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The African coelacanth (cee-la-canth) has captivated people ever since a fisherman caught one off the coast of West Africa in 1938. The fish, which has fins that resemble limbs and dwells in sea caves off the African coast, had been known only through the fossil record and was thought to have gone extinct 70 million years ago. But when the coelacanth was found to be still alive, it presented an opportunity to study the fish’s link to tetrapods – the first land vertebrates.

In a study published online by Nature on Thursday, April 18, 2013, researchers from the Eli and Edythe L. Broad Institute of Harvard University and the Massachusetts Institute of Technology and institutions from around the world show that the coelacanth’s genes are slowly evolving compared to those of other fish and land vertebrates – a finding consistent with the fact that coelacanths today appear almost unchanged from ancestors who lived more than 300 million years ago. Thus coelacanth genes provide a window into the evolution of amphibians and other land animals from marine precursors.

An important part of the study was conducted using a software program called MAKER, which identifies and annotates genes. MAKER was developed by University of Utah human genetics professor Mark Yandell, Ph.D. Two other University of Utah researchers, evolutionary biologist Chris Organ, Ph.D., and Michael S. Campbell, a doctorate student in Yandell’s lab, are co-authors and made important contributions to the study as well. Kerstin Lindblad-Toh, scientific director of the Broad Institute’s vertebrate genome biology group, is the study’s senior author.

Using MAKER’s gene annotations, in conjunction with those of a similar program, Ensembl, developed by a European consortium, researchers found that the coelacanth’s genome sheds new light on the evolution of tetrapods in ways ranging from the sense of smell to immunity to pathogens on land to getting rid of nitrogen through urine. They also concluded that closest living relative to tetrapods is another primitive fish, the lungfish, and not the African coelacanth.

“All the science (regarding coelacanth genes) depends on the original gene annotations, so it’s critical that they be as accurate as possible,” Yandell says.” “MAKER and Ensembl complemented each other by verifying the other’s methods for annotating genes. This ensured that everyone involved had access to accurate gene annotations for their own analyses.”
   
As the evolution from water to land occurred, the ability to rid nitrogen waste from land animals became a critical issue. Fish clear nitrogen by excreting ammonia into the water; humans, amphibians and other land animals do that through the urea cycle, which converts ammonia to a compound that is excreted through urine.

Organ detected a molecular signal of natural selection in the urea cycle, enabling him to identify a gene that underwent selection for ridding nitrogen approximately 375 million years ago.

“Physiologists long have known that processing nitrogen was a huge evolutionary hurdle for vertebrates to live on land,” Organ says. “Identifying a single gene that underwent selection many millions of years ago gives us insight into how adaptations work at the molecular level in general and how this critical system evolved in particular.”

Organ has collaborated with Broad Institute investigators on several other projects and became part of the Nature study after some conversations about how the genomes evolve over large timescales.

Yandell became part of this study through prior projects, including a recently published study that annotated the genes of the lamprey eel. Investigators on those other projects are co-authors on Nature study. He and Campbell also are involved in the gibbon genome project. Gibbons are apes found in tropical and subtropical climates of Asia. Lucia Carbone, of the Oregon Health Sciences University, is leading that study, which is currently nearing publication.