# Which was the origin, DNA, RNA or Protein?

by Skwrl
Tags: origin, protein
 P: 6 Hello! I'm looking for information, articles and theories about which could have been the original molecule of life: DNA, RNA or protein. Most of what I've found is based on the RNA world theory (which I think is pretty well explained and sounds plausible), but I haven't found out any well-explained counter-theories for that. So now I'm wondering: are there any other plausible theories that that one? Is there any evidence, that proteins or DNA could have been the origin of life? Are there any scientific articles written about those? (Well, of course there must be, but I just haven't found them...) Any help would be really welcome and thank you already in advance! :) I'm a Finnish biology student, so pardon if there are any grammatical errors or stupid word choices :P
 P: 605 For an overall view, wikipedia would be a good place to start. http://en.wikipedia.org/wiki/Abiogenesis It tells about many other models besides the RNA World Hypothesis and there are plenty of resources at the bottom of the page. Note however that there is no universally accepted theory on abiogenesis.
 P: 530 RNA world hypothesis - Wikipedia, the free encyclopedia Modern metabolism as a palimpsest of the RNA world Though DNA is more chemically stable than RNA, it is nevertheless secondary. DNA nucleotides are made from RNA ones. First, some hydrogen is added to the ribose, chemically reducing its 2' -OH group to -H, making deoxyribose. Then, a methyl group is added to the uracil groups, making thymine groups. Biochemistry II: Deoxynucleotide Synthesis DNA also has only one function: containing master copies of genetic information. RNA has several functions, and because of its chemical similarity, DNA could easily fill in for RNA there. RNA has several functions: List of RNAsMessenger RNA: carries genetic information from DNA master copies Self-splicing: some messenger-RNA molecules can do that Transfer RNA: for translating nucleotide triplets into amino acids for proteins Ribosomal RNA: the most essential parts of ribosomes, protein-assembly complexes Ribozymes: RNA can act as an enzyme. Ribosomal RNA can be interpreted as a ribozyme, and self-splicing is a ribozyme sort of activity Gene-regulation RNA's RNA primers in DNA replicases, enzymes for copying DNA RNA also appears in some enzyme cofactors: ATP, cyclic AMP, NAD, FAD, Coenzyme A, Vitamin B12 The presence of RNA in several of these functions is rather odd when one considers the widespread use and versatility of protein enzymes and the chemical similarity of DNA. This suggests that their presence of RNA is a vestigial feature. Since the most important parts of the protein-synthesis mechanism are RNA, this means that proteins are also secondary. So we end up at the RNA world, one where RNA acted as both information storage and enzymes. Some enzymes had post-transcriptional modification of RNA bases, like in transfer RNA and some ribozymes, and some used add-on cofactors, like amino acids and porphyrins. While the RNA world has become widely accepted, it faces the problem of the origin of the RNA. It's difficult to make it using prebiotic-synthesis techniques. I've seen some speculation that ribose was not the first backbone molecule of informational molecules, that there was originally something other than the R in RNA. But beyond that it's hard to say. So we have a sequence: Prebiotic world ??? RNA world Proteins added DNA added
 Sci Advisor P: 5,517 Which was the origin, DNA, RNA or Protein? Stuart Kauffman, in "The Origins of Order", has a very good discussion regarding DNA/RNA-first and protein-first theories. There is evidence supporting RNA-first (all life is based on DNA or RNA as a stable data storage form, RNA can autocatalyze) and evidence opposing RNA-first (so-called 'nude genes' do not appear to *both* replicate and synthesize proteins). Similarly, there is evidence supporting protein-first (peptides can be easily created in the absence of RNA) and evidence opposing (proteins cannot replicate). What Kaufmann shows is that if *both* short peptide sequences and RNA sequences are present, the combinatorics of their reactions leads to an autocatalytic set of reactions when the length of peptide sequence or RNA sequence is still very short- 7 or so monomers. In this model, self-reproducing autocatalytic polymer systems emerge fairly easily, and small additions to the polymer length allow exponentially more complexity to be encoded, which is a model for evolution.
 P: 530 Yes, it's possible to make "thermal proteins" or "proteinoids", but they don't help make other thermal proteins, and they don't transmit information about themselves to other thermal proteins. It's something like fire, which can reproduce itself, but which does not transmit information about itself in the process. Nucleic acids, however, can transmit information about themselves; each strand can serve as a template for another strand. When James Watson and Francis Crick discovered the double-helix structure of DNA, they noted that "It has not escaped our attention that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." That was the template mechanism, which was later abundantly confirmed. The template mechanism for transmitting information is a very simple one, but has anyone ever succeeded in constructing a protein system that can do that? I don't know of anyone who has done so. An RNA world does not rule out thermal proteins or randomly-assembled ones. In fact, transfer and ribosomal RNA would be a RNA-world invention for making nonrandom proteins.
 Sci Advisor P: 8,555 Woese makes the same point as Ipetrich does in post #5 that the RNA world does not mean that proteins did not exist at the same time. http://www.ncbi.nlm.nih.gov/pubmed/12077305
 P: 530 There is an additional conundrum with RNA and proteins. Asymmetry. It's a conundrum because the wrong asymmetry can cause compatibility problems. With the exception of glycine, the "backbone" part of protein-forming atoms has an asymmetric carbon atom, one where all four molecular groups attached are in an antisymmetric configuration. There are two possible ones, which are mirror images.  side chain | H2N - C - COOH | H H | H2N - C - COOH | side chain In glycine, the side chain is hydrogen, which is why it does not have that asymmetry. The origin of the asymmetry of protein-forming amino acids has been much argued over, and I wish to avoid that subject for now. Ribose is much worse. It has 4 asymmetric carbon atoms. Deoxyribose cuts that down to 3, but it's made from ribose, and it emerged after ribose did. If ribose did not emerge directly from prebiotic, but instead took over from some other backbone molecule, that would resolve this conundrum.
 Mentor P: 5,463 Newscientist just published an article regarding the possibility of TNA along with RNA and DNA in the early world http://www.newscientist.com/article/...dge-world.html
P: 33
 Quote by mishrashubham For an overall view, wikipedia would be a good place to start. http://en.wikipedia.org/wiki/Abiogenesis It tells about many other models besides the RNA World Hypothesis and there are plenty of resources at the bottom of the page. Note however that there is no universally accepted theory on abiogenesis.

I went to this article and found this - 2nd paragraph -

"Most amino acids, often called "the building blocks of life", can form via natural chemical reactions unrelated to life, as demonstrated in the Miller–Urey experiment and similar experiments that involved simulating some of the hypothetical conditions of the early Earth in a laboratory.[1] Other equally fundamental biochemicals, such as nucleotides and saccharides can arise in similar ways."

Does anyone object to the use of "most"?

I actually conducted a reduced form Miller - Urey in 1969 and find the use of "most" to be excessive.
PF Gold
P: 645
 Quote by Murdstone I went to this article and found this - 2nd paragraph - "Most amino acids, often called "the building blocks of life", can form via natural chemical reactions unrelated to life, as demonstrated in the Miller–Urey experiment and similar experiments that involved simulating some of the hypothetical conditions of the early Earth in a laboratory.[1] Other equally fundamental biochemicals, such as nucleotides and saccharides can arise in similar ways." Does anyone object to the use of "most"? I actually conducted a reduced form Miller - Urey in 1969 and find the use of "most" to be excessive.
The "key" thing to note is the "and similar experiments". Most of life's amino acids do have a "natural synthesis" (or rather a effective way they could be synthesized naturally) worked out. PubMed is your friend
P: 530
Only some of the protein-forming amino acids are reasonably likely to be prebiotic. The rest may have been result of metabolic leakage. Furthermore, the prebiotic ones are more common in the last universal common ancestor (LUCA) of all present-day organisms. These ones are alanine, aspartate, glutamate, glycine, isoleucine, leucine, proline, serine, threonine, valine.

Evolution of Amino Acid Frequencies in Proteins Over Deep Time: Inferred Order of Introduction of Amino Acids into the Genetic Code
 To understand more fully how amino acid composition of proteins has changed over the course of evolution, a method has been developed for estimating the composition of proteins in an ancestral genome. Estimates are based upon the composition of conserved residues in descendant sequences and empirical knowledge of the relative probability of conservation of various amino acids. Simulations are used to model and correct for errors in the estimates. The method was used to infer the amino acid composition of a large protein set in the Last Universal Ancestor (LUA) of all extant species. Relative to the modern protein set, LUA proteins were found to be generally richer in those amino acids that are believed to have been most abundant in the prebiotic environment and poorer in those amino acids that are believed to have been unavailable or scarce. It is proposed that the inferred amino acid composition of proteins in the LUA probably reflects historical events in the establishment of the genetic code.
Results:
 Using our approach, we have estimated the amino acid composition of a set of 65 proteins within the LUA. We infer that within this set of proteins many of the amino acids believed to have been most abundant in the prebiotic environment (Miller 1953<$REFLINK> , 1987<$REFLINK> ; Kvenvolden et al. 1970<\$REFLINK> ), including glycine, alanine, aspartic acid, and valine, were used more frequently within proteins of the LUA than within those of modern species. On the other hand, amino acids believed to have been rare or unavailable prebiotically, including cysteine, tryptophan, tyrosine, and phenylalanine, were generally used much less frequently within proteins of the LUA. This may reflect the order of addition of these two groups of amino acids to the genetic code.
P: 530
The origin of RNA-to-protein translation involves the origin of the ribosome, a structure composed of RNA and protein that acts as a workbench for this process.

The information source is strands of messenger RNA (mRNA), and the protein's future amino acids are attached to small snippets of RNA called transfer RNA (tRNA). The AA's are added by aminoacyl tRNA synthetase (aaRS) enzymes.

At the ribosome, a tRNA with an AA gets selected whose "anticodon" region fits against a triplet of nucleotides (the "codon") in the mRNA at a certain spot. The AA gets attached to the growing protein chain, the AA-less tRNA gets ejected, and the mRNA gets advanced so its next triplet gets used for translation.

In this complicated molecular machine, the RNA's are the central parts, and the proteins are assistants. So the ribosome likely started off as the RNA parts only and gradually acquired proteins.

Origin and Evolution of the Ribosome
George E. Fox
 The modern ribosome was largely formed at the time of the last common ancestor, LUCA. Hence its earliest origins likely lie in the RNA world. Central to its development were RNAs that spawned the modern tRNAs and a symmetrical region deep within the large ribosomal RNA, (rRNA), where the peptidyl transferase reaction occurs. To understand pre-LUCA developments, it is argued that events that are coupled in time are especially useful if one can infer a likely order in which they occurred. Using such timing events, the relative age of various proteins and individual regions within the large rRNA are inferred. An examination of the properties of modern ribosomes strongly suggests that the initial peptides made by the primitive ribosomes were likely enriched for l-amino acids, but did not completely exclude d-amino acids. This has implications for the nature of peptides made by the first ribosomes. From the perspective of ribosome origins, the immediate question regarding coding is when did it arise rather than how did the assignments evolve. The modern ribosome is very dynamic with tRNAs moving in and out and the mRNA moving relative to the ribosome. These movements may have become possible as a result of the addition of a template to hold the tRNAs. That template would subsequently become the mRNA, thereby allowing the evolution of the code and making an RNA genome useful. Finally, a highly speculative timeline of major events in ribosome history is presented and possible future directions discussed.
P: 530
I've found RNA Second Messengers and Riboswitches: Relics from the RNA World? by Ronald R. Breaker
 Some riboswitches and their ligands may be relics of signaling networks used when organisms relied on RNA instead of DNA and proteins. ompelling evidence supports the hypothesis that modern cells descended from organisms whose components were made entirely of RNA. Scientists who helped formulate this “RNA World” hypothesis for the evolution of life have identified many characteristics of modern cells that strongly suggest RNA once ruled the planet. For example, the existence of self-cleaving and self-splicing ribozymes that cut and ligate RNAs demonstrates that at least some RNA-processing reactions can be catalyzed without the need for proteins. Also, the existence of ribosomal RNAs that build all genetically encoded proteins emphasizes the fact that today’s organisms depend on RNA to carry out fundamental biochemical processes. Even many nucleotide-like coenzymes that are near universal in all life forms likely first appeared in RNA World organisms. The RNA World hypothesis is appealing because it helps explain the arcane characteristics of genetic and biochemical processes in modern cells. Why do all cells use ribosomal RNAs, and not protein enzymes, to stitch together amino acids to make polypeptides? Most likely, the ribosome’s peptidyl transferase center is an evolutionary descendent of an ancient ribozyme that first catalyzed this reaction before protein enzymes evolved. Why do so many coenzymes, such as adenosylcobalamin (AdoCbl), thiamin pyrophosphate (TPP), flavin mononucleotide (FMN), S-adenosylmethionine (SAM), molybdenum cofactor (Moco), and tetrahydrofolate (THF), all carry recognizable fragments of RNA nucleotides or derive from nucleotide precursors? Perhaps these compounds served as coenzymes for metabolic ribozymes of the RNA World, and they have been preserved as legacies from a time before protein enzymes existed.
Seems like the RNA-world hypothesis is getting more and more into the mainstream of origin-of-life research.

The universal ancestor was a thermophile or a hyperthermophile.[Gene. 2001] - PubMed - NCBI
The universal ancestor and the ancestor of bacteria were hyperthermophiles. [J Mol Evol. 2003] - PubMed - NCBI
The universal ancestor was a thermophile or a hyperthermophile: tests and further evidence. [J Theor Biol. 2003] - PubMed - NCBI
Di Giulio M

The Last Universal Common Ancestor (LUCA) and the ancestors for domains Bacteria and Archaea (LBCA and LACA) are all (hyper)thermophiles. However, the Last Eukaryotic Common Ancestor (LECA) was a mesophile, preferring temperatures that we'd consider "normal".

The universal ancestor and the ancestors of Archaea and Bacteria were anaerobes whereas the ancestor of the Eukarya domain was an aerobe. [J Evol Biol. 2007] - PubMed - NCBI
Di Giulio M

His (her?) method was to correlate proteins' amino-acid content with their organisms' temperature and oxygen tolerances. He then estimated the temperature and oxygen tolerances of reconstructed ancestral proteins.

These results are consistent with speculations about origin in hydrothermal vents and the like. The LUCA, LBCA, and LACA would thus not be very distant from the original organism. These results are also consistent with atmosphere oxygenation being the result of O2-releasing photosynthesis. Organisms that lived before that photosynthesis had evolved would have to have been anaerobes. That necessarily includes the ancestors of cyanobacteria or blue-green algae, the first O2-releasers. Those ancestors include the LBCA and the LUCA but not the LACA, so it's interesting that the LACA was also anaerobic.
 P: 530 The LECA, however, is a latecomer, originating after the atmosphere got oxygenated. That was about 2.5 billion years ago, the Great Oxygenation Event. It was a hybrid organism, containing a mishmash of genes from several organisms. The informational systems are largely from Archaea, and the metabolic ones largely from Bacteria. The LECA had mitochondria, which are descended from some alpha-proteobacterium that an ancestor of the LECA had "eaten". Mitochondria use O2, consistent with the LECA being O2-tolerant. Mitochondrion-less present-day protists have lots of evidence of former mitochondria: Genetic evidence for a mitochondriate ancestry in the 'amitochondriate' flagellate Trimastix pyriformis. [PLoS One. 2008] - PubMed - NCBI Mitochondrion-related organelles in eukaryotic protists. [Annu Rev Microbiol. 2010] - PubMed - NCBI Chloroplasts are descended from some cyanobacterium that some early protist had "eaten", but that protist was not the LECA, but some descendant. Some protists later "ate" other photosynthetic protists, producing an endosymbiosis Russian-doll effect. The LECA also had a well-defined cell nucleus, complete with Nuclear Pore Complexes, as can be determined by comparing NPC proteins. Evolution: functional evolution of nuclear structure. [J Cell Biol. 2011] - PubMed - NCBI Evolution of the karyopherin-β family of nucleocytoplasmic transport factors; ancient origins and continued specialization. [PLoS One. 2011] - PubMed - NCBI Evidence for a shared nuclear pore complex architecture that is conserved from the last common eukaryotic ancestor. [Mol Cell Proteomics. 2009] - PubMed - NCBI Comparative genomic evidence for a complete nuclear pore complex in the last eukaryotic common ancestor. [PLoS One. 2010] - PubMed - NCBI
 Other Sci Sci Advisor P: 1,385 It's worth noting that the ancestral sequence reconstruction methods used by Di Giulio to infer the thermostability of ancient proteins are far from perfect, rely on many untested (an in some cases incorrect) assumptions, and suffer from many biases. For example, some have suggested that these methods tend to overestimate the thermostability of ancient proteins, putting into question the main conclusions of the studies you cite above. You can read one such study below: Williams PD, Pollock DD, Blackburne BP, Goldstein RA (2006) Assessing the Accuracy of Ancestral Protein Reconstruction Methods. PLoS Comput Biol 2(6): e69. doi:10.1371/journal.pcbi.0020069
 P: 6 Wow, thanks a lot for all your replies! It's been interesting to read (or at least skim) the articles you have linked and see all the different aspects and results :) Thank you once more!

 Related Discussions Biology, Chemistry & Other Homework 13 Biology 2 Computing & Technology 0 Biology 3