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(https://directorsblog.nih.gov/2024/11/07/salivary-enzyme-behind-our-carb-cravings-may-have-unexpectedly-ancient-history/) Salivary Enzyme Behind Our Carb Cravings May Have Unexpectedly Ancient History
Nov 7th 2024, 09:00

Credit: Donny Bliss/NIH, Natalia/Adobe Stock

Digestion involves much more than just your stomach. The (https://www.niddk.nih.gov/health-information/digestive-diseases/digestive-system-how-it-works) digestive process that fuels your body begins in your mouth each time you take a bite of food and chew. An enzyme in your saliva, called amylase, then starts to break down complex carbohydrates—or starches found in many fruits, vegetables, and grains—into simpler sugars to give you their sweet flavor followed by a burst of energy.

Amylase is the reason we’re so good at turning starch into calories, but it isn’t the same for everyone. There’s plenty of genetic variation in the number of salivary amylase genes (AMY1) our cells carry and, therefore, in how much of this essential starch-busting enzyme people have. Studies have suggested a link between changes in amylase gene copy numbers over time and both the rise of agriculture and starch-heavy diets. Now a study in (https://www.science.org/doi/10.1126/science.adn0609) Science, supported in part by NIH, suggests that extra copies of AMY1 are not only connected to our ability to effectively digest carbs, but also may be more ancient than previously known, arising even before modern humans split from Neanderthals and long before the advent of farming.

The new findings come from a research team led by (https://arts-sciences.buffalo.edu/biological-sciences/faculty/faculty-directory/omer-gokcumen.html) Omer Gokcumen at The University of Buffalo, NY, and (https://www.jax.org/research-and-faculty/faculty/charles-lee) Charles Lee of The Jackson Laboratory for Genomic Medicine, Farmington, CT. While an earlier study linked AMY1 copy numbers with variation in starchy diets, researchers hadn’t been able to sequence the DNA with sufficient precision to get all the details. Newer methods make it possible to read longer stretches of DNA, bringing variation in the precise number of AMY1 copies into clearer view.

In DNA sequences from 98 individuals, the researchers identified 30 distinct versions of amylase genes known as haplotypes. A haplotype is a collection of genes and their variants that are close enough together on a chromosome that they tend to be inherited together. These collections of amylase genes varied considerably in length and the number of amylase gene copies they contained, ranging from two copies in each cell up to 16.

The researchers then compared the modern-day amylase genes to publicly available DNA sequences from 68 ancient human samples obtained from preserved remains. This revealed that ancient hunter-gatherers already had six to eight AMY1 copies long before people started growing crops and eating high amounts of starch. In fact, genetic variation underlying the production of this enzyme had already spread across Eurasia as far back as 45,000 years ago. However, the new analyses do show an increase in amylase gene copy numbers in the last 4,000 years, as people took up farming.

The study team went on to uncover evidence that the expansion of amylase genes apparently has a longer history than anyone had suspected. Intriguingly, they found three copies of AMY1 in the DNA of three of six Neanderthals and one Denisovan. Neanderthals and Denisovans are both extinct relatives of early humans. The findings suggest that an extra copy of the amylase gene may have arisen as long as 800,000 years ago. The researchers also described how those first extra AMY1 copies could lead to their continued duplications or deletions to produce the wide variation in amylase gene copy numbers seen among modern humans.

This variation in amylase genes would have afforded our ancestors dietary flexibility, allowing them to adapt as diets changed over time. But these discoveries aren’t only fascinating from an evolutionary or historical point of view. They may also lead to new understandings of genetic differences among people today, with potentially important implications for our metabolisms, nutrition, and health.

Reference:

Yılmaz F, et al. (https://pubmed.ncbi.nlm.nih.gov/39418342/) Reconstruction of the human amylase locus reveals ancient duplications seeding modern-day variation. Science. DOI: 10.1126/science.adn0609 (2024).

NIH Support: National Human Genome Research Institute, National Institute of General Medical Sciences

Forwarded by:
Michael Reeder LCPC
Baltimore, MD

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