New research by a multinational team of scientists including two from the University of Tennessee Health Science Center reveals agriculture shaped human evolution by drastically boosting our ability to digest carbohydrates.
Associate Professor Erik Garrison, PhD, and postdoctoral scholar Andrea Guarracino, PhD, both in the Department of Genetics, Genomics and Informatics, worked with researchers from the United States and Italy to find that humans have significantly increased the number of genes responsible for producing enzymes that break down starch, called amylases, over the last 12,000 years. Dr. Garrison and Peter Sudmant, PhD, of the University of California, Berkeley, led the study.
“We see that agriculture is correlated with a big increase in the frequency of genomes that have more copies of amylase. Using new pangenome resources, our study shows this is one of the strongest known cases of selection in humans,” Dr. Garrison said.
This evolutionary shift coincided with the spread of agriculture from the Middle East into Europe, as societies transitioned from hunter-gatherers to farmers who relied on grains like wheat and other high-carbohydrate staples. The study, published in Nature, explains that Europeans carried on average a total of eight copies of amylase genes 12,000 years ago, compared to more than 11 copies today.
“Amylase is the first step in our digestion of starches. It is the most common protein found in our saliva and is also expressed in our blood. We need it to break down complex carbohydrates, starches, into simpler sugars that our cells can use for energy,” Dr. Garrison said. “Increasing the number of copies of the amylase gene increases the amount of amylase enzymes in our saliva and blood. This might make it easier for us to digest high-starch diets that became common after the advent of agriculture, change the flavor of starchy food, or have other effects on our oral microbiome.”
The adaptation to extract more energy from starchy foods gave early agricultural communities a crucial survival advantage. Similar patterns were observed in agricultural societies worldwide, no matter what starchy food the society domesticated, suggesting that the development of farming prompted parallel genetic changes across different populations.
The findings come as a result of the first-ever human pangenome reference, a draft of which was published in Nature last year by the Human Pangenome Reference Consortium. Built using technical tools Dr. Garrison and other researchers in his department created, the pangenome reference uses complete genome assemblies to provide a diverse look at the genetic makeup of humans, allowing scientists to understand parts of the human genome that could not be seen before.
“It has long been hypothesized that the copy number of amylase genes had increased in Europeans since the dawn of agriculture, but we had never been able to sequence this locus fully before. It is extremely repetitive and complex,” Dr. Sudmant said. “Now, we’re finally able to fully capture these structurally complex regions, and with that, investigate the history of selection of the region, the timing of evolution and the diversity across worldwide populations. Now, we can start thinking about associations with human disease.”
“We’re really excited about how far we can push our new methods to identify new genetic causes of disease.”
Dr. Erik Garrison
According to Dr. Garrison, the research offers a way to explore other regions of the genome, such as those related to the immune system, skin pigmentation, and mucus production, which have experienced rapid gene duplication in recent human history. He believes this work in human evolutionary genomics will favorably impact current and future health care. Furthermore, the findings reveal that animals living alongside humans – such as dogs, pigs, and rodents – developed extra amylase genes to process discarded human food, showing how evolution extends beyond our species.
“This is really the frontier, in my opinion,” Dr. Garrison said. “We can, for the first time, look at all of these regions that we could never look at before, and not just in humans – other species, too. Human disease studies have really struggled in identifying associations at complex loci, like amylase. Because the mutation rate is so high, traditional association methods can fail. We’re really excited about how far we can push our new methods to identify new genetic causes of disease.”
Other authors of the paper include UC Berkeley postdoctoral fellows Runyang Nicolas Lou, PhD, and Joana Rocha, PhD; UC Berkeley graduate student Alma Halgren; Davide Bolognini, PhD, and Alessandro Raveane, PhD, of Human Technopole in Milan, Italy; Nicole Soranzo, PhD, of Human Technopole and the University of Cambridge in the United Kingdom; and Chen-Shan Chin, PhD, of the Foundation for Biological Data Science in Belmont, California.