## Wednesday, August 07, 2013

### Ostragene: realtime evolution in a dirty city

Ostrava, an industrial hub in the Northeast of the Czech Republic, is the country's third largest city (300,000). It's full of coal mines and steel mills. ArcelorMittal is the world's largest steel producer and bought a major facility there. The air contains products of a chemical plant and some junk blown from the nearby Poland, too. The history of hardcore pollution in the region goes back to the 19th century.

Just to be sure, we're talking about real toxins, not bogus pollution like CO2. The air often contains things like benzo(a)pyrene, a carcinogenic polycyclic aromatic hydrocarbon, in concentrations severely (e.g. by 700%) exceeding the allowed maxima.

Yesterday I learned something I should have heard about in late 2011 but I had to miss it. But let me get to the point. One should expect that with this much benzo(a)pyrene, people in Ostrava will get many more tumors than those in Prague, for example. But they didn't. The life expectancy seems to be a bit lower in Ostrava but this difference seems to be associated with cardiovascular diseases. A paradox.

The first word in the title leaked the resolution to the paradox. Many/most people in Ostrava developed a special mutation of a gene whose task is the correction of errors in the DNA. The gene used to be known as XRCC5. The Ostrava folks carry a more active version of this gene.

This mutation seems a bit comical, like a Nature's clever and witty trick, and the idea of such a mutation closely resembles the theme of the 1988 movie by later famous film director Mr Jan Svěrák, The Oil Gobblers (3 parts), about a new (fictitious) species that evolved in dirty environments and that really loves to drink and eat petroleum and various other yummy things.

The idea of such a mutation may sound funny but Nature seriously works like that!

The mutation has some negative side effects – it makes one's aging process a bit faster and may speed up the cardiovascular diseases which is why the people with this mutated gene have a lower life expectancy, by about 2 years, but this is probably still a smaller reduction of the life expectancy than what the benzo(a)pyrene would steal from an unmutated human being.

You will probably agree that XRCC5 isn't a catchy name. Well-known Czechia's songmaker Mr Jaromír Nohavica who lives in the region and possibly has the mutation as well has invented a more colorful name for the mutation – Ostragene (in Czech, it's simply "Ostragen"). Needless to say, this word constructed by the combination of the words "Ostrava" and "gene" sounds sexy also because it is so similar to "estrogen". The poet was successful and everyone, including the medical experts, began to use this terminology.

A few years ago, I was lucky to be in Nice and to hear the world's leading defenders of the Intelligent Design paradigm advocating their framework to explain the origin of species – well, mostly their criticisms of Darwin's theory. As you can guess, I ultimately thought that every single criticism had a bug, perhaps the very specific bug that I saw in them, but you may be sure that their knowledge of the species was impressive and the arguments were rather sophisticated.

Some of the arguments against evolution dealt with the speed of mutations - see also an old TRF interview with Franziska Michor. As far as I could say, the argument was almost perfect but it did contain a wrong assumption or oversimplification that was needed for the argument to go through, namely that the speed of mutations is dictated "from above" and may be predetermined by the author of the argument. In reality, even the speed of mutations is something that depends on your DNA and Nature is trying various experiments to help the (mutated) species survive in the given environment. This includes Ostrava-like suppression of the mutation rate whenever it seems like the frequent mutations are "forced upon the organisms" by the environment but they're not helpful to adapt to changes because the environment is nearly constant; and on the contrary, Nature may prefer mutations and organisms with a faster mutation rate whenever it seems like they need to adapt quickly and it's a better idea to try many mutations – Nature's individual experiments.

While I have mentioned top creationists as those who overlook the dynamical character of the mutation rate, it's really the environmentalists who are making this mistake – and many other mistakes – most frequently. Quite generally, they underestimate if not completely deny Nature's ability to adapt.

If someone understands evolution at the technical level, I would love him or her to explain to me how long a time it takes for a mutation like Ostragene to conquer much of the city. The original mutation had to be pretty random – i.e. unaffected by the environment, right? So it must have been due to the environmental pressures that the mutation started to spread in Ostrava and not in Prague, for example, am I right? Otherwise we would be back to the flawed Lamarckian evolution, I guess.

1. could you please provide the reference to the study you are discussing here?

if it is this one, http://www.sciencedirect.com/science/article/pii/S0027510711001424

there appear to be no evidence of any mutation in XRCC5 in this paper

2. Dear Anton, I haven't seen a study yet, I am trusting newspaper articles and I am ready that something important is completely misleading in them.

At any rate, a more up-to-date paper by a similar group of authors is

http://mutage.oxfordjournals.org/content/28/1/89.short

which surely finds an effect although they don't seem to link it to XRCC5 as far as I can see,

3. For a gene to go to near fixation in just a few generations there would have to have been a tremendous death rate for those who didn't have it. And they had to die before they could breed. I am frankly skeptical.

4. Thinking SkeptikAug 7, 2013, 8:50:00 PM

I fear that you fall into the deeper trap set by Lysenko (who was ably assisted someone by your country may remember with less than affection - Josif Vissarionovich Djugashvili - the 'Man of Steel').

Darwinian evolution is based upon (nay, requires!) the 'survival of the fittest'. lukelea has it right. Many deaths (without, or with only minimal, breeding) are required for the gene to 'spread' to the whole population. This is usually achievable only over many generations.

5. Thinking SkeptikAug 7, 2013, 8:56:00 PM

Lysenko.

6. hi lubos,

thanks for the links. as far as i can gather, no mapping of any mutations in those papers.

as also suggested by lukelea, any mutation would require a much longer time period to be fixed in a population, unless the majority of ostrava inhabitants are direct descendants of one/few people that first acquired the putative mutation.

would be interesting to test for direct impact of the environment on XRCC5 expression. there are probably enough ostrava natives living in other cities, and vice-versa, people born in less polluted areas that moved to ostrava recently. it is one thing to state that ostrava natives carry a mutation responsible for higher XRCC5 expression. completely different alternative is that any person placed in ostrava would begin to express more XRCC5.

the simplest experiment to address your question of mutation in XRCC5 or elsewhere is to sequence and compare the genomes of ostrava inhabitants with people living in less polluted regions.

7. I agree with you. It is a nonsense that any mutation could spread so quickly over the whole population of city. Nature can adapt but it takes much longer.

I suspect that what is meant is actually epigenetics. Various genes can be switched on or off by a process of methylation of DNA. It can be that some environmental stressors cause an epigenetic change in the gene so that it is more frequently expressed and more DNA ligase is produced

http://en.wikipedia.org/wiki/DNA_repair#DNA_repair_mechanisms

The epigenetics is pretty fascinating stuff. It is even researched as a possible cause for psychiatric disorders. For a nice documentary see

8. Right, I have the same concerns about the claims. But could you be more quantitative? The air has sucked in Ostrava for 150 years or so. There have surely been many deaths in the past. What can one get here?

9. How does this epigenetics work? The papers show that the Prague people don't react in this way. How and when in the life cycle does the increased expression of the gene is switched on?

10. I encourage you to watch the video. I explains that there are certain critical phases in the lifes of man, when the outer stressor can be imprinted upon the DNA. And what is even more interesting, these critical phases are different for males and females. It can be that the people of Ostava experienced some common stressor in the passed and it was passed to current generation. The same stressor did not act in Prague. I am only guessing, I didnt read the study
And yes, it is a form of Lamarckism, although more limited than original ideas of Lamarck. Epigenetics is a form of an adaptive mechanism.

11. I know nothing of biology and apologize in advance if my question is stupid: is it possible for the mutations to occur in viruses instead (so perhaps at a much higher rate than in their hosts), and then could some of the evolved DNA be transferred to the host?

12. Unless I am mistaken genes are switched on and off all the time by the environment. That is fundamentally what happens when, for instance, you get hungry, to take a trivial example.

13. RA Fisher in his book on The Genetical Theory of Natural Selection does the math. As a rule in a large interbreeding population the chances for even highly favorable mutations (which are rare) going to fixity is very small. On the order of one chance out of fifty if memory serves. Which means that on average the same mutation has to occur many times before it takes. Also it takes many generations for fixity to be achieved. Hundreds if not thousands or more.

14. Contra Lysenko, those changes are not handed down. They are just the genome doing its thing. See those lectures of Systems Biology i linked to, starting with the second one.

15. Genes are activated by environmental conditions.

A similar protective gene activation is that of radiation hormesis under low levels of ionising radiation that seems to increase the quality of checking that the new DNA from mytosis has been "correct". If the check fails, then the split chain is "killed" and the proteins reabsorbed within the cell for another try.

It's like adding extra bits of "checksum" when making copies of data. With fewer "bits of checksum", cells can divide more quickly and easily and with less effort, but the rate of mutations is higher under conditions that have the potential to be disruptive to making good copies.

I suspect that there are many latent genes in evolved species, inherited from ancestors that lived in what would now be an alien world to us, when survival strategies worked better.

Natural selection isn't "survival of the fittest"; it's "survival of the most adaptable".

16. For the sake of completness, I would add that genes are switched off or on also in the process of cell differentiation. Why is the liver cell different from a nerve cell? It is because each cell has different set of genes switched on. The switching off and on of genes is relativitely poorly understood. If you wound your arm, in the process of healing, certain genes in the mesenchymal pluripotent stem cells will be switched on to produce new tissue etc. So the switching on and off of genes goes on all the time in the body.
In epigenetics it happens in the ovum or the sperm and the change is transmitted to following generations. But it is still poorly understood.

17. Maybe 7 (or so) generations ago one person with this polution-managing gene/mutation moved to or was born in this city and is someone to whom a significant portion of the city's population can trace their lineage back to?
Another, compatible but slightly SPECULATIVE, idea is that the mutation in question might be pleiotropic to the effect of making the carriers feel cozy and more than normally comfortable in dirty smoggy urban environments? [Not necessarily just something to smirk at. ;-)]

18. I think it's probably just a happy coincidence.

Young mortality rate should be absolutely huge for there selection in as few generations. As has already been said.

Concerning the epigenetic hypothesis in some comments: I think epigenetics is a marginal phenomenon and often exaggerated. If this case was epigenetics would be a revolutionary discovery.

19. Another mechanism for the effect would be hormesis:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2248601/

20. I think it's much more likely that carcinogenesis isn't linear. The animal studies used to derive safe thresholds all used massive amounts of carcinogens, and the safe thresholds are derived by linear extrapolation. But there may be biological gene repair mechanisms which deal (moderately well) with low doses of carcinogens and break down with high doses. Of course, it might not work this way with all chemicals ... so it's best to use the linear extrapolation in setting the safe dosage.

21. Dear Peter, what you - and perhaps also Gordon and others - completely overlook is that the research concluded (see the last sentence of the abstract below)

http://mutage.oxfordjournals.org/content/28/1/89.short

that the bodies from Ostrava react *differently* than bodies from Prague. So this observation is *not* just about Ostrava's folks doing OK. It is about a diffferent behavior of their bodies.