Tiny fish provides giant insight into how creatures adapt to changing environments

A team  from Indiana University and Dartmouth College has identified genes and regulatory patterns that allow some organisms to alter their body form in response to environmental change.

Understanding how an organism adopts a new function to thrive in changing environments has implications for molecular evolution and many areas of science from climate change to medicine, especially in regeneration and wound healing.

The study, which appears in the journal Molecular Biology and Evolution, provides insight into phenotypic plasticity, a phenomenon that enables organisms to change their observable characteristics in response to their environment.

The researchers examined how the Atlantic killifish modifies its gills to live in freshwater or seawater.

The modifications include activating or deactivating channels that secrete salt. The freshwater gill is fundamentally different from the seawater gill. While some of the structures used to maintain salt balance are already known, the new study sheds light on how the killifish coordinates multiple changes in order for their gills to transition from one form to the other, says co-author Bruce Stanton, a professor of microbiology and immunology at the Geisel School of Medicine at Dartmouth. This response, called phenotypic plasticity, involves structural and functional changes.

''Phenotypic plasticity is an incredibly important ability,'' says lead author Joe Shaw, an associate professor at the School of Public and Environmental Affairs at Indiana University. ''Think in terms of the metamorphosis that butterflies go through, except in this case the shift is triggered by a change in the environment.''

Stanton and Shaw previously observed that killifish are more vulnerable to arsenic during changes in salinity. Killifish living in freshwater or seawater can tolerate arsenic well, but even low levels of arsenic interfere with their plastic response required to survive in the new environment.

Since arsenic prevents killifish from shifting between freshwater and seawater, they reasoned that arsenic could be used to identify which genes orchestrate these changes. Arsenic exposure during salt acclimation revealed many genes that orchestrate the killifish plastic response, and these plasticity-enabling genes are maintained at precise levels.

The results suggest strict regulatory control of these genes may be a general feature of plastic responses in other organisms.

The researchers report that plasticity-enabling genes seem to be organized in unusually simple networks, and that these structures may explain why genes involved in the plasticity response are so precisely controlled.

The researchers wondered what kind of network would cause such tight control -- a complicated one, with lots of outside input, or a simple one, largely insulated from what is going on outside.

''I was betting on complex networks being responsible for fine tuning,'' says co-author Tom Hampton, senior bioinformatics analyst at Geisel, ''but I was wrong.  Our plasticity genes seem to be regulated by fewer genes than you expect by chance. It could be that evolution prunes out excess connections to create the kind of network required for the plasticity response.''

The researchers found that nature selects for these networks depending on how much plasticity is required. Killifish living in stable environments have evolved less precise control over plasticity-enabling genes than those living in the least stable environments.

The results have substantial implications for our understanding of molecular evolution by suggesting that natural selection targets the regulatory networks of genes in addition to individual genes or proteins.

The research team is working on experiments that apply the results to other fields. Stanton, who also is director of the Dartmouth Toxic Metals Superfund Research Program and the Dartmouth Lung Biology Center, says low levels of arsenic in drinking water increase risks for lung disease. His lab team is testing whether low-level arsenic interferes with immune responses. Shaw's team is experimenting with killifish that evolved under different conditions in an effort to better understand species that are adapted to withstand abrupt and more widespread changes in their environment. He hopes such research will help to predict and prepare for the threats of global climate change.