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:
According to this site:
In three papers published back-to-back in Science, they provide the first comprehensive picture of a minimal cell, based on an extensive quantitative study of the biology of the bacterium that causes atypical pneumonia, Mycoplasma pneumoniae. The study uncovers fascinating novelties relevant to bacterial biology and shows that even the simplest of cells is more complex than expected.
A network of research groups at EMBL’s Structural and Computational Biology Unit and CRG’s EMBL-CRG Systems Biology Partnership Unit approached the bacterium at three different levels. One team of scientists described M. pneumoniae‘s transcriptome, identifying all the RNA molecules, or transcripts, produced from its DNA, under various environmental conditions. Another defined all the metabolic reactions that occurred in it, collectively known as its metabolome, under the same conditions. A third team identified every multi-protein complex the bacterium produced, thus characterising its proteome organisation.
“At all three levels, we found M. pneumoniae was more complex than we expected,” says Luis Serrano, co-initiator of the project at EMBL and now head of the Systems Biology Department at CRG.
So in what ways is this minimal cell more complex than expected?
Let’s sketch out the basic events associated with getting a protein across the membrane. We’ll join the story after the gene for this protein has been expressed and an RNA molecule coding the amino acid sequence is synthesized. This RNA is known as messenger RNA (mRNA) and it is ultimately fed into the ribosome where its sequence of nucleotides will be decoded and used to string together a particular sequence of amino acids. (see animation here).
If we are about to explore the signal recognition particle through the telic lens, it might help some people to familiarize themselves with the molecular machine known as the ribosome. So sit back and enjoy the protein synthesis show.
Let me explain some more about the human brain protein that is encoded by the ribosomal S5 protein.
As most of you probably know, DNA is a double-stranded chain of nucleotides. When it is time to express a gene, the RNA polymerase unwinds the DNA and uses only one of the strands to make a copy in the RNA format as shown in the figure below:
What I showed with S5 is that while the bottom strand codes for this highly conserved ribosomal protein, the upper complementary strand, if it were to be transcribed and translated, would code for an unnamed protein product isolated from the human brain.
We have been focused on the ribosome as one plausible vehicle for front-loading evolution. This hypothesis led us to successfully expect ribosomal proteins would carry out additional functions and that some portions of the ribosomal RNA might actually code for protein. So it’s time to dig a little deeper.
I recently noted that the small ribosomal subunit protein, S5, also moonlights in the differentiation of red blood cells. One thing that is striking about S5 is its highly conserved amino acid sequence.
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.