Accumulated Mutations Create A Cellular Mosaic In Our Bodies

Your body has about 40 trillion cells, and they all arose from a single fertilized egg. But it turns out the DNA in many of those cells is no longer a perfect clone of that original one.

A study published Thursday in the journal Science shows that our body's cells are a mosaic, with many subtle genetic variations.

It's not news that that our cells pick up mutations as we age. Some skin cells morph into moles. And scientists have previously documented widespread genetic changes in cells in the skin, esophagus and blood.

Tumors start out as mutant cells, as well.

"But no one has really characterized this across many different tissues and across a great amount of individuals," says Keren Yizhak. She took that as a challenge as she started working as a postdoctoral researcher at the Broad Institute at MIT and Harvard.

She and her colleagues tapped into genetic information from about 500 people, cataloging 29 different tissues. They found populations of mutant cells in just about everyone they studied.

"The skin, the lung and the esophagus were the ones where we found the highest amount of mutations," she says.

That makes sense, because those tissues are always renewing themselves and are constantly bombarded with sunlight, in the case of skin, and other potentially damaging agents, like smoke in the lungs.

Doctors are used to finding mutations in diseased tissue, namely tumors. But this discovery is different.

"These are all normal tissues," says Gad Getz, who runs the lab where Yizhak worked. "They are not cancerous."

These tissues are just — you. It turns out you aren't simply a clone of the cells you started with, despite what you may have learned in biology class.

"You're just like a big puzzle, with different pieces with different sizes," Getz says. "All of them are very much similar to your original DNA," but you are actually a mosaic of cells with small variations.

This finding in itself is intriguing. But it also has implications for detecting cancer.

It turns out that many of the mutations that cause these cell populations to proliferate are also involved in cancerous growth. So blood tests being developed to detect early signs of cancer could be fooled by these mutations.

"And the fact that [these mutations] already appear in normal cells means we need to be more cautious about detection of early events of cancer," Yizhak says.

"We need to distinguish between ones that eventually could become cancer and ones that maybe are on a dead end and will never become cancers," Getz adds. "And I don't think we know yet what dictates what path the cells would take."

"I think we have to be very cautious in interpreting the results," says Jinghui Zhang, chair of computational biology at St. Jude Children's Research Hospital. Though many of the mutations in these seemingly healthy cells are also known to contribute to cancer, she agrees with Getz that it's hard to sort out what might be considered pre-cancerous versus mutations that are benign.

Zhang also expected to see this pattern in other tissues that are rapidly growing and replenishing themselves, such as cells in the colon. But in this study, colon cells did not appear to contain many mutant populations.

Yizhak suspects that is the case because the sample of colon cells used in her study didn't contain a lot of the cell types that normally proliferate. The tissue she used was developed for a completely different study — she simply took advantage of this large sample of tissue.

"It's an interesting paper," says Jay Shendure, a Howard Hughes Medical Institute investigator at the University of Washington and scientific director of the Brotman Baty Institute in Seattle. He says it may be a bit unsettling to realize that we're actually made up of a gradually changing mosaic of cells. But it doesn't bother him. "I think we should feel OK about it," he says.

He thinks of these mutations as a record of the changes that we accumulate as we grow from a single fertilized egg into an adult human being.

It turns out that these mutations aren't just scattered across our DNA, but they apparently result in discrete clumps of cells, which crop up — and build up — over time.

"That entire process has been marked by nature in each of us."

And, he says, as the technology for reading our genes improves, it's easy to see where this is all leading. "We're only going to see more and more of this, and we're going to see this at almost every scale imaginable," Shendure says, from the microscopic to the obvious.

It seems were are endlessly complex, endlessly fascinating — and still full of mysteries.

You can contact NPR science correspondent Richard Harris at rharris@npr.org.