Tuesday, December 15, 2009

Does Excess Genomic DNA Protect Against Mutation?

Many eukaryotic genomes have a large amount of "excess" DNA that doesn't have any of the functions we normally assign to DNA (protein-coding, regulatory, origins of replication, centromeres, RNA genes etc.). Many of us think this is junk DNA. It has no function and could easily be dispensed with.

One of the adaptive explanations for this excess DNA is that it protects the functional DNA from mutations. Ryan Gregory thinks this is a serious scientific hypothesis even though he's skeptical. He has a wonderful post that reviews the history of the idea and how the hypothesis should be tested [Does junk DNA protect against mutation?].

The bottom line is that this hypothesis is not taken very seriously by the scientific community for some very good reasons.

First, most spontaneous mutations in the germ line seem to be due to errors in DNA replication. The overall rate of evolutionary change is consistent with the mutation rate of DNA replication + repair, suggesting that it is the dominant form of mutation. This mutation rate is based on the number of nucleotides replicated. What this means is that the rate of mutation in functional DNA is independent of how much other DNA is being replicated. Excess DNA offers no protection from the spontaneous error rate of DNA replication.

THEME

Genomes & Junk DNA
However, the protection hypothesis may be applicable to other kinds of mutation such as those caused by chemicals or ionizing radiation. In multicellular organisms such as animals, fungi, and plants, this possible protection may prolong the lifetime of somatic cells or prevent them from becoming deregulated (e.g., cancer).

The idea is that excess DNA may shield the functional DNA from the effects of these mutagens but this would only work if the excess DNA was specifically organized so that it surrounded the functional DNA and provided physical shielding. There's no evidence that this is the case and, furthermore, it doesn't make much sense. The functional DNA in a nucleus is already shielded by lots of proteins, lipids and membranes so it's unlikely that a bit more DNA is going to make a difference.

Not only that, but some kinds of DNA damage caused by these mutagens will cause strand breakage. What does that mean? It means that the larger the genome the greater the chance that damage will occur. In other words, excess DNA leads to greater rates of mutation, not lower rates of mutation, for those types of mutagens. Ryan Gregory shows results from several studies during the 1970s that establish that fact.

I sympathize with Ryan's call for experimental support of the hypothesis but I'd also like to point out that not only does it not have direct evidence to back it up but it's not even theoretically feasible. It's just a bad hypothesis based largely on a misunderstanding of mutations and how they arise.

Also, the protection hypothesis doesn't pass The Onion Test which is one of the first requirements for an adaptive explanation of junk DNA.


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