The enzyme salivary amylase, encoded by the AMY1 gene, initiates the breakdown of starch into simpler sugars beginning in the oral cavity, an early and efficient step in carbohydrate digestion. The heightened copy number of AMY1 among Andean populations, averaging around 10 copies per genome, far exceeds that observed in most other global populations. This genomic architecture provides these individuals with enhanced starch-processing capabilities, likely conferring a significant survival and reproductive advantage during periods when starch-rich tubers became dietary mainstays under the challenging conditions of high-altitude life.

Evolutionary anthropologist Abigail Bigham, who led the research at UCLA, describes this adaptation as a striking example of the interplay between cultural practices and biological evolution. The domestication of the potato, an integral starch source first cultivated by Indigenous individuals of the Andes, transformed local diets and set the stage for selective pressures that favored those with increased enzymatic capacity for starch metabolism. These pressures, intensified by the physiological demands of hypoxia inherent to high-altitude environments, contributed to the sculpting of the human genome in this unique ecological niche.

The research methodology was rigorous, involving the collection of DNA samples from Quechua-speaking Indigenous Peruvians, whose genomes were analyzed alongside vast datasets encompassing a diverse array of modern human populations. This comparative genomic approach enabled the team to detect statistically robust signals of natural selection acting on the AMY1 gene cluster specifically within Andean groups. The findings highlight an evolutionary mechanism wherein individuals possessing approximately 10 or more copies of AMY1 exhibited a survival or reproductive advantage estimated at around 1.24% per generation, a significant rate given the timescale involved.

Notably, the study adds nuance to our understanding of the temporal context of AMY1 gene copy number variation. While the initial duplication event that gave rise to multiple AMY1 copies predates modern humans by hundreds of thousands of years—occurring at least 800,000 years ago—the selective enrichment of higher copy numbers within Andean populations is a relatively recent phenomenon. This enrichment likely coincided with the Neolithic agricultural revolution in the region, underscoring the profound influence of subsistence strategies on genomic evolution.

Omer Gokcumen, a co-corresponding author from the University at Buffalo, emphasizes the broader implications of this research. It exemplifies a rare and compelling instance where the direct effect of diet-induced natural selection can be measured and quantified at the genetic level, providing a model for understanding how human genomes continue to evolve in response to cultural innovations related to food production and consumption.

Understanding the genetic variation in AMY1 also sheds light on current human metabolic diversity and potential health impacts. Variability in amylase production influences digestive efficiency and may modulate the gut microbiome, affecting metabolic processes and susceptibility to diet-related diseases. This research invites further inquiry into gene-diet interactions and their ramifications for public health, particularly as global diets become increasingly homogenized with the ubiquity of processed, carbohydrate-rich foods such as French fries.

One particularly challenging aspect addressed by the researchers was disentangling the impact of natural selection from demographic effects introduced by European colonization, which dramatically reduced Indigenous population sizes and genetic diversity in the Americas. Employing state-of-the-art ultra-long DNA sequencing technologies and sophisticated statistical models allowed the team to conclusively attribute the heightened AMY1 copy numbers to ancient selection pressures rather than recent population bottlenecks.

The evolutionary narrative uncovered by this study reprises the concept that evolution is not an instantaneous engineer but a sculptor of pre-existing variation, gradually favoring advantageous traits across generations. The higher AMY1 copy number in modern Andean populations is thus the cumulative legacy of selective forces acting over millennia, favoring individuals capable of more efficient starch digestion amid an environment dominated by cold, hypoxia, and limited dietary resources.

Furthermore, the findings challenge simplistic notions within popular dietary discourse, such as the ‘paleo diet,’ which posits that human metabolism is optimized solely for Paleolithic-era foods predating agriculture. Instead, this work compellingly illustrates that human genetic adaptation is ongoing, incorporating evolutionary responses to post-agricultural dietary shifts within the relatively recent 10,000-year frame, thereby broadening our understanding of metabolic flexibility and resilience.

Beyond the scientific novelty, this research invites a re-examination of how cultural heritage and environmental constraints intersect to mold human biology. The Andean example underscores that cultural innovations—like potato cultivation—are not merely anthropological curiosities but active drivers of genetic change, reinforcing the co-evolutionary dance of humans and their ecosystems.

The extensive international collaboration underpinning this study involved experts from institutions spanning the Americas and Eurasia, reflecting the global relevance and interdisciplinary nature of contemporary evolutionary genomics. Supported by prominent funding bodies including the National Science Foundation, the National Institutes of Health, and the Leakey Foundation, this research not only enriches academic knowledge but also holds promise for informing medical and nutritional science in diverse populations.

As we move deeper into the era of precision medicine and personalized nutrition, insights gleaned from such evolutionary studies will be invaluable. Investigating the genetic determinants of dietary adaptation offers pathways to understanding differential health outcomes and tailoring interventions that respect both our genomic diversity and cultural identities. The story of the AMY1 gene in the Andes is a testament to the intricate and dynamic relationship between humans and their sustenance.

Subject of Research: Human evolutionary adaptation to diet and high-altitude environment in Indigenous Andean populations with a focus on the AMY1 gene involved in starch digestion.

Article Title: Indigenous Andeans’ high AMY1 gene copy number reveals ancient natural selection linked to potato domestication

News Publication Date: February 13, 2024

Web References:

• https://pubmed.ncbi.nlm.nih.gov/39882941/
• https://www.buffalo.edu/news/releases/2024/10/our-love-of-carbs-predate-agriculture-and-maybe-even-our-split-from-Neanderthals.html

References: Published in Nature Communications

Keywords: Indigenous Andes, AMY1 gene, starch digestion, natural selection, high-altitude adaptation, potato domestication, evolutionary genomics, gene-diet interaction, human metabolism, anthropological genetics, hypoxia adaptation

This landmark research, led by He, Zhang, Peng, and colleagues, introduced the SEA3K genome dataset—an extensive collection of whole-genome sequences drawn from 3,023 individuals representing 30 distinct MSEA populations. Using state-of-the-art deep short-read sequencing alongside long-read whole-genome sequencing on a subset of 37 individuals, the team achieved an unparalleled resolution in capturing both small-scale and large structural genomic variations. The scale and depth of these data represent a quantum leap forward in regional genomic research, filling critical gaps that have long hindered inclusive global genetic studies.

What makes the SEA3K dataset particularly striking is the staggering number of novel variants it contains. Across the genomes examined, researchers identified nearly 80 million small nucleotide variants and over 96,000 structural variants. Remarkably, more than 22 million of the small variants and approximately 24,600 structural variants were previously unreported, highlighting how underrepresented MSEA populations have been in global sequencing efforts. These unique variants are not merely catalog entries but provide vital clues about the distinct evolutionary trajectories shaped by the region’s complex demographic and environmental history.

The genetic heterogeneity captured in the SEA3K data is profound. Unlike regions characterized by homogenous genetic profiles, MSEA populations display a dynamic tapestry of genetic components, reflecting extensive historical interactions, migrations, and isolations. The analysis reveals that the genetic variation within this relatively confined geographical area rivals, and in some instances exceeds, the diversity seen across broader continental scales. This heterogeneity underscores the importance of localized genomic studies, as regional complexities can be easily missed or oversimplified in pan-global datasets.

Beyond descriptive genomics, the study illuminates the adaptive processes that have sculpted MSEA genomes in response to environmental and cultural pressures. Through rigorous scans for signals of Darwinian positive selection, the researchers pinpointed 44 genomic regions exhibiting strong evidence of recent adaptation. These regions collectively encompass 89 genes involved in a wide array of physiological domains, including immune response, metabolic pathways, and physical traits. Such findings furnish molecular-level insights into how MSEA populations have fine-tuned their biology to thrive in diverse ecological niches ranging from tropical forests to highland terrains.

One of the most intriguing facets of the SEA3K project is its contribution to understanding archaic human ancestry. Although it is well-established that modern humans interbred with archaic hominins such as Neanderthals and Denisovans, the patterns and extent of such introgressions in Asian populations remain areas of active research. The SEA3K data uncovered differentiated patterns of Denisovan genetic material across MSEA groups, lending strong support to the hypothesis that at least two distinct episodes of Denisovan admixture occurred in Asia. This nuanced picture challenges simplified models of archaic introgression, suggesting complex admixture events aligned with multiple waves of human expansion.

The study further identified genomic regions suggestive of adaptive archaic introgression. In other words, some Denisovan-derived genetic fragments appear to have been favored by natural selection in MSEA populations, potentially conferring advantages in immune defense or environmental adaptation. This intricate genomic interplay between ancient and modern humans highlights how archaic DNA contributions shape contemporary human variation beyond mere inheritance, actively influencing phenotypic and ecological outcomes.

Importantly, the SEA3K initiative addresses a critical equity gap in human genomics. Historically, large-scale databases such as the 1000 Genomes Project or gnomAD have been skewed towards populations of European descent, limiting the interpretive power of genetic studies globally. By enriching the catalog of variants with extensive data from MSEA populations, the study empowers researchers to better investigate complex diseases, pharmacogenomics, and population-specific adaptive traits relevant to the region’s inhabitants.

The integration of both short-read and long-read sequencing technologies also heralds a methodological advance. While short-read sequencing excels at detecting single nucleotide variants and small insertions or deletions, long-read sequencing enables accurate mapping of structural variants and complex genomic rearrangements that shorter reads might miss. The dual approach adopted here provides a comprehensive view of genomic architecture, uncovering layers of variation critical for understanding gene regulation, evolutionary dynamics, and disease susceptibility.

Furthermore, this dataset serves as a valuable resource for reconstructing the demographic history of Southeast Asia. The rich genetic variation and heterogeneous patterns observed imply ancient population splits, migrations, and admixture events that correspond with archaeological and linguistic evidence. Through population genetic modeling and comparative analyses, the SEA3K genomes can illuminate questions about the peopling of Southeast Asia, the spread of agriculture, and the interactions among early human groups in this climatically and culturally diverse region.

Looking ahead, the SEA3K genome dataset holds promise for catalyzing a new wave of genomic medicine tailored to Southeast Asian populations. By anchoring precision health initiatives in locally relevant genetic data, medical researchers can improve disease risk predictions, develop population-specific therapeutics, and ultimately enhance health equity. The dataset’s openness for further scientific exploration invites collaborations that will expand our understanding of human genetics beyond traditional geographic and ethnic boundaries.

In summary, the SEA3K project not only enriches the genomic narrative of Mainland Southeast Asia but also sets a precedent for integrative, inclusive, and technologically sophisticated genomic research. By revealing vast new layers of genetic diversity, selection, and archaic introgression, it empowers scientists worldwide to rethink human evolutionary history and health within one of the world’s most genetically rich, yet understudied, regions.

This transformative dataset is a clarion call to broaden the horizons of human genomics, reminding us that the story of humanity is far from fully told. As genomic technologies advance and databases grow ever more inclusive, the complex genetic mosaic of Mainland Southeast Asia—once overlooked—now stands poised to tell its many unique and vital chapters.

Subject of Research: Genome diversity and natural selection in Mainland Southeast Asia populations

Article Title: Genome diversity and signatures of natural selection in mainland Southeast Asia

Article References:
He, Y., Zhang, X., Peng, MS. et al. Genome diversity and signatures of natural selection in mainland Southeast Asia. Nature (2025). https://doi.org/10.1038/s41586-025-08998-w

Image Credits: AI Generated