PHILADELPHIA – By comparing two species of ants, Shelley Berger, PhD, the Daniel S. Och University Professor at the University of Pennsylvania, and colleagues Danny Reinberg, PhD, New York University, and Juergen Liebig, PhD, Arizona State University, have established an important new avenue of research for epigenetics — the study of how the expression or suppression of particular genes affects an organism’s characteristics, development, and even behavior.
Ants, the new model system used in this study, organize themselves into caste-based societies in which most of the individuals are sterile females, limited to highly specialized roles such as workers and soldiers. Only one queen and the relatively small contingent of male ants are fertile and able to reproduce. Yet despite such extreme differences in behavior and physical form, all females within the colony appear to be genetically identical.
Berger, who directs Penn’s Epigenetics program, and colleagues believe that epigenetic mechanisms – chemical modifications to DNA and its supporting proteins that affect gene expression — may be critical in establishing such broad variations in behavior and morphology that arise in individuals, despite having the same genome.
In a study published in Science this week, Berger, her Penn colleagues, and a diverse international team of collaborators including ant biologists, geneticists, and biochemists from Arizona State, NYU, Howard Hughes Medical Institute, and the Chinese Academy of Sciences, showed how differences in gene expression between two ant species, the Florida carpenter ant (Camponotus floridanus) and Jerdon’s jumping ant (Harpegnathos saltator), correlate with separate castes in each.
Sequencing the genomes of each species for the first time, the team also used RNA sequencing to study what Berger calls “the question of whether the differences between female workers and female queens is mostly epigenetic rather than genetic.”
The two species were chosen for comparison because of their marked differences in behavioral structure. “Harpegnathos is more primitive and Camponotus is more advanced in terms of social organization,” explains Berger. “Camponotus has different worker castes that specialize their behavior and Harpegnathos has only one worker caste, but those workers have plasticity in their fertility.” When a Harpegnathos queen dies, other worker ants can actually transform and take over her role, preserving the colony, while the death of a Camponotus queen means the end of that particular colony. The group believes that comparing the flexibility of the less specialized, less advanced Harpegnathos with the more rigid, specialized Camponotus will provide a way of determining whether such changes are controlled by epigenetic modifications.
Citing entomologist E. O. Wilson’s observation that an ant colony can be viewed as a single “superorganism,” Berger compares the different castes of species to human cell differentiation, the processes that determine whether an embryonic stem cell ultimately becomes, for example, a liver cell rather than a neuron in the brain. “It’s these epigenetic changes that are regulating, in part, all of these different cell types in our bodies. The ants — the different castes — are the same genome, so there must be epigenetic regulation. ”
Within that genome, the researchers found all of the gene families that correspond to major epigenetic regulators in mammals. “This makes ants an excellent model for studying epigenetic regulatory mechanisms,” says Berger.
Co-author Reinberg studied the ants’ DNA methylation levels — a key epigenetic mechanism that changes DNA expression — and found that the more primitive Harpegnathos has lower levels of DNA methylation than the more advanced Camponotus. Studying the ant genomes, the research team also found genes corresponding to enzymes that chemically modify histones, the spool-like proteins around which the DNA winds. Modification of histones is another key epigenetic mechanism. The enzymes that were found coded in the ant genomes included histone acetyltransferases (HATs) and deacetylases (HDACs).
Another important question the researchers examined is how such epigenetic changes are activated to produce behavioral or structural changes in ants, such as the transformation of a Harpegnathos worker into a functional queen. Ants communicate by complex chemical signals based on touch and smell that trigger particular responses. The researchers identified differences among the ant castes in the expression of genes that may code for these communication functions.
Epigenetic factors also appear to play a significant role in longevity and aging, another major research focus of Berger’s research group at Penn. She notes, “This division of existence into worker versus queen, in which workers carry out all the activities of the colony whereas the queen is strictly reproductive, apparently allows the queen to live longer than the workers by a substantial amount, up to tenfold in some species.” Queens may also live even a hundred times longer than males.
Indeed, the genomic analysis in one of the species found higher expression levels of telomerase enzymes, which counteract cell aging, in the queens relative to the workers — potentially explaining the increased longevity of the queens.
In the near term, the team plans to work with other research groups to compare the genomes of Harpegnathos and Camponotus to other ant species to reveal how their genomes may underlie profound differences among the species. They will also continue to deeply probe the ant as a model organism for more clues on how epigenetic regulation operates to distinguish the ant castes.
“I think it’s early to claim that we have clear epigenetic changes, but I think we’re certainly headed in that direction,” says Berger. While the work promises intriguing insights into the world of eusocial animals such as ants, ultimately it may also have important implications for human beings.
“Many of the changes that underlie human disease are epigenetic in nature,” Berger points out. “Using very sophisticated models like ants, the more we can understand how epigenetics might regulate these profound changes in physiology, the more we’re going to understand about human development, aging and disease, and ultimately behavior.”
This research was funded by an Howard Hughes Medical Institute Collaborative Innovation Award.
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