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kimera
2005-Oct-02, 09:21 PM
My question is about changes on base-pairs versus addition of new ones. I see how base pairs could change but not how new ones could be added because I would think that the addition of any new ones would throw off the entire codon sequence. I also don't understand how it could happen in the first place, with cellular defense mechanisms and the low probability that any resulting addition/change would actually be viable, and match up to a corresponding codon.

I looked on talkorigins but couldn't find anything.

Thanks.

TheBlackCat
2005-Oct-02, 10:04 PM
Well, there are a number of mechanisms. It is true that adding a base pair in a part of an unique gene that is coding for a protein will almost always render that protein inoperable. However, this is only a case if both those conditions are met. There are a number of situation in which that might not be the case.

First, the simplest is when there are multiple copies of the same gene. There are mechanisms which I am not very familiar with by which individual complete genes may be duplicated in a life-form's genome (I should be learning them soon). These include various proteins that duplicate segments as well as crossing over, a mechanism by which genes can shift from one chromosome to another. Obviously, once a gene has been duplicated one copy of the gene can mutate all it wants without affecting the cell's ability to make the protein, since the other copy of the gene can still produce sufficient amounts of the protein to supply the cell's need. This, as I understand it, is thought to be the mechanism by which the clotting cascade evolved. Parts duplicated, then mutated to catalyze the triggering of the original. Then these parts duplicates and mutated to catalyze the formation of the new molecule. Repeat several times and you have a cascade where each stage catalyzes the triggering of the next stage.

Another mechanism involves introns and exons. In eukaryote (i.e. not bacteria) DNA, the actual DNA code is usually not the final code that is read to make the protein. The DNA is converted into RNA, then parts of the RNA are removed and the remaining bits recombined to form a new RNA sequence. This shorter sequence is then read to make proteins. However, which sections of a given RNA are deleted and which are kept is not always the same. Sometime some sections of the RNA are kept, and other times other sections are kept. This way a single RNA, and thus a single gene, can code for a wide variety of proteins. Not all possible versions of the final RNA are useful, some have formed that do not code for anything and thus changes to those sections do not adversely affect the organism (unless they begin coding for something toxic) This means parts of a gene can grow, shrink, and change freely without altering the function of other sections. If these mutations suddenly make something useful, then the organism has a new, useful protein. I am not exactly clear on whether all combinations are synthesized or only specific one, or if it varies depending on the gene. Some sections may have to undergo some change to be recognized as useful sections.

Finally, for most eukaryotic organisms there are two copies of most genes. That means one gene can be mutated while still allowing the other to function normally. If this change on its own does not impede the function of the organism it can be what is called a "recessive" allele, an allele that only come into affect if two copies of the gene are present. This way you can get mutant genes without adversely affecting the organism, assuming the organism only has one copy of the gene. If the organism has two copies, they cannot produce the normal protein and can die as a result. Most human genetic disorders are of this sort. Because they only affect a small proportion of the creatures carrying them, they can persist in the population for long periods of time and can mutate freely during that time, possibly forming something useful. Some of these genes are lethal if an organism has two but can be helpful if an organism only has one. For instance, malaria cannot survive in people who have one sickle-cell anemia genes, but the people are not significantly affected by it. Likewise, people who have a single cystic fibrosis gene appear to be resistant to the bubonic plague and typhoid fever, even though they are not significantly harmed by the gene. However, these genes are lethal if someone has two copies.

I am not sure based on your post if you know this or not, but there is something to keep in mind with DNA. Every possible combination of 3 DNA bases has a corresponding codon that goes with it. The DNA is what is called "degenerate", there are usually several different DNA triplets that code for a certain amino acid. So no matter what triplet you put together, you will always find either an amino acid or stop codon that goes with it. The problem is that adding or deleting base pairs (called frame shift mutations) will alter every codon after them (assuming they are not done in a multiple of 3). This is because it the starting and stopping point of each codon changes.

Say you have a sequence like this:

AAGTACGTTAGTAAGCGCATGGCTAGC...

Starting from the first base, the triplets will be as follows

AAG|TAC|GTT|AGT|AAG|CGC|ATG|GCT|AGC...

Say, however, you add a new base after the 5th one:

AAGTAACGTTAGTAAGCGCATGGCTAGC...

The triplets will now be as follows:

AAG|TAA|CGT|TAG|TAA|GCG|CAT|GGC|TAG|C...

As you can see, every codon after the addition has been completely changed. This means it is most likely every amino acid has also been changed. Frame shift mutations are very serious, and it is unlikely they could be viable in a coding segment of DNA unless they occurred near the very end of the gene. This particular change actually causes the fourth codon to change from coding for a serine amino acid residue to coding for a "stop" codon, which would cause the ribosome to stop synthesizing the protein completely and thus terminate the protein after only 3 amino acids have been added instead of the dozens, hundreds, or even thousands normally found in proteins. This is a common problem with frame shift mutations. (that stop codon was not intential, BTW, I just types in a random series of bases and that is what happened)

kimera
2005-Oct-03, 10:27 PM
Thank you for your response. Would you happen to know any websites/books that go into more detail about this subject?

TheBlackCat
2005-Oct-03, 11:23 PM
I'm afraid not. I learned this in my Molecular Biology courses, I am not aware of any popular science books that cover this topic (although there probably are some).