Is Ribosome the new 42?

(January 30th, 2015) Some 3.5 billion years ago, the first organisms embraced life on planet earth. A primitive envelope girded a primitive genome to make the simplest living cell. But could a loner genome account for all the complexity of the living cell – survival, sustenance and procreation?

What is the bare minimum needed to build and sustain a living cell? Is it the genes that encode life or the fuel that powers the cell? According to Danish scientists Meredith Root-Bernstein and her father Robert Root-Bernstein, both answers may only be partly correct. Instead, a new solution to life, if not to universe and everything, may in fact be the ribosome.
To disentangle the complexity of life, scientists have traced back evolution and in the past decade, reconstructed trees of life using vast arrays of genetic data. The results foster the idea that all life-forms descended from a universal common ancestor (UCA). UCA is a simple, hypothetical single-cell living entity, of 3.5 billion years ago, capable of most of the basic biological processes of today’s complex living organisms.

As simple as it was, UCA is believed to have been jolted to life from a bunch of chemical molecules. For the believers of the ‘RNA-first’ theory, this was a self-copying piece of RNA – the primitive genome – that encoded life, while for those who profess a ‘metabolism-first’ model, it was a set of proteins that laid the cell’s architecture and fuelled it. But neither RNA nor proteins can independently explain how simple replicable molecules evolved into complex cells with organised sub-structures capable of driving life. A new study by the father-daughter duo suggests that the ribosome could have been the best intermediate in the evolutionary jump from RNA to a cell.

Ribosomes consist of three types of ribosomal RNA (rRNA) – 23S, 16S and 5S in bacteria – and ribosomal proteins. They are thought to serve a rather limited role of spewing out proteins but the fact that they contain both RNA and proteins make them the likely missing link between RNA and the cell. Meredith explains: “To fill the gap, primitive ribosomes would have to be able to carry out a number of functions that are not currently attributed to them. Most importantly, these primitive ribosomes would have to be able to replicate themselves – and that means not just their RNA, but also their proteins. A self-replicating ribosome becomes something significantly more complicated than a gene, yet significantly simpler than a cell and thus a perfect missing link.”

If primitive ribosomes were self-replicating, they had to be able to autonomously copy their RNA and make their own proteins. This could be possible only if the components of transcription and translation were all encoded within the rRNAs. Further, the remnants of such coding should still reside in the ribosomes of present-day organisms. Meredith and Robert Root-Bernstein began their hunt for these ‘living fossils’ in the rRNA of an E.coli strain. In addition to rRNA, protein translation also requires mRNA and twenty tRNA – one for each amino acid. The duo found traces of E.coli tRNA and mRNA sequences in the bacterial rRNAs suggesting that vestiges of translation are embedded in these rRNAs. All twenty tRNAs share 50-70% sequence identity with the rRNAs. The tRNAs are encoded either directly in the 16S rRNA, in which case they could be generated by simply cutting the rRNA, or indirectly in a complementary sequence in the 23S rRNA. Many of these remnant stretches even seemed capable of folding into the correct 3D structure for tRNAs – a feature crucial to tRNA function – when the sequences were modelled in 3D using a structure design algorithm.

What’s more, the team found evidence of a very minimal toolbox of proteins in the rRNAs when they aligned mRNA sequences of ‘ribosome-related’ proteins with the rRNA sequences. Gene sequences encoding for enzymes, which load tRNAs with amino acids before translation, transcriptional and translational proteins, as well as for proteins, which make ATP, are all encrypted within the rRNAs. The mRNA and rRNA sequences matched by at least 50% and much of the similarity, where functional data was available, was found within regions that make ‘active sites’. “The existence of this information means that we have to rethink the divisions we make between messenger RNA, transfer RNA and ribosomal RNA – at one time, we propose, they were all integrated into the same molecule,” Meredith says.

Their study lends a new perspective to the origin of cells. Unlike the ‘genes-first’ and ‘metabolism-first’ theories, theirs suggests that genes and metabolism co-evolved in a primitive ribosome that could efficiently self-replicate. As Meredith explains: “Looking backwards, we are hypothesising that the RNA subunits that evolved into ribosomes would have encoded protein subunits, to which they would also have bound, thereby producing stable, functional RNA-protein structures. These functional RNA-protein structures would have been integrated later to form the ribosome. Looking forwards, we have predicted that if ribosomal RNA encodes the tRNAs and proteins necessary to carry out its own replication, then these ribosomal RNA ‘genes’ would have formed the basis of the cellular genome as well. In other words, there should be a lot more ribosome-related genes in the genome than are necessary merely to encode the ribosome itself.”

Though the study makes a more convincing claim about the origin of life than previous theories, it is restricted by a lack of resources, for instance, of functional information, which was available only for a fraction of the proteins. Besides, sequence similarities do not necessarily mean that primordial rRNAs actively played the roles of mRNAs and tRNAs. “Demonstrating our hypothesis will require a great deal of work. Our current study focuses mainly on the ribosomal RNA of E. coli K12… this work obviously needs to be done in detail. We would like to explore whether the protein subunits encoded by ribosomal RNA contain residual ribosomal functions and whether the transfer RNAs encoded by the ribosomal RNA can function as tRNAs,” says Meredith.

Madhuvanthi Kannan

Image: Chandra Bajaj, Institute for Computational Engineering and Sciences, University Texas

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