RNA's evolutionary history and the RNA world
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1) RNA likely served as the first genetic material of life and still performs many critical functions in cells today, providing evidence that early life was based on RNA. 2) RNA can act as messenger RNA to carry genetic information, spliceosomal RNA to cut and join mRNA, self-splicing RNA, transfer RNA to recognize mRNA codons during translation, and ribosomal RNA that links amino acids during protein synthesis. 3) RNA's ability to fold into complex structures, catalyze chemical reactions, specifically bind other molecules, and self-replicate allowed it to carry genetic information and catalyze reactions independently before DNA and proteins evolved.
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RNA's evolutionary history and the RNA world
- 1. Evolution connection: Transcription and translationEvolution connection: Transcription and translation Learning goals: Students will understand that 1) RNA was likely the first genetic material of life, and 2) the many different functions that RNA is capable of performing in the cell today constitute evidence that life was once based on RNA. For the instructor: This short slide set relates the role of RNA in the processes of transcription and translation to RNA’s evolutionary history and the remnants of the RNA world. To integrate it best, use these slides immediately after you’ve discussed transcription and translation. This slide set could be shortened, if you wish, by cutting slides 3, 4, 7 and 8. Each of the following slides comes with a sample script for the instructor. To review this script, download the PowerPoint file and view the Notes associated with each slide.
- 2. Evolution connection: Transcription and translationEvolution connection: Transcription and translation Complementary DNA strands RNA strand Flu virus anatomy RNA RNA: Jack-of-all-trades 1) mRNA - carries genetic information
- 3. Evolution connection: Transcription and translationEvolution connection: Transcription and translation RNA: Jack-of-all-trades 2) Spliceosome – RNA cuts and rejoins a mRNA molecule
- 4. Tetrahymena image from Robinson R (2006) Ciliate Genome Sequence Reveals Unique Features of a Model Eukaryote. PLoS Biol 4(9): e304. doi:10.1371/journal.pbio.0040304 Evolution connection: Transcription and translationEvolution connection: Transcription and translation RNA: Jack-of-all-trades 3) Self-splicing – some RNA can splice itself
- 5. Evolution connection: Transcription and translationEvolution connection: Transcription and translation RNA: Jack-of-all-trades 4) tRNA – recognizes mRNA codons during the process of translation
- 6. Ribosome image from the Center for Molecular Biology of RNA at the University of California, Santa Cruz. Evolution connection: Transcription and translationEvolution connection: Transcription and translation RNA: Jack-of-all-trades 5) rRNA – links amino acids together into a protein ribosome (made of rRNA) chain of amino acids peptide bond forming
- 7. Evolution connection: Transcription and translationEvolution connection: Transcription and translation RNA: Jack-of-all-trades 6) Self-replicating – some RNA can copy itself.
- 8. Evolution connection: Transcription and translationEvolution connection: Transcription and translation What makes RNA so powerful? Ribozyme structure comes from Scott, W.G., Finch, J.T., Klug, A. (1995) The crystal structure of an all-RNA hammerhead ribozyme: a proposed mechanism for RNA catalytic cleavage. Cell 81: 991-1002 • It can fold up • Some of its bases can catalyze chemical reactions • It is highly specific (i.e., complementary) tRNA hammerhead ribozyme RNA base pairing
- 9. Evolution connection: Transcription and translationEvolution connection: Transcription and translation RNA • Carries genetic information • Catalyzes chemical reactions • Binds to other molecules • Self-replicates Can go it alone! DNA • Carries genetic information Needs help!
- 10. Evolution connection: Transcription and translationEvolution connection: Transcription and translation So which came first? Which came first, DNA or proteins?
- 11. Evolution connection: Transcription and translationEvolution connection: Transcription and translation Which came first, DNA or proteins? Neither. Because it was all RNA ... The RNA world!
- 12. Evolution connection: Transcription and translationEvolution connection: Transcription and translation Selection for efficient self-replication:
- 13. Evolution connection: Transcription and translationEvolution connection: Transcription and translation Chi, Y., Martick, M., Lares, M., Kim, R., Scott, W. G., and Kim, S. (2008). Capturing hammerhead ribozyme structures in action by modulating general base catalysis. PLoS biology. 6: e234. Lincoln, T. A., and Joyce, G. F. (2009). Self-sustained replication of an RNA enzyme. Science. 323: 1229-1232.
Editor's Notes
- We’ve just learned about some of the many jobs in the cells that RNA performs—especially when it comes to protein synthesis. What are some of those jobs? (CLICK) mRNA carries genetic information. In humans, mRNA carries information originally encoded in the DNA. (CLICK) But for many viruses (like the flu virus), RNA is the only genetic material. (HIV has RNA as its genetic material as well, but this is reverse-transcribed into DNA inside the host.)
- Before mRNA is translated into protein, certain regions of the mRNA called introns must be cut out. This is done by the spliceosome, which is made of proteins and RNA. However, within the spliceosome, it is RNA that actually does the job of clipping and rejoining the mRNA molecule. Clipping and rejoining the mRNA requires RNA to act like an enzyme and catalyze chemical reactions.
- Some RNA can splice itself. It doesn’t need a spliceosome (a separate strand of RNA) or any help from a protein. It just folds up and clips out its own introns. This happens in certain protists (e.g., Tetrahymena, shown here).
- Parts of tRNA molecules called anti-codons recognize codons in mRNA during the process of translation.
- Ribosomes are made up of RNA and proteins, but it is the RNA components of the ribosome that have the catalytic job of linking amino acids together to form a protein.
- In 2009, biologists discovered that some RNA enzymes, or ribozymes, can propagate themselves without outside help from proteins or other molecules. The RNA enzymes catalyzed reactions that produced even more copies of the original enzymes. Note to the instructor: This diagram of RNA self replication shows an RNA enzyme catalyzing the joining of oligonucleotides into a replicate of the original RNA. For clarity, this depiction is somewhat simplified from the system that was described in the original research on this topic. In the original research, there were two distinct RNA enzymes that mutually catalyzed each others’ synthesis from two oligonucleotides, forming a self-replicating system.
- RNA can do a ton of different jobs. DNA on the other hand, can only carry genetic information. What makes RNA so powerful? Why can it do so much? Any ideas? (CLICK) First, it can fold up. Because it is usually single stranded, RNA’s bases can pair with one another and form 3-D structures that vary depending on the sequence of its bases. Differently shaped molecules can do different jobs. (CLICK) Second, some of its bases can catalyze chemical reactions. For example, guanine (a nucleotide) can act as a base and help catalyze chemical reactions by temporarily accepting a proton. This sort of catalysis seems to be what the hammerhead ribozyme (shown here) uses to cleave itself. (CLICK) Third, the order of bases in the RNA molecule allow it to recognize other specific sequences. This means that it doesn’t go around splicing molecules randomly or catalyzing random chemical reactions but can recognize specific sequences and do its job in the right place.
- DNA is great for carrying genetic information. It’s stable, and its structure means that it always has a back up if there’s a problem with one strand. (CLICK) But DNA needs help to get anything done. (CLICK) RNA, on the other hand, can go it alone.
- All of this may help answer a long-standing question in evolutionary biology about how life first arose: Which came first, DNA or proteins? This is an important question about the origin of life. (CLICK) After all, in today’s world, DNA codes for enzymes (like DNA polymerase), and enzymes like DNA polymerase are necessary to make more DNA—(CLICK) so which came first?
- Scientists currently think that the answer is neither, because RNA came first and it did it all—stored genetic information, copied itself, and catalyzed all the necessary chemical reactions. The RNA world hypothesis suggests that in the earliest stages of life’s evolution, DNA and proteins weren’t around. Instead, everything was done by RNA.
- In the RNA world, perhaps an RNA molecule arose that could copy itself. Once this happened, natural selection began. The copying would not have been perfect, and any copying errors that happened to cause the RNA to copy more efficiently would be favored. And if an RNA happened to be able to build a polypeptide that helped it replicate even faster, that RNA sequence would be favored. Ultimately, of course, an evolutionary transition was made from using RNA as the basic molecule of heredity to using DNA—but we still see vestiges of the RNA world in all the different jobs RNA performs in the cell.