If you’ve ever had difficulty reducing your carbohydrate intake, ancient DNA could be to blame.
It has long been known that humans carry multiple copies of a gene that allows us to begin breaking down complex carbohydrate starch in the mouth, providing the first step in the metabolization of starchy foods such as bread and pasta. However, it has proven notoriously difficult for researchers to determine how and when the number of these genes expanded.
Now, a new study led by the University at Buffalo and the Jackson Laboratory (JAX) reveals how duplication of this gene, known as the salivary amylase gene (AMY1), may not only have helped shape human adaptation to food rich in starch. , but it may have occurred more than 800,000 years ago, long before the arrival of agriculture.
Reported today in the advanced online edition of October 17, Science, Ultimately, the study shows how early duplications of this gene set the stage for the wide genetic variation that still exists today, influencing how effectively humans digest starchy foods.
“The idea is that the more amylase genes you have, the more amylase you can produce and the more starch you can effectively digest,” says the study’s corresponding author, Omer Gokcumen, PhD, professor in the UB Department of Biological Sciences. Faculty of Arts and Sciences.
Amylase, the researchers explain, is an enzyme that not only breaks down starch into glucose, but also gives bread flavor.
Gokcumen and his colleagues, including co-senior author Charles Lee, Professor and Robert Alvine Family Chair at JAX, used optical genome mapping and long-read sequencing, a crucial methodological advance to map the AMY1 gene region with extraordinary detail. Traditional short-read sequencing methods have difficulty accurately distinguishing between gene copies in this region due to their nearly identical sequence. However, long-read sequencing allowed Gokcumen and Lee to overcome this challenge in modern-day humans, providing a clearer picture of how AMY1 duplications evolved.
Ancient hunter-gatherers and even Neanderthals already had multiple copies of AMY1
By analyzing the genomes of 68 ancient humans, including a 45,000-year-old sample from Siberia, the research team found that pre-agricultural hunter-gatherers already had an average of four to eight copies of AMY1 per diploid cell, suggesting that The humans were already walking. around Eurasia with a wide variety of high AMY1 copy numbers long before they began domesticating plants and eating excessive amounts of starch.
The study also found that duplications of the AMY1 gene occurred in Neanderthals and Denisovans.
“This suggests that the AMY1 gene may have first duplicated more than 800,000 years ago, long before humans split from Neanderthals and much earlier than previously thought,” says Kwondo Kim, one of the lead authors of this study from the Lee Lab at JAX. .
“The initial duplications in our genomes laid the foundation for significant variation in the amylase region, allowing humans to adapt to changing diets as starch consumption increased dramatically with the advent of new technologies and lifestyles,” Gokcumen adds.
The seeds of genetic variation.
The initial duplication of AMY1 was like the first ripple in a pond, creating a genetic opportunity that later shaped our species. As humans spread across different environments, flexibility in AMY1 copy number provided an advantage in adapting to new diets, particularly those high in starch.
“After the initial duplication, which gave rise to three copies of AMY1 in one cell, the amylase locus became unstable and began to create new variations,” says Charikleia Karageorgiou, one of the main authors of the study at the UB. “From three copies of AMY1, you can get up to nine copies, or even go back to one copy per haploid cell.”
The complicated legacy of agriculture
The research also highlights how agriculture affected AMY1 variation. While early hunter-gatherers had multiple gene copies, European farmers saw an increase in the average copy number of AMY1 over the past 4,000 years, likely due to their starchy diets. Gokcumen’s previous research showed that domesticated animals that live alongside humans, such as dogs and pigs, also have higher copy numbers of the amylase gene compared to animals that do not rely on starch-rich diets.
“Individuals with a higher copy number of AMY1 probably digested starch more efficiently and had more offspring,” says Gokcumen. “Ultimately, their lineages fared better over a long evolutionary period than those with lower copy numbers, spreading the number of AMY1 copies.”
The findings are consistent with a study led by the University of California, Berkeley, published last month in Nature, which found that humans in Europe expanded their average number of AMY1 copies from four to seven over the past 12,000 years.
“Given the key role of AMY1 copy number variation in human evolution, this genetic variation presents an exciting opportunity to explore its impact on metabolic health and uncover the mechanisms involved in starch digestion and glucose metabolism. ” says Feyza Yilmaz, associate computational scientist at JAX and lead author of the study. “Future research could reveal their precise effects and the timing of selection, providing critical insights into genetics, nutrition and health.”
Other UB authors who participated in the study include doctoral students Petar Pajic and Kendra Scheer.
The research was a collaboration with the University of Connecticut Health Center and was supported by the National Science Foundation and the National Human Genome Research Institute, National Institutes of Health.