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The Genetic Legacy of Starch Digestion: How Ancient Duplications Shape Modern Humans

Struggling with carbohydrate consumption? New research suggests that a significant aspect of this challenge lies in our genetic makeup, shaped by ancient DNA. Humans possess multiple copies of the salivary amylase gene, which plays a critical role in the initial breakdown of starchy foods such as bread and pasta in the mouth.

Despite this understanding, the timeline and mechanisms behind the expansion of these gene copies have remained elusive. A recent study undertaken by researchers from The University of Buffalo and The Jackson Laboratory provides new insights into how early duplications of this gene have led to significant genetic variability that affects starch digestion even today.

Published online in the October 17 issue of Science, the study reveals that duplications of the AMY1 gene—associated with salivary amylase—may date back over 800,000 years, long before agriculture emerged. Omer Gokcumen, a professor at UB, explains, “The more amylase genes you possess, the higher your amylase production, which translates to improved starch digestion capability.” This enzyme is not only central to digesting starch but also contributes to the pleasant flavors of baked goods.

Utilizing advanced techniques like optical genome mapping and long-read sequencing, researchers overcame the challenges of traditional sequencing methods that often struggled to differentiate the nearly identical gene copies in this region. Gokcumen and co-senior author Charles Lee aimed to illuminate the evolution of AMY1 duplications in contemporary humans.

Insights from Ancient Genomes

The investigation analyzed the genomes of 68 ancient humans, including a 45,000-year-old specimen from Siberia. Notably, the study found that pre-agricultural hunter-gatherers possessed an average of four to eight AMY1 gene copies per cell, highlighting how variations were already present in human populations long before the advent of agriculture.

Moreover, the study identified AMY1 duplications in Neanderthals and Denisovans, suggesting these duplications began over 800,000 years ago, much earlier than previously believed. Kwondo Kim, a lead author of the study, commented, “The original duplications set the foundation for the remarkable diversity observed in the amylase gene region, enabling humans to adapt to diverse diets that increasingly included starch.”

Fostering Genetic Variation

The initial duplication of the AMY1 gene can be likened to a pebble dropped in water, creating ripples that facilitated genetic variation. As human populations migrated and settled in different environments, the flexibility in AMY1 gene copy numbers offered advantages in adapting to varied diets rich in starch.

Charikleia Karageorgiou, a lead author from UB, noted that once the AMY1 gene had three copies, it became prone to instability, allowing the development of new variations. This process could lead to a range of copy numbers, from as few as one to as many as nine in individual cells.

The Impact of Agriculture

The study also emphasizes agriculture’s role in shaping AMY1 variation. Although hunter-gatherer populations already exhibited multiple gene copies, farmers in Europe experienced an increase in their average number of AMY1 copies over the last 4,000 years, likely due to starch-rich diets. Gokcumen’s prior research has indicated that domesticated animals living closely with humans also have higher AMY1 copy numbers compared to their counterparts that thrived on less starch-heavy diets.

“Individuals possessing higher AMY1 copy numbers likely had an evolutionary advantage, effectively digesting starch, leading to increased reproductive success,” Gokcumen suggested. Thus, these lineages outperformed others over time, enhancing the prevalence of AMY1 duplications.

This narrative aligns with another recent study from the University of California, Berkeley, which reported that the average AMY1 copy number among European populations rose from four to seven in the last 12,000 years.

Exploring the Future of Nutritional Genetics

Given the crucial role of AMY1 in human evolution, this genetic variation opens avenues for further research into its implications for metabolic health. Feyza Yilmaz, a computational scientist at JAX and a lead author of the study, expressed that understanding this genetic variation could yield valuable insights into nutrition, digestion, and overall health.

“Future investigations may provide clarity on the timing and nature of selection pressures on AMY1 variations, turning attention to the intricate relationship between genetics and nutrition in human health,” Yilmaz stated.

More information: Feyza Yilmaz et al, Reconstruction of the human amylase locus reveals ancient duplications seeding modern-day variation, Science (2024). DOI: 10.1126/science.adn0609. www.science.org/doi/10.1126/science.adn0609

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phys.org