Digital Biology Friday: Free to evolve? - the answer

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Sandra Porter
Last week I posted an image with two molecules (below the fold), one protein and one nucleic acid, and asked you about the probability of finding similar molecules in different species. You gave me some interesting answers. DAG made me clarify my question by asking what I meant by "similarity." I was wondering whether I would be likely to find a statistically relevant match by doing a BLAST search and I hadn't really thought about the cutoff values. I decided to guess and say that that the protein would be about 30% similar and the nucleic acid about 60%. Paul gave me some answers based on probability and math. He also made me give him a hint - both of the molecules are essential for life. At least one of them, though, belongs to a multigene family and it may be possible to delete one or more copies of it. I don't know. Luna_the_cat gave one of the best answers, at least for the protein part. Yes! the shapes of the molecules are important. skerr is right about the protein interacting with the nucleic acid but the suggestion that the exact nucleic acid sequence is unimportant is wrong. What is right? First the answer: For both molecules, the answer is A. There is a high probability of finding a similar sequence in other organisms, all three kingdoms of life have similar sequences. Why? and how could know that from looking at the picture? I added some labels to the picture to help me discuss it. i-40b6bc9ca408c15547aa7375dd7d9a95-interaction_labels.gif The most important characteristic in this picture, as Luna pointed out, is that there are a lot of interactions between different parts of the molecules. This isn't a coincidence. Molecules don't get to touch each this closely unless both molecules have residues with the correct shape and the correct charge. Let's look at the protein If we look at part A, we see that the protein is in very close contact with the backbone of the nucleic acid (it's RNA by the way). If you above and below the strange shape that I drew, we also see that certain residues in the protein touch certain bases in the RNA. I know all the residues in this image look alike, but they're not. For these molecules to come into contact and bind this tightly, they must have: 1. The correct shape. 2. The correct charge. In the case of the protein, if a mutation occurs that replaces one amino acid one with another that has different physical properties, that mutation could very well change the shape of the protein and mess up the ability of these two molecules to get so close and cozy. If these two molecules can't close to each other, there might be more serious, life and death kinds of consequences. So, I say that this protein sequence is likely to be conserved and similar in different organisms. Changing this protein's sequence would most likely result in bad things and organisms with those sorts of mutations would not be likely to reproduce. Consequently, I think I should be able to find this protein sequence by doing a BLAST search. What about the nucleic acid? Why do I say that the structure of the nucleic acid is important too? Take a look at the part labeled B. This bit of nucleic acid is folded in a very interesting way. This is not a double-helix. This molecule has a secondary structure and is able to form this interesting shape because some bases pair with each other and some do not. In order for specific bases to pair with each other and form this secondary structure, they must be complementary. This means that these bases are constrained as far as their ability to change. Changing one base in pair could be a problem because it could disrupt the structure and mess with the shape. Altering the shape of the RNA could make it harder for the protein to bind, and you'd be left with a mess. So, I say that this RNA sequence is likely to be conserved as well. Many RNA molecules have enzymatic activity, too, that's related to their ablity to form cool shapes. Never underestimate RNA. Are there parts of these molecules that might be more free to evolve? Yes, I think so. Look at part C. Here is a base that's not paired with anyone and it's facing away from the rest of the structure. This base has more freedom than the other bases in this RNA or amino acids in the protein. At least, it looks that way in this structure. One last puzzle: I said that this pair of molecules is:
a. found in all three kingdoms of life b. at least one member of the pair belongs to a multi-gene family c. the nucleic acid is RNA.
Can you guess which type of RNA it might be?

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