One of the evolutionarily oldest enzyme classes is aaRS (for amino acyl tRNA synthetase). Every cell has them including bacteria. Life as we know it wouldn’t exist without them. Briefly they load tRNA with the appropriate amino acid. If this Greek to you, look at the first 3 articles in https://luysii.wordpress.com/category/molecular-biology-survival-guide/.
Amino acyl tRNA syntheses are enzymes of exquisite specificity, having to correctly match up 20 amino acids to some 61 different types of tRNAs. Mistakes in the selection of the correct amino acid occurs every 1/10,000 to 1/100,000, and in the selection of the correct tRNA every 1/1,000,000. The lower tRNA error rate is due to the fact that tRNAs are much larger than amino acids, and so more contacts between enzyme and tRNA are possible.
As the tree of life was ascended from bacteria over billions of years, 13 new protein domains which have no obvious association with aminoacylation have been added to AARS genes. More importantly, the additions have been maintained over the course of evolution (with no change in the primary function of the synthetase). Some of the new domains are appended to each of several synthetases, while others are specific to a single synthetase. The fact that they’ve been retained implies they are doing something that natural selection wants (teleology inevitably raises its ugly head with any serious discussion of molecular biology or cellular physiology — it’s impossible to avoid).
[ Science vol.345 pp 328 - 332 '14 ] looked at what mRNAs some 37 different AARS genes were transcribed into. Six different human tissues were studied this way. Amazingly, 79% of the 66 in-frame splice variants removed or disrupted the aaRS catalytic domain. . The AARS for histidine had 8 inframe splice variants all of which removed the catalytic domain. 60/70 variants losing the catalytic domain (they call these catalytic nulls) retained at least one of the 13 added domains in higher eukaryotes. Some of the transcripts were tissue specific (e.g. present in some of the 6 tissues but not all).
Recent work has shown roles for specific AARSs in a variety of pathways — blood vessel formation, inflammation, immune response, apoptosis, tumor formation, p53 signaling. The process of producing a completely different function for a molecule is called exaptation — to contrast it with adaptation.
Up to now, when a given protein was found to have enzymatic activity, the book on what that protein did was closed (with the exception of the small GTPases). End of story. Yet here we have cells spending the metabolic energy to make an enzymatically dead protein (aaRSs are big — the one for alanine has nearly 1,000 amino acids). Teleology screams — what is it used for? It must be used for something! This is exactly where chemistry is silent. It can explain the incredible selectivity and sensitivity of the enzyme but not what it is ‘for’. We have crossed the Cartesian dualism between flesh and spirit.
Could this sort of thing be the tip of the iceberg? We know that splice variants of many proteins are common. Could other enzymes whose function was essentially settled once substrates were found, be doing the same thing? We may have only 20,000 or so protein coding genes, but 40,000, 60,000, . . . or more protein products of them, each with a different biological function.
So aaRSs are very old molecular biological dogs, who’ve been doing new tricks all along. We just weren’t smart enough to see them (’till now).
Novels may have only 7 basic plots, but molecular biology continues to surprise and enthrall.