How agriculture helped humans evolve to get more energy from carbohydrates

Our bodies absolutely need carbohydrates for energy. It’s a matter of survival. So much so that some human populations have increased the number of genes that help break down starches and sugars over the past 12,000 years. In that time, Europeans have gone from having an average of eight genes that break down starch to more than 11.

The adaptation follows the shift from a hunter-gatherer lifestyle to a more agrarian one, as farming spread across Europe from the Middle East. Carbohydrate-rich staples such as wheat increased dramatically in the human diet, and the ability to efficiently absorb all that energy proved advantageous. The findings are detailed in a study published Sept. 4 in the journal Nature.

Focusing on the “amylase locus”

Some of the approximately 19,900 known genes in the human genome can create the specific proteins that a gene codes for, called enzymes. Enzymes have a variety of functions, and amylase is the enzyme that helps the body break down carbohydrates. Amylase is produced in saliva and the pancreas to digest starch into sugar, which is the body’s fuel.

“If you take a piece of dry pasta and put it in your mouth, over time it will become a little sweet,” Peter Sudmant, a co-author of the study and a biologist at the University of California, Berkeley, said in a statement. “It’s the salivary enzyme amylase that breaks down starches into sugars. That happens in all humans, as well as other primates.”

(Related: Is butter a carbohydrate?)

Having more copies of a gene usually means that an organism has higher levels of the proteins that the genes code for specific enzymes. The genomes of bonobos, chimpanzees, and Neanderthals all have one copy of the AMY1 gene. This gene on chromosome 1 codes for salivary amylase. Their genomes also have one copy of the two pancreatic amylase genes, AMY2A and AMY2B. These three genes are located near each other in a region of the primate genome that scientists call the amylase locus. However, human genomes are a little different.

“Our study found that each copy of the human genome contains one to 11 copies of AMY1, zero to three copies of AMY2A, and one to four copies of AMY2B,” study co-author and UC Berkeley postdoctoral fellow Runyang Nicolas Lou said in a statement. “Copy number is correlated with gene expression and protein level, and therefore with the ability to digest starch.”

Using genetic analysis, the team found that about 12,000 years ago, humans across Europe had an average of four copies of the salivary amylase gene. Over time, that number has increased to about seven. The combined copy number of the two pancreatic amylase genes also increased by half a gene on average. This increase in carb genes suggests that there must be a powerful survival advantage to having chromosomes with multiple copies of amylase genes.

Lifestyle changes

Importantly, the team also found evidence of an increase in amylase genes in other agricultural populations around the world. The region of chromosomes where these amylase genes are located also appears similar across all of these populations, no matter which starchy plant was domesticated in that culture.

According to the team, this shows that as agriculture emerged in populations around the world, it appears to have rapidly changed the human genome in remarkably similar ways to use this increased access to carbohydrates to our advantage. The rate of evolution leading to changes in the copy number of the amylase gene was about 10,000 times faster than that of single DNA base pair changes in the human genome.

(Related: Do you love corn? Thanks to crossbreeding.)

“It has long been hypothesized that amylase gene copy number had increased in Europeans since the beginning of agriculture, but we have never been able to fully sequence this locus before. It is extremely repetitive and complex,” Sudmant said. “Now, we can finally fully capture these structurally complex regions and, with that, investigate the history of region selection, timing of evolution, and diversity in populations around the world. Now, we can start to think about associations with human diseases.”

One such suspected association is tooth decay. Some previous research suggests that having more copies of AMY1 is associated with more cavities. This could be because saliva is better at converting starch from chewed food into sugar, which feeds the bacteria that eat away at your teeth.

Long read sequencing

The study also took advantage of a genetic sequencing process called long-read sequencing, which allows scientists to read DNA sequences thousands of base pairs in length to precisely capture where repetitive stretches are located.

At the time of the study, the Human Pangenome Reference Consortium (HPRC) had collected long-read sequences from 94 human haploid genomes. The team used these genomes to assess the variety of contemporary amylase regions. They then assessed that same region in 519 ancient European genomes. Using the HPRC genomes, called pangenomes, provided a more inclusive reference that more accurately captures human diversity.

Joana Rocha, a co-author of the study and a postdoctoral fellow at UC Berkeley, compared the region where the amylase genes are clustered to “sculptures made of different Lego pieces. Those are the haplotype structures. In previous work, you had to first take apart the sculpture and deduce from a pile of Lego pieces what it might have looked like. Long-read sequencing and pan-genomic methods now allow us to directly examine the sculpture and thus give us unprecedented power to study the evolutionary history and selective impact of different haplotype structures.”

(Related: The last missing piece of the human genome has been deciphered.)

Scientists can use long-read sequencing to explore other areas of the genome, including those related to our immune system, skin pigmentation and mucus production. All of these areas have experienced rapid genetic duplication in recent human history.

“One of the most interesting things we were able to do here was to analyze modern and ancient genomes to dissect the history of structural evolution at this site,” said study co-author and University of Tennessee Health Science Center computational biologist Erik Garrison in a statement.

These methods can also be applied to other species, particularly those that are often around humans. Dogs, pigs, rats and mice have more copies of the amylase gene than their wilder relatives, so they are likely to make use of our table scraps and garbage.