Genome news flash: We’re all a little bit broken

We’ve all had cars with a bunch of broken parts that get us where we want to go for years with no obvious problem. Does the human genome have the same tolerance for permanent damage?

The answer is: Sure.

A new study estimates that the average person goes through life with 20 genes permanently out of commission. With each of us possessing about 20,000 genes, that means 0.1 percent of our endowment is broken from the start — and we don’t even know it.

Whether being born with 20 broken genes is horrifying (“Get me customer service!”) or reassuring (“Whew, only 20!”) depends on one’s expectation of perfection.

“It does suggest that human beings have a bigger tolerance for mutation than we thought,” said Daniel G. MacArthur of the Wellcome Trust Sanger Institute in England, who led the study published Thursday in the journal Science. “That we can actually have 20 genes knocked out and still be walking around without suffering any ill effects — that was surprising.”

Mark Gerstein of Yale University, one of the 50 scientists around the world who assisted him, agreed: “This is a testament to how robust people are.”

Which genes are inactivated differs from person to person. Across the entire species, however, at least 250 of them — and probably a lot more — are expendable. They’re not part of the essential tool kit for making and running a human being.

As one might expect, genes that can go missing without being missed aren’t involved in essential functions. They control things that are nice to have (like a certain smell receptor) but aren’t required for survival (like an enzyme in a basic metabolic pathway). They’re the radio and door lock, not the drive shaft and brake pedal.

The point of the research, however, goes far beyond a Rorschach test of self-image. It’s the latest deep-dive into the human genome, our species’s 3-billion-letter instruction manual for self.

The normal function of many of the “expendable” genes isn’t known. They’re simply recognized as broken because of certain molecular signatures in the sequence of their nucleotides (“letters”) or other detectable abnormalities.

However, by determining which genes can be tolerated in that state — and labeling what their molecular damage consists of — the researchers are building a reference book that will prove useful to other scientists trying to learn the function of all the human genes. It will help especially in determining whether newly discovered mutations are likely to cause disease or are probably “benign.”

As biologists come to understand better how genes interact with one another in complex networks, they may be able to discover how much of what makes each of us unique is a product of what we lack, and not just what we have.

What the researchers did in the new study is carefully read a book — an individual’s genome — in which some of the sentences — a single gene — have suffered a typographical catastrophe. Words have been changed, their order changed, or whole phrases have been dropped. Whatever the cause, the result is a sentence that no longer makes sense. In genetic terms, these are “loss-of-function variants.”