Blogging the Human Genome: DNA palindromes and the troubling future of men. - Slate Magazine

Blogging the Human Genome: DNA palindromes and the troubling future of men. - Slate Magazine

This palindromic fix is ingenious. Too clever, in fact, by half. The system Y uses to compare palindromes regrettably doesn’t “know” which palindrome has mutated and which hasn’t—it just knows there’s a difference. So not infrequently, Y overwrites a good gene with a bad one. The process also tends to—whoops!—accidentally delete the DNA between the palindromes. These mistakes rarely kill a man, but can render his sperm impotent. Overall the Y chromosome might well disappear if it couldn’t correct mutations in this way. But the very process that allows it to make these corrections—its palindromes—can also unman it.

Y, however, loves palindromes: because if Y folds over and makes a giant hairpin of itself, it can bring any two of its palindromes—which are the same genes, one running forward, one backward—into contact. This allows Y to check for mutations and (using a process called gene conversion) copy and paste the good DNA from one location over the bad DNA from the other location. It’s like writing down “A man, a plan, a cat, a ham, a yak, a yam, a hat, a canal: Panama!” on a piece of paper, folding the paper over, and correcting any discrepancies letter by letter—something that happens an average of 600 times in every newborn male.

So whenever malignant DNA arose on Y in the past, cells essentially chopped that DNA out and threw it away. This in turn whittled Y down generation by generation. Once a proud chromosome, home to 1400 genes, Y has been reduced to a stub, with just two dozen or so genes today. And some biologists have predicted that Ys will keep getting chopped down and eventually disappear—perhaps making males disappear with them, since the Y houses the DNA needed to make male gonads.

XX females can mend all their chromosomes this way, including both Xs. But in males, crossing over can’t eliminate any bum Y-chromosome DNA because the Y in XY males lacks a partner to trade with: If any mutations pop up, they’re stuck there.

crossing over also helps nature eliminate bad DNA. Imagine two chromosomes, each with one terrible, deadly mutation in a different gene. If they swap segments of DNA just right, both of the bad genes can end up on one chromosome. That chromosome effectively gets sacrificed and disappears (because any embryo that gets it would die), but at least the other chromosome can live on.

Palindromes have played an important role in evolution. Many bacteria like to shred each other’s DNA with special wire-cutter enzymes that happen to lock onto palindromes and start snipping. As a result, microbes have learned the hard way to avoid even modest palindromes. Not that we higher creatures tolerate many palindromes either. Consider CTAGCTAG and GATCGATC again. Notice that the first letter within each string can pair-bond with the last (C...G), the second with the penult (T...A), and so on. So if the DNA strand on one side ever disengaged and buckled upward, a kink (or “hairpin”) can form.

These hairpins can kill a cell by making DNA impossible to copy or transcribe.

Most DNA genes manufacture proteins—that’s their purpose. And although DNA strands can run for millions upon millions of letters, the functional units of DNA are mere triplets, like AAC, or GTA. To make proteins, cells first “transcribe” a DNA triplet into a triplet of RNA, a closely related molecule. They then “translate” each RNA triplet into an amino acid, the building blocks of proteins. Overall, with four DNA letters, there are 64 possible unique triplets (4 x 4 x 4 = 64). That means cells could, in theory, code for up to 64 different amino acids, by assigning one triplet to each amino acid. In reality, cells use only 20 amino acids, so two or more triplets often get assigned to the same amino acid. AAA and AAG both code for the amino acid lysine, for example. This redundancy makes AAA and AAG genetic synonyms.