Which Sections of DNA Are Most Prone to Mutations?

[dmehling]

Can someone give me a non-technical explanation of a mutational hotspot? What exactly is it and what causes it?

 

[Pythagorean]

I found a detailed article that doesn't use a bunch of jargon. It gives a basic overview of mutations and then hotspots:

Igor B. Rogozin, Youri I. Pavlov, Theoretical analysis of mutation hotspots and their DNA sequence context specificity, Mutation Research/Reviews in Mutation Research, Volume 544, Issue 1, September 2003, Pages 65-85, ISSN 1383-5742, 10.1016/S1383-5742(03)00032-2.
(http://www.sciencedirect.com/science/article/pii/S1383574203000322)
Keywords: DNA sequence context; Classification analysis; Mutable motif; Microsatellite; Hotspot; Direct repeat; Palindrome; Oligonucleotides; Mutation spectra

 

[Pythagorean]

It looks like the cause is still an open question:

"Thus, study of mutation hotspots can help reveal mutagenic mechanisms, or can reveal information about the functional domains of a target protein [16], [39], [40], [41] and [42]. Some mutation hotspots are thought to depend on the nucleotide sequence and the mechanism of mutagenesis per se; these hotspots are called intrinsic mutation hotspots. In contrast, some hotspots may be due to preferential expansions of mutants with high fitness [41] and [42], e.g. some hotspots of somatic mutations in functional immunoglobulin genes [43]. It has been suggested that hotspots in human p53 reflect both intrinsic mutability and selection for tumorogenesis [41] and [44]. This article discusses primarily methods that are useful for analysis of intrinsic mutation hotspots."

 

[dmehling]

Thanks for the article, although it's not exactly what I had in mind. Still rather technical and you have to pay to read the entire article.

 

[Pythagorean]

ah, my apologies, I must have inadvertently had access from my university. I thought it was open access.

Do you the kinds of mutations that can happen and what exactly a mutation is?

 

[dmehling]

I have a basic understanding of the different types: substitution, deletion, insertion, gene duplication, genome duplication. That's about all I really know at this point.

 

[bobze]

I have a basic understanding of the different types: substitution, deletion, insertion, gene duplication, genome duplication. That's about all I really know at this point.

Think about it like this. Suppose we had a football field (a proper football field, not a soccer field :P), 100 yards measured off. Every 10 yards we have a long horizontal line that cross the field.

Going on how most people think of mutation (which isn't necessarily a bad thing when you are just learning biology) you would expect that a mutation could happen in any of the 10 yard intervals equally likely.

But when we actually look at mutations, we don't see that. We see them coming out "clumpy". No to make the analogy weird. Suppose we had some some sections of the field under some strange gravitational anomaly, that those 10 yards were still 10 yards but when viewed from a birds eye view were "smaller" than other, "uninfluenced" sections of field. Now if you flying over in a jet trying to drop a bowling ball on the field, where is it more likely to hit? Obviously in our "uninfluenced sections" of field.

So in the analogy, we use gravity to alter the chances that mutation (the bowling ball) can affect an area of the field. In real life, something similar happens. DNA isn't just sitting about in a cell laid out nice and neat like a football field. It has structure unto itself. Through proteins (things like histones) which alter the packaging of DNA, but in the actual distribution of electrostatic charges as well--Or the "gravity" in our analogy. So the structure and nature of DNA (how it exists in cells) causes some areas to be more amendable to mutation than others.

Did that analogy help at all or make it worse ?

 

[dmehling]

Thanks for your creative analogy. I think it does help illustrate the concept.

Which sections of DNA are most susceptible to mutations and what structural features of such sections render them more susceptible?