For the past decade and a half, the Levine Lab has been looking for genetic explanations to the social behaviour of living organisms. In their paper “The Gene “degrees of kevin bacon” (dokb) Regulates a Social Network Behaviour in Drosophila melanogaster”, published in Nature Communications, they’ve made a huge stride in understanding how group structure is determined at a genetic level.
As far as we know, [we are] the first to identify an actual gene that contributes to this group-level structure.
– Rebecca Rooke, PhD, Lead Author
The research team, based out of the University of Toronto and the University of Toronto Mississauga, has a history of sharing novel findings. Earlier published works have unearthed that the size of the group impacts the behaviour of fruit flies and that detecting the size of the group relies on perceiving odor1. The former leading the playful question “Can flies count?”.
This newly discovered gene “degrees of kevin bacon” (dokb) was found to have a direct influence on the betweenness centrality of two strains of Drosophila melanogaster (fruit flies). “Betweenness centrality” refers to number of shortest paths that travel through an individual in a network. Individuals with high betweenness centrality can loosely be thought of as “gatekeepers” that can modulate the flow of something through the network. In humans, this could be anything from emotions2 to habits3 and disease4.
Example: In the network above, there is a single path through which something can travel from any individual from either side of this network to connect with the other side. Thus, the blue, middle individual has high betweenness centrality. Image from Rooke et al. (2024).
While human social network behaviour has been analysed by sociologists since the 1930s5, looking for genetic factors in the interactions of living organisms is contemporary. It is also something that is much easier to study in fruit flies than in humans directly as the most effective way to make discoveries of this nature is by manipulating the genome.
The gene that we found is not one that had received a lot of attention. It’s a gene that was in the database living there as a number. It has a sequence that encodes a protein [with no conserved domains].
– Joel Levine, PhD, Principal Investigator
The study stemmed from previous findings that Canton-S (CS) and Oregon-R (OR) flies showed disparate levels of betweenness centrality6. Levine Lab determined this using machine vision software to track individual flies and analyze patterns in their interactions.
Dr. Rebecca Rooke and team, under the supervision of Dr. Joel Levine, first attempted to narrow down the chromosome in flies that was likely responsible for their betweenness centrality by using introgression lines, where they tested OR flies that had 1 of their 3 chromosomes replaced with a CS chromosome. The first “aha” moment came when they narrowed it down to the third chromosome. In a series of subsequent mapping experiments using classic genetics approaches, they were able to refine their search to only 71 genes.
The second “aha” happened when they could further reduce those 71 to just two candidate genes. The other 69 were not expressed differently in the brain of either strain of fly. Nplp2 and CG14109 became the prime suspects.
I was really excited by what flies could do. How they responded to their world. How it seemed you could ask all kinds of questions about them, especially from a perspective of genetics, and get really interesting insights that seem to be relevant to other animals.
– Joel Levine, PhD - On starting his lab
After a series experiments employing CRISPR/Cas9 and RNAi, Nplp2 was eliminated as a candidate and CG14109 looked promising. It was when they replaced the OR CG14109 gene with the CS version and vice versa that CG14109 was confirmed to be the gene responsible. They named it “degrees of kevin bacon” (dokb) after the popular parlour game from the 1990s. The premise being that anyone in the entertainment industry can be connected to the famed actor Kevin Bacon in six steps or less.
The discovery of dokb is the first of its kind in genetic studies of group behaviour. While it is certainly not the only determining factor in the group behaviour of fruit flies, we now know that it is actively involved. Fruit flies share a similar genetic make-up to humans and other living organisms, meaning that further research could give us a much deeper understanding of how we form packs, pods and cliques.
Levine Labs’ dokb findings mark the start of a new and exciting pathway that behavioural research can set out upon. In no small part, thanks to taking a different approach to their studies and keeping an open mind.
Often, researchers would look at a focal individual within a group and then characterize that focal individual and the effects that others had on that individual. The social network approach is unique in that you're looking at all the individuals - as a group, not just focusing on one - and asking, ‘How does the group change?’ What is the group doing and how does that compare to others?
– Rebecca Rooke, PhD, Lead Author
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