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.