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Mindboggling result of Ribosomal RNA sequence analysis

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Mindboggling result of Ribosomal RNA sequence analysis
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RumraketUser avatarPosts: 956Joined: Fri Jun 25, 2010 7:49 am Gender: Male

Post Mindboggling result of Ribosomal RNA sequence analysis

So I recently read a paper reporting what is possibly the most incredible and unexpected results into the study of the nature of the ribosome. It turns out the ribosome contains nucleotide sequences of all 20 tRNA molecules, several ribosomal proteins, RNA polymerases and a host of other entities. The authors speculate the ribosome itself might therefore constitute a vestige of a stage in the RNA world, where it was basically the first self-replicating genome of some kind of RNA based organism.

It is a curious fact to consider, that the ribosome is a large, mostly RNA-based molecular machine that "reads" RNA, as one would expect a putative primordial self-replicating RNA or RNA-polymerase would do. It is even more amazing to consider that this machine, in addition to containing the genes for it's own construction (basically that the genome IS the entity that replicates), also contain the genetic sequences that encodes the tRNA molecules. Seriously, what are the odds of that? Isn't that an amazing and almost unbelievable happenstance? That the ribosome itself contain the sequences for tRNA molecules carrying all 20 amino acids? Even now, 4 billion years removed from when these tRNA genes would have been active.

Even more amazingly, some of the proteins that coat the ribosome and aid it in it's translation of messenger-RNA, are themselves encoded in RNA nucleotide sequence, in the ribosomal RNA.

As if that wasn't enough, additional metabolic and replication-related enzymes and ribozymes are encoded in overlapping readingframes in ribosomal RNA. This literally boggles the mind. By looking at this single molecular machine and analyzing nucleotide sequences in detail, we are quite possibly looking at what used to be almost the entire genome of one of the very first stages of life in the RNA world. I used to think that any knowledge of how that RNA world looked and what kinds of genetic machinery was contained within it, was forever obscured by the erasing nature of the accumulating mutations of time and the gradual replacement and loss of these primordially essential components. Not so.

Additionally and related, two classes of protein enzymes are today involved in the translation system and the biosynthesis of proteins. A step in the translation of proteins involve the covalent linkage of amino acids to the tRNA molecules themselves. This step is catalyzed by the enzymes called aminoacyl-tRNA-synthetases, of which there are two classes (class I and II). Each class is divided into 10 unique enzymes, 20 in total, 10 in each class. Comparative genetics reveal that the 10 enzymes in each class are related to each other, so all 10 enzymes in each class converge on one ancestral aminoacyl-tRNA-synthetase enzyme. An ancestor that gave rise to all 10 enzymes in each class. Now comes the amazing part. The nucleotide sequence that encodes the amino acid sequence of the ancestor to the Class I aminoacyl-tRNA-synthetase, is the antiparallel DNA strand to the nucleotide sequence that encodes the amino acid sequence of the ancestor to the Class II aminoacyl-tRNA-synthetases.

So both classes of aminoacyl-tRNA-synthetases, Class I and II, 20 enzymes in total, was originally encoded by a single gene. The 3'-5' strand encoded the class I synthetase, and the 5'-3' encoded the class II synthetase. Let that fester in your skull for a while.

Read these papers, have your mind blown:
https://www.ncbi.nlm.nih.gov/pubmed/25500179
The ribosome as a missing link in the evolution of life.
Root-Bernstein M, Root-Bernstein R.
Abstract
Many steps in the evolution of cellular life are still mysterious. We suggest that the ribosome may represent one important missing link between compositional (or metabolism-first), RNA-world (or genes-first) and cellular (last universal common ancestor) approaches to the evolution of cells. We present evidence that the entire set of transfer RNAs for all twenty amino acids are encoded in both the 16S and 23S rRNAs of Escherichia coli K12; that nucleotide sequences that could encode key fragments of ribosomal proteins, polymerases, ligases, synthetases, and phosphatases are to be found in each of the six possible reading frames of the 16S and 23S rRNAs; and that every sequence of bases in rRNA has information encoding more than one of these functions in addition to acting as a structural component of the ribosome. Ribosomal RNA, in short, is not just a structural scaffold for proteins, but the vestigial remnant of a primordial genome that may have encoded a self-organizing, self-replicating, auto-catalytic intermediary between macromolecules and cellular life.


https://www.ncbi.nlm.nih.gov/pubmed/26953650
The ribosome as a missing link in prebiotic evolution II: Ribosomes encode ribosomal proteins that bind to common regions of their own mRNAs and rRNAs.
Root-Bernstein R, Root-Bernstein M.
Abstract
We have proposed that the ribosome may represent a missing link between prebiotic chemistries and the first cells. One of the predictions that follows from this hypothesis, which we test here, is that ribosomal RNA (rRNA) must have encoded the proteins necessary for ribosomal function. In other words, the rRNA also functioned pre-biotically as mRNA. Since these ribosome-binding proteins (rb-proteins) must bind to the rRNA, but the rRNA also functioned as mRNA, it follows that rb-proteins should bind to their own mRNA as well. This hypothesis can be contrasted to a "null" hypothesis in which rb-proteins evolved independently of the rRNA sequences and therefore there should be no necessary similarity between the rRNA to which rb-proteins bind and the mRNA that encodes the rb-protein. Five types of evidence reported here support the plausibility of the hypothesis that the mRNA encoding rb-proteins evolved from rRNA: (1) the ubiquity of rb-protein binding to their own mRNAs and autogenous control of their own translation; (2) the higher-than-expected incidence of Arginine-rich modules associated with RNA binding that occurs in rRNA-encoded proteins; (3) the fact that rRNA-binding regions of rb-proteins are homologous to their mRNA binding regions; (4) the higher than expected incidence of rb-protein sequences encoded in rRNA that are of a high degree of homology to their mRNA as compared with a random selection of other proteins; and (5) rRNA in modern prokaryotes and eukaryotes encodes functional proteins. None of these results can be explained by the null hypothesis that assumes independent evolution of rRNA and the mRNAs encoding ribosomal proteins. Also noteworthy is that very few proteins bind their own mRNAs that are not associated with ribosome function. Further tests of the hypothesis are suggested: (1) experimental testing of whether rRNA-encoded proteins bind to rRNA at their coding sites; (2) whether tRNA synthetases, which are also known to bind to their own mRNAs, are encoded by the tRNA sequences themselves; (3) and the prediction that archaeal and prokaryotic (DNA-based) genomes were built around rRNA "genes" so that rRNA-related sequences will be found to make up an unexpectedly high proportion of these genomes.


https://www.ncbi.nlm.nih.gov/pubmed/26088142
Functional Class I and II Amino Acid-activating Enzymes Can Be Coded by Opposite Strands of the Same Gene.
Martinez-Rodriguez L, Erdogan O, Jimenez-Rodriguez M, Gonzalez-Rivera K, Williams T, Li L, Weinreb V, Collier M, Chandrasekaran SN, Ambroggio X, Kuhlman B, Carter CW Jr.
Abstract
Aminoacyl-tRNA synthetases (aaRS) catalyze both chemical steps that translate the universal genetic code. Rodin and Ohno offered an explanation for the existence of two aaRS classes, observing that codons for the most highly conserved Class I active-site residues are anticodons for corresponding Class II active-site residues. They proposed that the two classes arose simultaneously, by translation of opposite strands from the same gene. We have characterized wild-type 46-residue peptides containing ATP-binding sites of Class I and II synthetases and those coded by a gene designed by Rosetta to encode the corresponding peptides on opposite strands. Catalysis by WT and designed peptides is saturable, and the designed peptides are sensitive to active-site residue mutation. All have comparable apparent second-order rate constants 2.9-7.0E-3 M(-1) s(-1) or ∼750,000-1,300,000 times the uncatalyzed rate. The activities of the two complementary peptides demonstrate that the unique information in a gene can have two functional interpretations, one from each complementary strand. The peptides contain phylogenetic signatures of longer, more sophisticated catalysts we call Urzymes and are short enough to bridge the gap between them and simpler uncoded peptides. Thus, they directly substantiate the sense/antisense coding ancestry of Class I and II aaRS. Furthermore, designed 46-mers achieve similar catalytic proficiency to wild-type 46-mers by significant increases in both kcat and Km values, supporting suggestions that the earliest peptide catalysts activated ATP for biosynthetic purposes.


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"Nullius in verba" - Take nobody's word for it. https://en.wikipedia.org/wiki/Nullius_in_verba
Extraordinary claims require extraordinary evidence.
Sat Mar 11, 2017 4:55 pm
Nesslig20User avatarPosts: 189Joined: Wed Mar 16, 2016 6:44 pm Gender: Male

Post Re: Mindboggling result of Ribosomal RNA sequence analysis

Truly amazing! I have seen other papers about the evolution of Ribosomes too. They are always fascinating to read.

History of the ribosome and the origin of translation
Anton S. Petrova,1, Burak Gulena, Ashlyn M. Norrisa, Nicholas A. Kovacsa, Chad R. Berniera, Kathryn A. Laniera, George E. Foxb, Stephen C. Harveyc, Roger M. Wartellc, Nicholas V. Huda, and Loren Dean Williamsa,1
We present a molecular-level model for the origin and evolution of the translation system, using a 3D comparative method. In this model, the ribosome evolved by accretion, recursively adding expansion segments, iteratively growing, subsuming, and freezing the rRNA. Functions of expansion segments in the ancestral ribosome are assigned by correspondence with their functions in the extant ribosome. The model explains the evolution of the large ribosomal subunit, the small ribosomal subunit, tRNA, and mRNA. Prokaryotic ribosomes evolved in six phases, sequentially acquiring capabilities for RNA folding, catalysis, subunit association, correlated evolution, decoding, energy-driven translocation, and surface proteinization. Two additional phases exclusive to eukaryotes led to tentacle-like rRNA expansions. In this model, ribosomal proteinization was a driving force for the broad adoption of proteins in other biological processes. The exit tunnel was clearly a central theme of all phases of ribosomal evolution and was continuously extended and rigidified. In the primitive noncoding ribosome, proto-mRNA and the small ribosomal subunit acted as cofactors, positioning the activated ends of tRNAs within the peptidyl transferase center. This association linked the evolution of the large and small ribosomal subunits, proto-mRNA, and tRNA.

Image
The first six phases of the accretion model of ribosomal evolution. In Phase 1, ancestral RNAs form stem–loops and minihelices. In Phase 2, the LSU catalyzes the condensation of nonspecific oligomers. The SSU may have a single-stranded RNA-binding function. In Phase 3, the subunits associate, mediated by the expansion of tRNA from a minihelix to the modern L shape. LSU and SSU evolution is independent and uncorrelated during Phase 1–3. In Phase 4, evolution of the subunits is correlated. The ribosome is a noncoding diffusive ribozyme in which proto-mRNA and the SSU act as positioning cofactors. In Phase 5, the ribosome expands to an energy-driven, translocating, decoding machine. Phase 6 marks the completion of the common core with a proteinized surface (the proteins are omitted for clarity). The colors of the phases are the same as in Fig. 2. mRNA is shown in light green. The A-site tRNA is magenta, the P-site tRNA is cyan, and the E-site tRNA is dark green.


Other sources talking about the same article

Here is one written by the same authors:
Ribosome and the origin of life
Anton Petrov and Loren Williams
The ribosome in three-dimensions shows us that the exit tunnel was a central theme of all phases of its evolution. The tunnel was continuously extended and rigidified. The synthesis of non-coded peptides of increasing length conferred advantage as some reaction products bound to the ribosome. The ribosome sequentially gained capabilities for RNA folding, catalysis, subunit association, correlated subunit evolution, decoding and energy-driven translocation. Surface proteinization of the decoding ribosome was one driver of a more general proteinization of other biological processes, giving rise to modern biology. The ribosome spawned the existing symbiotic relationship of functional proteins and informational nucleic acids.


From a university (not written by the authors, but quotes both the authors and the paper)

Looking for the Origin of Life Inside a 4 Billion-Old Molecular Machine
Crystal structures of the ribosome suggest coevolution of RNA and proteins.
Sep 13, 2016 | Atlanta, GA

How did life on Earth originate from simple molecules? This question is one of the deepest, most fundamental questions of science, and it remains unanswered.

In Georgia Tech’s College of Sciences, scientists are trying to decipher the origin of life. Among them isLoren D. Williams, a professor in the School of Chemistry and Biochemistry and a member of the Parker H. Petit Institute of Bioengineering and Biosciences.

For Williams, part of the answer has to come from the ribosome. This gigantic molecular machine comprising ribonucleic acids (RNA) and proteins enables a key distinction of life: translation of genetic information to proteins.

How did translation begin? Work in Williams' lab suggests that translation is the product of molecular symbiosis, that ancestors of RNA and protein were molecular symbionts, and that life arose from the coevolution of proteins and RNA. That startling notion challenges the popular “RNA world” hypothesis of the origin of life. That world posits a time when life was based only on RNA, RNA-catalyzed transformations, and RNA-based genetic material; proteins, the ribosome, and translation appeared later.

At the meeting of the American Chemical Society in Philadelphia, Williams makes the case that the early history of the ribosome is also the history of the origin of life.

Williams and his coworkers base their conclusions on meticulous analysis of the “fossil record” in all ribosomes. As trees imprint events in their rings, or ice cores suspend time by preserving matter in frozen columns, ribosomes are time machines, Williams says, one “that allows us to look at the behaviors of ancient molecules 3.8 billion years ago.”

Crystal structures indicate that the modern ribosome grew by accretion, Williams says. By peeling away the layers deposited in the ribosome over almost 4 billion years, Williams and coworkers reached inside the so-called common core, which is the common denominator and oldest part of biology. Deep inside is the peptidyl transferase center, which links amino acids through peptide bonds “This part of the ribosome originates in chemistry,” Williams says. “It is pre-biology.”

If two amino acids are located within the peptidyl transferase center, they will easily form a peptide bond. “But as soon as you do that in the absence of the ribosome, the ends of the amino acids come together, forming a cyclic structure,” Williams says. Polymers cannot form. But if the ends are kept apart, by the primitive ribosome, a chain of peptide bonds could grow into a polymer.

As it happens, a feature of the ancient ribosome is a hole in the middle, foreshadowing the tunnel through which proteins leave modern ribosomes after they are made. “We think that an original function of the ribosome was not to catalyze peptide bond formation but to keep amino acids from forming cyclic structures and thereby form longer peptides,” Williams says.

The tunnel through which all proteins pass is a constant in the evolution of the ribosome. By examining crystal structures and mapping how modern ribosomes grew from the common core, Williams gleaned that ribosomes evolved to make this tunnel long and rigid.

Why? Williams suggests that without a long tunnel, a synthesized protein would fold at once, become active, and start eating the ribosome’s structure. “The tunnel is saying to the protein, no you cannot become functional yet.”

Ribosome crystal structures suggest something else: When early ribosomes made small peptides that were not capable of folding, some of these peptides stuck to and accreted on the ribosome. “We think the ribosome started making peptides in the first place to give itself greater stability,” Williams says. In making peptides that became bound to the ribosome like scaffolding, the ribosome became bigger and more stable.

As evidence, Williams presents the protein fossils in ribosomes. The oldest ones are frozen random coils “That’s the first thing we think the ribosome made. They got stuck, they didn’t fold. They don’t look like modern proteins.”

Next are isolated beta hairpins. “Nowhere else in biology will you see isolated beta hairpins without other protein around it,” Williams notes. “Only in the core of the ribosome do you see beta hairpins surrounded by RNA.” These isolated beta hairpins are the most ancient folded proteins in biology, he says.

Then come more modern proteins, made of beta sheets and alpha helices, with hydrophobic exteriors and hydrophilic interiors and the ability to fold to globular forms.

“Our results show that protein folding from random-coil peptides to functional polymeric domains was an emergent property of the interactions of ribosomal RNA and peptides,” Williams says. “The ribosome is the cradle of protein evolution.”

Along with Nicholas V. Hud, a professor at the School of Chemistry and Biochemistry and the director of the Center for Chemical Evolution, Williams and other origin-of-life researchers in Georgia Tech propose that chemical evolution—driven by assembly and other processes that increase stability—gradually converted to biological evolution, involving genes, enzymes, and ribosomes.

“We believe that chemical evolution was driven by assembly,” Williams says. “In biology, things that are assembled live longer chemically than those that are not. A folded protein is chemically stable. Unfold it, and it falls apart.” So it was in chemical evolution. Things that could assemble existed longer than those that couldn’t.

“If you had a molecule that could assemble and make peptides that bound to it, and they co-assemble, all of a sudden you have something better,” Williams says. “We think the reason proteins came into biology was that they stabilized the ribosome and protected it from degradation. The ribosome was looking out for itself. It was an evolutionary process by the ribosome, for the ribosome, and of the ribosome.

“We have the historical record or molecules. These things are preserved in the ribosome, we can see them. There is a molecular record of the origin of life.”


There is even an awesome animation about this!!


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"Ignorance more frequently begets confidence than does knowledge: it is those who know little, and not those who know much, who so positively assert that this or that problem will never be solved by science."
Charles Darwin
Sat Mar 11, 2017 7:15 pm
RumraketUser avatarPosts: 956Joined: Fri Jun 25, 2010 7:49 am Gender: Male

Post Re: Mindboggling result of Ribosomal RNA sequence analysis

Thank you for the references. I read the newest one recently, amazing stuff. One of the members of the team that did the analysis recently gave a NASA Astrobiology Symposium talk here:
"Nullius in verba" - Take nobody's word for it. https://en.wikipedia.org/wiki/Nullius_in_verba
Extraordinary claims require extraordinary evidence.
Sat Mar 11, 2017 9:36 pm
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