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Understanding the constraints of evolution provides roadmap to mammalian biology

Date:
October 12, 2011
Source:
Baylor College of Medicine
Summary:
Researchers produced a high-resolution genomic map of more than 3.5 million constrained elements that account for approximately four percent of the human genome. The researchers identified 3,788 candidate new exons with more than half of those existing outside of known protein-coding genes. They found possible functions for about 60 percent of the chemicals that make up DNA but the functional class of the remaining 40 percent remains unknown.

In the world of mammals, the two-toed sloth and armadillo appear exceedingly different from humans and their primate cousins.

Science, however, recognizes that certain elements remain constant, and in genomic terms, those things that remain the same are very important to survival. Comparing the genomes of 29 mammals -- from humans and primates to the two-toed sloth -- provides new understanding of the development of species and the importance of what has remained the same and what has changed during evolution, said an international consortium of genomics experts including those in the Human Genome Sequencing Center at Baylor College of Medicine.

The project led by the Broad Institute of Harvard and the Massachusetts Institute of Technology in Cambridge, Massachusetts, involved bioinformatics, laboratory and genomic experts from the United States and Europe. In a report that appears online in the journal Nature, the researchers produced a high-resolution genomic map of more than 3.5 million constrained elements that account for approximately 4 percent of the human genome. The researchers identified 3,788 candidate new exons (the genetic information for parts of proteins) with more than half of those existing outside of known protein-coding genes. They found possible functions for about 60 percent of the constrained bases (the chemicals that make up DNA) but the functional class of the remaining 40 percent remains a mystery.

The high experimental resolution enabled a detailed description of those elements that have remained the same over the last one hundred million years.

"Evolutionary constraint refers to those things that don't change from one species to the next," said Dr. Kim Worley, associate professor in the Human Genome Sequencing Center at BCM and an author of the report.

"We know about most protein coding genes," said Worley. "We know about exons (the parts of the genome that make up the blueprint for making proteins) and we know a little about the functions of the non-coding regions. There are all sorts of regulatory elements in the genome that we don't have a handle on yet."

"Twenty years ago, much of this was called 'junk DNA,'" she said. Now that so-called junk is being recognized as the fine-tuning elements that keep gene levels on track and determine which genes work in which tissues and at what times in one's lifetime.

"I'm excited to take this new information and go back and look at the data from human projects involving cancer or Mendelian (genetic) diseases," she said. "We can look at the protein coding sequences and the non-protein coding regulatory elements that don't change across these different species and we will likely find disease-causing changes in humans that we didn't know existed.

Mammals sequenced include: human, chimpanzee, rhesus macaque, tarsier, mouse lemur, bush baby, tree shrew, mouse, rat, kangaroo rat, guinea pig, squirrel, thirteen-lined ground, rabbit, pika, alpaca, dolphin, bottlenosed, cow, horse, domestic cat, domestic dog, little brown bat, fruit bat, European hedgehog, common shrew, African elephant, hyrax, rock, tenrec, nine-banded armadillo, and the two-toed sloth.

Other major institutions involved in this research include the Genome Institute at Washington University in St. Louis, Mo.; Uppsala University in Sweden; the MIT Computer Science and Artificial Intelligence Laboratory in Cambridge, MA; University of Copenhagen in Denmark; the Wellcome Trust Genome Campus in Hinxton, U.K.; University of California, Santa Cruz; Stanford University in California; the Howard Hughes Medical Institute; Gladstone Institutes at the University of California, San Francisco; Harvard University in Cambridge, Mass.; Cornell University in Ithaca, N.Y.; the Research Institute of Molecular Pathology in Vienna, Austria; the Genome Informatics Section, NISC Comparative Sequencing Program, Genome Technology Branch and NIH Intramural Sequencing Center of the National Human Genome Research Institute in Bethesda, Md.; and Aarhus University Hospital in Skejby, Denmark.

Other BCM researchers who took part in this study include: Christie L. Kovar, Donna M. Muzny, Dr. Richard A. Gibbs, Dr. Andrew Cree, Huyen H. Dihn, Dr. Gerald Fowler, Shalili Jhangiani, Vandita Joshi, Sandra Lee, Lora R. Lewis, Lynne V. Nazareth, Geoffrey Okwuonu and Jireh Santibanez.

Funding for this work came from the National Human Genome Research Institute; the National Institute for General Medicine; the European Science Foundation; the National Science Foundation; the Sloan Foundation; an Erwin Schrödinger Fellowship of the Austrian Fonds zur Förderung der Wissenschaftlichen Forschung; the Gates Cambridge Trust; Novo Nordisk Foundation; a Statistics Network Fellowship from the department of mathematical sciences at the University of Copenhagen; the David and Lucile Packard Foundation; the Danish Council for Independent Research | Medical Sciences and The Lundbeck Foundation.


Story Source:

The above story is based on materials provided by Baylor College of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Kerstin Lindblad-Toh, Manuel Garber, Or Zuk, Michael F. Lin, Brian J. Parker, Stefan Washietl, Pouya Kheradpour, Jason Ernst, Gregory Jordan, Evan Mauceli, Lucas D. Ward, Craig B. Lowe, Alisha K. Holloway, Michele Clamp, Sante Gnerre, Jessica Alföldi, Kathryn Beal, Jean Chang, Hiram Clawson, James Cuff, Federica Di Palma, Stephen Fitzgerald, Paul Flicek, Mitchell Guttman, Melissa J. Hubisz, David B. Jaffe, Irwin Jungreis, W. James Kent, Dennis Kostka, Marcia Lara, Andre L. Martins, Tim Massingham, Ida Moltke, Brian J. Raney, Matthew D. Rasmussen, Jim Robinson, Alexander Stark, Albert J. Vilella, Jiayu Wen, Xiaohui Xie, Michael C. Zody, Jen Baldwin, Toby Bloom, Chee Whye Chin, Dave Heiman, Robert Nicol, Chad Nusbaum, Sarah Young, Jane Wilkinson, Kim C. Worley, Christie L. Kovar, Donna M. Muzny, Richard A. Gibbs, Andrew Cree, Huyen H. Dihn, Gerald Fowler, Shalili Jhangiani, Vandita Joshi, Sandra Lee, Lora R. Lewis, Lynne V. Nazareth, Geoffrey Okwuonu, Jireh Santibanez, Wesley C. Warren, Elaine R. Mardis, George M. Weinstock, Richard K. Wilson, Kim Delehaunty, David Dooling, Catrina Fronik, Lucinda Fulton, Bob Fulton, Tina Graves, Patrick Minx, Erica Sodergren, Ewan Birney, Elliott H. Margulies, Javier Herrero, Eric D. Green, David Haussler, Adam Siepel, Nick Goldman, Katherine S. Pollard, Jakob S. Pedersen, Eric S. Lander, Manolis Kellis. A high-resolution map of human evolutionary constraint using 29 mammals. Nature, 2011; DOI: 10.1038/nature10530

Cite This Page:

Baylor College of Medicine. "Understanding the constraints of evolution provides roadmap to mammalian biology." ScienceDaily. ScienceDaily, 12 October 2011. <www.sciencedaily.com/releases/2011/10/111012132647.htm>.
Baylor College of Medicine. (2011, October 12). Understanding the constraints of evolution provides roadmap to mammalian biology. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2011/10/111012132647.htm
Baylor College of Medicine. "Understanding the constraints of evolution provides roadmap to mammalian biology." ScienceDaily. www.sciencedaily.com/releases/2011/10/111012132647.htm (accessed July 25, 2014).

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