An international team of scientists has pinpointed more than 3 million new gene segments that are highly similar between 29 mammals–suggesting that they’re vital to survival. Many of the genes are found in the so-called “dark matter” of the genome, areas whose function is not fully understood.
The new discovery can help scientists who are combing through lists of possible disease-causing genetic mutations, since it stresses genetic bits of highest importance.
“This data can be used to prioritize which disease mutations should be looked at first,” says Kersten Lindblah-Toh, the Scientific Director of Vertebrate Genome Biology at the Broad Institute of Harvard University and Massachusetts Institute of Technology, and an author on the new study.
Almost every cell in the human body contains the same set of genes–roughly 3 billion letters that spell out the instructions for every possible function the cell might need to carry out. But less than two percent of those letters are the codes for proteins, the molecular machines that carry out work in the cell. Other genes are regulatory–they tell cells where and how to make and use those proteins.
But most of the genome has never been classified as either protein-coding genes, or regulatory genes. It’s been dubbed “dark matter” instead, and scientists have only been able to guess at its role.
Now, by comparing the genomes of 29 mammals, an international team of scientists has made inroads into identifying some of the more important regions of “dark matter.” More than 3 million new gene segments were found to be highly similar between all 29 mammals–a hint that they’re important to survival. Otherwise, over evolutionary history, chances are they would have accumulated different, gradual mutations in each of the mammals.
“If you compare three or four mammals, some genes might be the same just by chance,” says Lindblah-Toh, first author of the new work. “But when you’re looking at 29 mammals, something that’s the same in every single one must have an important functional role.”
At least five percent of the human genome, she says, was found to be conserved across the species. Since 1.5 percent of that is already known to be protein-coding genes, it means that at least 3.5 percent of the genome is made up of regulatory elements. Based on similarity to known regulatory elements, the function can be guessed at in about 60 percent of the new gene sequences, she told TPM Idea Lab.
When researchers scan the genome for genetic mutations that cause disease, they often find many mutations that lie outside the protein-coding genes. But until now, they’ve had no way to know whether those mutations are important or not–unless they want to study the function of every mutation in the lab, a daunting task.
With the new data on which sections of the genome are maintained throughout mammalian evolution, researchers have a way to identify whether a mutation is in an important section of the genome or not.
Next, the researchers plan to expand their comparison to include 150 to 200 mammals.
“These first 29 mammals took six years to sequence and compare,” Lindblah-Toh told TPM Idea Lab. “But sequencing is an order of magnitude faster now. The next hundred might take only about six months to sequence and a year to analyze.”
With the additional data, researchers can begin to tackle another question: What makes humans human?
Since the protein-coding part of the genome is highly similar between different species, it’s likely that the differences lie in the regulatory sections.
The current study, Lindblah-Toh says, is too small to make conclusions about what regulatory sections might be uniquely human, but additional genomes will start to tell the story.
