The origins predate agriculture and maybe even our split from Neanderthals
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| Organic Oasis Mag |
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 metabolizing starchy foods like bread and
pasta. However, it has been 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 the duplication of this gene -- known as
the salivary amylase gene (AMY1) -- may not only have helped shape human
adaptation to starchy foods, but may have occurred as far back as more than
800,000 years ago, long before the advent of farming.
Reported today in the Oct. 17 advanced online issue of Science, the study ultimately showcases 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 digest
effectively," says the study's corresponding author, Omer Gokcumen, PhD,
professor in the Department of Biological Sciences, within the UB College of
Arts and Sciences.
Amylase, the researchers explain, is an enzyme that not only
breaks down starch into glucose, but also gives bread its taste.
Gokcumen and his colleagues, including co-senior author,
Charles Lee, professor and Robert Alvine Family Endowed Chair at JAX, used
optical genome mapping and long-read sequencing, a methodological breakthrough
crucial to mapping the AMY1 gene region in extraordinary detail. Traditional
short-read sequencing methods struggle to accurately distinguish between gene
copies in this region due to their near-identical sequence. However, long-read
sequencing allowed Gokcumen and Lee to overcome this challenge in present-day
humans, providing a clearer picture of how AMY1 duplications evolved.
Ancient hunter-gatherers and even Neanderthals already
had multiple AMY1 copies
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 AMY1
copies per diploid cell, suggesting that humans were already walking around
Eurasia with a wide variety of high AMY1 copy numbers well before they started
domesticating plants and eating excess amounts of starch.
The study also found that AMY1 gene duplications occurred in
Neanderthals and Denisovans.
"This suggests that the AMY1 gene may have first
duplicated more than 800,000 years ago, well before humans split from
Neanderthals and much further back than previously thought," says Kwondo
Kim, one of the lead authors on this study from the Lee Lab at JAX.
"The initial duplications in our genomes laid the
groundwork for significant variation in the amylase region, allowing humans to
adapt to shifting diets as starch consumption rose 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, the flexibility in the number of AMY1
copies provided an advantage for adapting to new diets, particularly those rich
in starch.
"Following the initial duplication, leading to three
AMY1 copies in a cell, the amylase locus became unstable and began creating new
variations," says Charikleia Karageorgiou, one of the lead authors of the
study at UB. "From three AMY1 copies, you can get all the way up to nine
copies, or even go back to one copy per haploid cell."
The complicated legacy of farming
The research also highlights how agriculture impacted AMY1
variation. While early hunter-gatherers had multiple gene copies, European
farmers saw a surge in the average number of AMY1 copies over the past 4,000
years, likely due to their starch-rich diets. Gokcumen's previous research
showed that domesticated animals living alongside humans, such as dogs and
pigs, also have higher amylase gene copy numbers compared to animals not
reliant on starch-heavy diets.
"Individuals with higher AMY1 copy numbers were likely
digesting starch more efficiently and having more offspring," Gokcumen
says. "Their lineages ultimately fared better over a long evolutionary
timeframe than those with lower copy numbers, propagating the number of
the AMY1 copies."
The findings track with a University of California,
Berkeley-led study published last month in Nature, which found that humans in
Europe expanded their average number of AMY1 copies from four to seven over the
last 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, an associate
computational scientist at JAX and a lead author of the study. "Future
research could reveal its precise effects and timing of selection, providing
critical insights into genetics, nutrition, and health."
Other UB authors on the study include PhD 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.
