America is not latitudinally homogeneous, differentiating a northern and in general lower and wetter fertile Andes and a southern, higher and more arid Andes. These environmental and latitudinal differences are correlated with demography and culture, including different spectra of domesticated plants and animals. Indeed, the development of agriculture, of the first urban centers such as Caral and its associated demographic growth, occurred earlier in the northern Fertile Andes (around 5ky ago) than in the southern arid Andes (and their associated Coast), with products such as cotton, beans, and corn domesticated in the fertile north and the potato and South American camelids in the arid south. In human population genetics studies, the region where the between-population homogeneity was ascertained by Tarazona-Santos et al. was the arid Andes.