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I'm not strong in biology, so bear with me on this:

I've been reading that as we age, our DNA is damaged by internal (e.g. errors during replication) and external (e.g. sun damage or radiation) factors.

  • If you take, say, an 80 year old, can you find DNA in their body that's the same as when they were a newborn? What kind of cells would have undamaged DNA?

  • Is DNA damage distributed evenly across the body or will some parts have more damage than others?

  • Is there any published data on how much DNA damage an average person accumulates over their lifetime? I'm not sure how this can be quantified, but I'm wondering if there has been any study on gauging damage.

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    $\begingroup$ Since errors frequently occur during cell division, I guess cells that divide less frequently (e.g. mature neurons do not divide at all) will probably have less damage. Some cells not only divide fast, but also become polypoloid (e.g. liver cells), so these cells probably can tolerate a lot of mutations. $\endgroup$ – Sergei Mar 13 '15 at 4:00
  • $\begingroup$ Also, this new article may be of interest DNA mutation clock proves tough to set. Apparently, rates with which mutations accumulate over human generations may be fluctuating! $\endgroup$ – Sergei Mar 13 '15 at 20:29
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Excellent question!

  1. You would definitely be able to find quite a few sequences of DNA that are undamaged (in fact most of them would be undamaged), but it is very unlikely that any cells in his/her body would have a perfect copy of the entire original genome.

  2. I'm sure that cells closer to the skin (exposed to more radiation) would have more mutations, but beyond that most everything depends on where you live, your habits, etc. (if you're a smoker you will obviously have more mutations in your lung cells).

  3. Under regular circumstances (low levels of mutagens), about 3 nucleotide mutations occur in the human genome per cell per division (DNA replication) (from http://www.ncbi.nlm.nih.gov/books/NBK26881/). The rest of the math would be a very rough estimate, seeing as you'd need to make a lot of assumptions (cell division rate average, other mutagens an organism may encounter, life span, the list goes on), but however you want to do it, there's the number you need to start with.

I hope this helps.

CDB

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  • $\begingroup$ Hi. Thanks for your answer. Regarding the first question, is it possible to use multiple DNA samples and compare them to one another to derive the entire original genome? The goal would be to identify damaged sequences and replace them with the undamaged ones from other samples since I assume a single block of DNA is unlikely to be corrupt in every single sample. I think a similar concept is implemented in cryptography and data storage in computers to achieve integrity. $\endgroup$ – Mark13426 Mar 13 '15 at 2:41
  • $\begingroup$ @Mark13426 Sure. See e.g. this PLoS Computational Biology paper and references therein. Often the aim in these studies is to map cell lineages rather than infer the genotype of the fertilized egg, but the information is there if you wanted to do it. $\endgroup$ – Corvus Mar 13 '15 at 2:59
  • $\begingroup$ I'm not sure how you would identify which sequences were the original, undamaged sequences unless you had a reference (such as a map of the organism's genome when it was an embryo), but it would be very possible to retrieve an entire complete and undamaged genome from perhaps only a few hundred cells if you could identify the original DNA. May I ask what your project is regarding? It sounds very fascinating! $\endgroup$ – CDB Mar 13 '15 at 3:00
  • $\begingroup$ @CDB It's not generally true that cells closer to the skin have more mutations; what matters more than e.g. UV exposure is the number of cell generations that a cell goes through. Intestinal epithelium turns over rapidly and can have up to an order of magnitude greater number of cell generations than other tissues, resulting in a higher number of accumulated mutations over the lifetime. $\endgroup$ – Corvus Mar 13 '15 at 3:02
  • $\begingroup$ Very true, however skin cells would be much more prone to mutations from radiation and radiation is a much more deadly mutagen than just mistakes made inside the cell itself seeing as radiation actually destroys the nucleotide. $\endgroup$ – CDB Mar 13 '15 at 3:07
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You've asked a number of questions here, but yes -- mutation rates have been studied extensively in humans as well as in model organisms. And as you suggest, they vary substantially across tissues. One starting point to read about how mutation rates are measured and how they vary across species, tissues, etc., is a 2010 Trends in Genetics review by Mike Lynch. See particularly Table 1.

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