Frameshift

Pierre had searched long and hard for an area to specialize in. His first instinct had been to do research directly into Huntington’s disease, but ever since the Huntington’s gene had been discovered, many scientists were concentrating on that. Naturally, Pierre hoped they would find a cure — and soon enough to help him, of course, if it turned out that he himself did have the disease. But Pierre also knew of the need for objectivity in science: he couldn’t afford to piss away what time he might have left chasing slim leads that would probably amount to nothing-leads that someone without Huntington’s would know enough to abandon, but that he, out of desperation, might devote far too much time to.

Pierre decided instead to concentrate on an area most other geneticists were by and large ignoring, in hopes that such territory would be more likely to yield a breakthrough that might indeed get him a Nobel Prize. He centered his research on the so-called junk DNA, or introns: the 90 percent of the human genome that did not code for protein synthesis.

Exactly what all that DNA did do no one was quite sure. Some parts seemed to be foreign sequences from viruses that had invaded the genome in the past; others were endlessly stuttering repeats — ironically, similar in structure to the very unusual gene that caused Huntington’s; others still were deactivated leftovers from our evolutionary past. Most geneticists felt the Human Genome Project could be completed much more quickly if the junk nine-tenths were simply ignored. But Pierre harbored the suspicion that there was something significant coded in some as yet undeciphered way into that mess of nucleotides.

His new research assistant, a UCB grad student named Shari Cohen, did not agree.

Shari was tiny and always immaculately dressed, a porcelain doll with pale skin and lustrous black hair — and a giant diamond engagement ring.

“Any luck at the library?” asked Pierre.

She shook her head. “No, and I’ve got to say this seems like a long shot, Pierre.” She spoke with a Brooklyn accent. “After all, the genetic code is simple and well understood.”

And so, indeed, it seemed to be. Four bases made up the rungs of the DNA ladder: adenine, cytosine, guanine, and thymine. Each of those was a letter in the genetic alphabet. In fact, they were usually referred to simply by their initial letters: A, C, G, and T. Those letters combined together to form the three-letter words of the genetic language.

“Well,” said Pierre, “consider this: the genetic alphabet has four letters, and all its words are three letters long. So, how many possible words does the genetic language have?”

“Four to the third,” said Shari, “which is sixty-four.”

“Right,” said Pierre. “Now, what do these sixty-four words actually do?”

“They specify the amino acids to be used in protein synthesis,” replied Shari. “The word AAA specifies lysine, AAC specifies asparagine, and so on.”

Pierre nodded. “And how many different amino acids are used in making proteins?”

“Twenty.”

“But you said there are sixty-four words in the genetic vocabulary.”

“Well, three of the words are punctuation marks.”

“But even taking those into account, that still leaves sixty-one words to express only twenty concepts.” He moved across the room and pointed to a wall chart labeled “The Genetic Code.”

Shari came over to stand next to him. “Well, just as in English, the genetic language has synonyms.” She pointed at the first box on the chart.

“GCA, GCC, GCG, and GCT all specify the same amino acid, alanine.”

“Right. But why do these synonyms exist? Why not just use twenty words, one for each amino?”

Shari shrugged. “It’s probably a safety mechanism, to reduce the likelihood of transcription errors garbling the message.”

Pierre waved at the chart. “But some aminos can be specified by as many as six different words, and others by only one. If synonyms protected against transcription errors, surely you’d want some for every word.

Indeed, if you were designing a sixty-four-word code simply for redundancy, you might devote three words apiece to each of the twenty amino acids, and use the four remaining words for punctuation marks.”

Shari shrugged. “I guess. But the DNA system wasn’t designed; it evolved.”

“True, true. Still, nature tends to come up with optimized solutions through trial and error. Like the double helix itself — remember how Crick and Watson knew they’d found the answer to how DNA was put together?

It wasn’t because their version was the only possible one. Rather, it was because it was the most beautiful one. Why would some aspects of DNA be absolutely elegant, while others, including something as important as the actual genetic code, be sloppy? My bet is that God or nature, or whatever it was that put DNA together, is not sloppy.”

“Meaning?” said Shari.

“Meaning maybe the choice of which synonym is used when specifying an amino acid actually encodes additional information.”