Original Syn: Pun Intended

A big tip of the hat to Chemjobber, who recently pointed out a puzzling passage in a NY Times story about chemistry in the origin of life field. You can read the original post at Chemjobber's site for the background, which I'll briefly paraphrase here. John Sutherland and his colleagues in the UK have developed a synthesis of RNA building blocks that might help explain how an early form of life based on RNA instead of DNA, also called the "RNA World", might have come about. News outlets around the world covered the story, as did C&EN. The New York Times's writeup mentions the term "original syn", which the reporter describes as "a chemical operation that can affect a molecule’s handedness". Chemjobber hadn't heard of the term and was curious about its origins (something funny in itself, really, the origin of a term in an origin of life story). Read his post for feedback from Chembark blogger Paul Bracher and the Times reporter, Nicholas Wade. I'm quite a bit late to the party, but Gerald Joyce, a professor at the Scripps Research Institute who was interviewed by the Times for the story, graciously responded to my email about "original syn" last weekend. The phrase is in fact a pun, he says. Here's how he explained it in an email. Original syn "refers to a perverse quirk of RNA chemistry whereby a D-nucleotide in the (preferred) anti conformation at the glycosidic bond is closely mimicked by an L-nucleotide in the syn conformation. This results in inhibition of polymerization of activated D-nucleotides by L-nucleotides, and vice versa. This has been termed "enantiomeric cross-inhibition" and was demonstrated experimentally by Leslie Orgel and me many years ago (Joyce et al., Nature 1984, 310, 602). In a racemic mixture it is a real show-stopper for RNA, leading some to propose that the RNA world was preceded by a "pre-RNA world" that did not suffer this limitation. Alternative, as you have reported, the mirror may have been broken prior to the emergence of replicating RNA, thus avoiding 'original syn'."

Author: Carmen Drahl

Share This Post On