For years, I have used the hypothesis of front-loading to argue that multifunctional, moonlighting proteins would be expected to exist. I explained the logic and provided many examples using the ribosome as a candidate of such front-loading. In fact, as far as I know, I’m the only one to note that the gene for the ribosomal protein s5 also seems to code for a protein that is expressed in the mammalian brain (see here and here).
A fresh new study has just been published that fits seamlessly with the above essays:
With the emergence of the nucleus as part of the eukaryotic cell plan comes the decoupling of transcription and translation. But something else is decoupled – the two processes that control the levels of messenger RNA in the cell. These two processes are mRNA synthesis, which occurs within the nucleus, and mRNA decay, which occurs in the cytoplasm. By physically separating the two processes, you run into a potential control problem where an increase in the synthesis of mRNA, for example, might not translate as an increase in mRNA levels because elevated mRNA decay rates in the cytoplasm might cancel out any increase in synthesis rates. And given that mRNA levels play important roles in embryological development, this could pose a serious problem for the evolutionary emergence of metazoa.
So is there a way to keep mRNA synthesis and decay rates coupled while allowing for the enhanced compartmentalization of the eukaryotic cells? Consider some recent research findings.
The logic of front-loading allowed me to hypothesize that ribosomal proteins would moonlight. Admittedly, it is more like an expectation than a precise prediction, but what matters is that the hypothesis directed my attention with subsequent payoff. After determining that about 2/3 of the universal SSU ribosomal proteins appear to moonlight, the criterion of Rationality kicks in. That is, if it is possible to front-load alternative functions into ribosomal proteins, a good designer would attempt to maximally exploit this particular vehicle for front-loading. So if the ribosome was front-loaded where two out of three ribosomal proteins were preadapted, why not all of them? Using this logic, I then noted we should expect to find moonlighting roles for the other third of the universal SSU ribosomal proteins – s17, s5, s8, s11, and s15 – for which I could not find a potential moonlighting function.
So after writing up my original blog entry on moonlighting ribosomal proteins, I went back to the data bases to search more closely.
While outlining the logic of front-loading in The Design Matrix, I noted how the existence of multifunctional (moonlighting) proteins would serve the needs of front-loading. In essence, a protein with multiple functions can be viewed as a protein that is packed with preadaptations ready to be more fully exploited when the proper conditions arise.
This developing paradigm has allowed me to come up with a prediction. If evolution was front-loaded, and a significant aspect of this front-loading existed as multifunctional proteins, whereby secondary or tertiary functions could be unleashed as evolution proceeded into the future, an excellent candidate for storage of some of these secondary functions would be the ribosome, the protein-synthesizing factory of the cell. This is because a designer could count on the ribosome being retained, largely unchanged, throughout billions of years of evolution because it plays such an absolutely essential role in life. If it remains largely unchanged, secondary functions can be carried into the future. Thus, I would predict that ribosomal proteins, which normally function as chaperones to fold the ribosomal RNA and hold it together to form the functioning ribosome, would also exhibit secondary functions (moonlight).
And a survey of the literature does indeed support this prediction.
Recent research has identified a protein that is essential for mitochondrial function:
Cellular respiration depends on proteins synthesised outside the mitochondrion and imported into it, and on proteins synthesised inside the mitochondrion from its own DNA. Researchers at Karolinska Institutet have now shown that a specific gene (Tfb1m) in the cell’s nucleus codes for a protein (TFB1M) that is essential to mitochondrial protein synthesis. If TFB1M is missing, mitochondria are unable to produce any proteins at all and cellular respiration cannot take place.
Sounds like a crucial protein. So what is TFB1M?
The transcription of genes from mitochondrial DNA requires a mitochondrial RNA polymerase (see POLRMT, MIM 601778) and a DNA-binding transcription factor (see TFAM, MIM 600438). Transcription factor B1 (TFB1M) is a part of this transcription complex.[supplied by OMIM]
So it’s an important transcription factor needed to express all the mitochondrial genes.
Is it a recent innovation or does it extend far back into deep time?