A New View on Genetic Variation

“We were working with ants, but it was a bit like discovering that we could create shorter or taller human beings.” Stanford’s Sebastian Alvarado is describing an experiment he and his colleagues at McGill University performed on carpenter ants to determine how environmental (or epigenetic) factors can affect genes to vary traits in organisms.

Alvarado’s tinkering can help us understand how life works. Traits such as height, weight, or susceptibility to disease naturally vary across a population. This variation is often driven by the degree that environmental factors influence the expression of a particular gene.

The team chose Camponotus floridanus ants to tinker with because while they all begin very similarly in the larval stage, social, nutritional, and chemical cues cause some genes to be more active, creating a range of body sizes, each specialized to a different task in the colony—from queen to soldier to smaller worker ant. Worker ants within a colony are extremely genetically similar (about 75% related) when they reach adulthood, so they seemed a good way to test how other factors can affect gene expression.

By increasing the degree of DNA methylation (a biochemical process that controls the expression of certain genes—a bit like a dimmer turning a light up or down) of a gene involved in controlling growth called Egfr, the team was able to create a spectrum of worker ant sizes despite the lack of genetic difference between one ant and the next.

“Basically, what we found was a kind of cascading effect. By modifying the methylation of one particular gene that affects others—in this case the Egfr gene—we could affect all the other genes involved in cellular growth," says Alvarado.

And the team says that this new tool could be applied beyond ants.

“In the case of growth in ants, it was the Egfr gene which was determinant,” says Rajendhran Rajakumar, an author of the study, published last week in Nature Communications. “But for other complex traits, whether they are involved in the growth of cancer cells in humans or fat cells in chickens, what we now know is that once we have discovered, in each case, the key genetic position that is affected by epigenetic factors we can then influence how much or how little of the gene is expressed with potentially very far-reaching results.”

“It’s a discovery that completely changes our understanding of how human variation comes to be,” says co-author Ehab Abouheif. “So many human traits, whether they are intelligence, height, or vulnerability to diseases such as cancer, exist along a continuum. If, as we believe, this epigenetic mechanism applies to a key gene in each area, the change is so enormous that it's hard to even imagine right now how it will influence research in everything from health to cognitive development to farming.”

Image: Mélanie Couture and Dominic Ouellette