Why is a dolphin not a cat? Despite having a common ancestor, different mammalian species have acquired their unique characteristics by repurposing functional elements through gene regulation, says a study.
“What we have shown is that evolution repurposes things that exist in all species, to make each species unique,” explained Paul Flicek from European Bioinformatics Institute (EMBL-EBI) in Britain.
For the study, the researchers compared gene regulation in liver cells from 20 key species including the naked mole rat, human, Tasmanian devil, dolphin and sei whale.
Study of gene regulation in 20 mammals provides insight into how species diverged millions of years ago;
Methods and tools for genetic analysis of humans and mice adapted to study non-model species, such as whales.
“By looking at gene promoters and enhancers in many different mammals, we demonstrated that species-specific enhancers come from ancient DNA – that evolution captures DNA that has been around for a long time, and uses it for gene regulation in specific tissues,” Flicek added.
Evolution has two ways to turn changes in the genome into differences between species: it can change a protein sequence, or it can change the way promoters or enhancers control that protein’s expression.
In some cases evolution uses both strategies at once, the findings showed.
When amino acid sequences evolve very quickly, important regulation changes occur at the same time, the protein-coding sequence and the corresponding regulatory sequence change synergistically.
“This research has given us new insights into mammalian evolution,” Duncan Odom from Cancer Research UK-Cambridge Institute (CRUK CI), University of Cambridge, noted.
“People spend a lot of time and money trying to understand human biology, so most of the tools we have are designed to study human genomes,” explains Camille Berthelot of EMBL-EBI, who led the computational work. “The reference data we have for the less studied species, like the Sei whale or Tasmanian devil, are nothing like the pored-over datasets we have for the human genome. A lot of what we did involved benchmarking, and making sure the methods and algorithms were fit for this kind of comparison.”
The findings were published in the journal Cell.
Villar, D., et al. (2015) Enhancer evolution across 20 mammalian species. Cell. Published online 29 January 2015; DOI: 10.1016/j.cell.2015.01.006.