Rumraket said:
Okay, here:abelcainsbrother said:
Origin of DNA
DNA can be considered as a modified form of RNA, since the “normal” ribose sugar in RNA is reduced into deoxyribose in DNA, whereas the “simple” base uracil is methylated into thymidine. In modern cells, the DNA precursors (the four deoxyribonucleoties, dNTPs) are produced by reduction of ribonucleotides di- or triphosphate by ribonucleotide reductases (fig. 1). The synthesis of DNA building blocks from RNA precursors is a major argument in favor of RNA preceding DNA in evolution. The direct prebiotic origin of is theoretically plausible (from acetaldehyde and glyceraldehyde-5-phosphate) but highly unlikely, considering that evolution, as stated by F. Jacob, works like a tinkerer, not an engineer.8,9
Figure 1. Metabolic pathways for RNA and DNA precursors biosynthesis: a palimpsest from the RNA to DNA world transition? The biosynthetic pathways for purine and pyrimidine nucleotides both start with ribose 5-monophosphate.
Figure 1
Metabolic pathways for RNA and DNA precursors biosynthesis: a palimpsest from the RNA to DNA world transition? The biosynthetic pathways for purine and pyrimidine nucleotides both start with ribose 5-monophosphate. The formation of the four bases requires several amino-acids, formate and carbamyl-phosphate. Nucleotide monophosphates (NMP) are converted into RNA precursors (NTP) by NMP kinases (k) and NDP kinases (K). These reactions probably are relics of the RNA-protein world. DNA precursors are produced from NDP and/or NTP by ribonucleotide reductases (RNR), except for dTTP, which results from methylation of dUMP. dTMP is produced from dUMP by Thymidylate synthases (ThyA or ThyX) and converted into dTTP by the same kinases that convert NMP into NTP. dUMP can be produced either by dUTPAse or by dCTP deaminase. In the U-DNA world, it could have been also produced by degradation of U-DNA. The mode of dTMP production clearly suggests that U-DNA was an evolutionary intermediate between RNA and T-DNA. Some viruses contain U-DNA, whereas others contain HMC-DNA (HMC= hydroxymethyl-cytosine). Transformation of C into HMC occurs at the level of dCMP, and conversion of dCMP into dHMCMP is catalyzed by a dCMP hydroxy-methyl transferase (dCMP HM transferase), which is homologue to ThyA (See refs. 11, 14, and 19 for more details).
Metabolic pathways for RNA and DNA precursors biosynthesis: a palimpsest from the RNA to DNA world transition? The biosynthetic pathways for purine and pyrimidine nucleotides both start with ribose 5-monophosphate. The formation of the four bases requires (more...)
The first step in the emergence of DNA has been most likely the formation of U-DNA (DNA containing uracil), since ribonucleotide reductases produce dUTP (or dUDP) from UTP (or UDP) and not dTTP from TTP (the latter does not exist in the cell) (fig. 1). Some modern viruses indeed have a U-DNA genome,10 possibly reflecting this first transition step between the RNA and DNA worlds. The selection of the letter T occurred probably in a second step, dTTP being produced in modern cells by the modification of dUMP into dTMP by thymidylate synthases (followed by phosphorylation).11 Interestingly, the same kinase can phosphorylate both dUMP and dTMP.11 In modern cells, dUMP is produced from dUTP by dUTPases, or from dCMP by dCMP deaminases (fig. 1).11 This is another indication that T-DNA originated after U-DNA. In ancient U-DNA cells, dUMP might have been also produced by degradation of U-DNA (fig. 1).
The origin of DNA also required the appearance of enzymes able to incorporate dNTPs using first RNA templates (reverse transcriptases) and later on DNA templates (DNA polymerases). In all living organisms (cells and viruses), all these enzymes work in the 5' to 3' direction. This directionality is dictated by the cellular metabolism that produces only dNTP 5' triphosphates and no 3' triphosphates. Indeed, both purine and pyrimidine biosyntheses are built up on ribose 5 monophosphate as a common precursor. The sense of DNA synthesis itself is therefore a relic of the RNA world metabolism. Modern DNA polymerases of the A and B families, reverse transcriptases, cellular RNA polymerases and viral replicative RNA polymerases are structurally related and thus probably homologous (for references, see a recent review on viral RNA-dependent RNA polymerases.)12 This suggests that reverse transcriptase and DNA polymerases of the A and B families originated from an ancestral RNA polymerase that has also descendants among viral-like RNA replicases. However, there are several other DNA polymerase families (C, D, X, Y) whose origin is obscure (we will go back to this point below).
If DNA actually appeared in the RNA world, it was a priori possible to imagine that formation of the four dNTPs from the four rNTPs was initially performed by ribozymes. Most scientists, who consider that the reduction of ribose cannot be accomplished by an RNA enzyme, now reject this hypothesis.9,13-19 The removal of the 2' oxygen in the ribose involves indeed a complex chemistry for reduction that requires the formation of stable radicals in ribonucleotide reductases. Such radicals would have destroyed the RNA backbone of a ribozyme by attacking the labile phosphodiester bond of RNA. Accordingly, DNA could have only originated after the invention of modern complex proteins, in an already elaborated protein/DNA world. This suggests that RNA polymerases were indeed available at that time to evolve into DNA polymerases (as well as kinases to phosphorylate dUMP).
Three classes of ribonucleotide reductases (I, II and III) have been discovered so far (for a review, see refs. 9, 16-19) (fig. 1). Although they correspond to three distinct protein families, with different cofactors and mechanisms of action, these mechanisms are articulated around a common theme (radical based chemistry). In all cases, the critical step is the conversion of a cysteine residue into a catalytically essential thiol radical in the active center.18 Recent structural and mechanistic analyses of several RNR at atomic resolution have suggested that all ribonucleotide reductases originated from a common ancestral enzyme, favoring the idea that U-DNA was invented only once.17,18 It has been suggested that either class III (strictly anaerobic) or class II (anaerobic but oxygen tolerant) represent the ancestral form, and that new versions appeared in relation to different lifestyles by recruiting new mechanisms for radical activation (class III in strict anaerobes and class I in aerobes).9,18
The origin of U-DNA in a protein/RNA world logically implies that the second step in the synthesis of DNA precursors, the formation of the letter T, was catalyzed by ancestral thymidylate synthase. For a long time, it was believed that modern thymidylate synthases were all homologues of E. coli ThyA protein, indicating that the letter T was invented only once. However, comparative genomics has revealed recently that ThyA is absent in many archaeal and bacterial genomes, leading to the discovery of a new thymidylate synthase family (ThyX).19 ThyX and ThyA share neither sequence nor structural similarity between each other and have different mechanisms of action,19,20 indicating that thymidylate synthase activity was invented twice independently (fig. 1). T-DNA might have appeared either in two different U-DNA cells, or the invention of a second thymidylate synthase might have occurred in a cell already containing a T-DNA genome. The first possibility would indicate that T-DNA itself has been invented twice, thus suggesting a strong selection pressure to select for uracil modification. In the second case, one should imagine that the new enzyme (either ThyA or ThyX) brought a selective advantage over the previous one in the organism where it appeared first.
Turns yout you were wrong.abelcainsbrother said:
I don't.abelcainsbrother said:
That statement is false. We can know that things have happened without having directly witnessed them, because the process leaves evidence behind. When we have evidence we don't need faith, that's the whole point of evidence.abelcainsbrother said:
That evidence has been provided.abelcainsbrother said:
Visaki said:
Darkprophet232 said:
Collecemall said:
abelcainsbrother said:
