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Sunday, December 27, 2009

Epigenetics affect specific genetic segments and is personalized


This is quite interesting: A. Feinberg and R. Irizarry, from John Hopkins University (Maryland, USA), have been researching epigenetics in mice and found some curious implications, not known before.


Rapid adaptation to changing environmental conditions (new disease variants, for example) can hardly be achieved by mere genetic change, which is just too slow. Similarly, genes that cause certain diseases (like schizophrenia or diabetes) are also proving virtually impossible to find (as natural selection would wipe them out).

Epigenetics offers potentially alternative explanations to such crucial problems in the field of genetics. However it is a very new field and it is unclear how inheritable are such modifications.

Feinberg and Irizarry have found with their research that epigenetic modifications (methylation, etc.) affect certain specific batches of genes, more open to such environmental modification, but not the rest (these regions were also found to be the same in humans). They also found that mice with the same upbringing had different individual methylation patterns in some regions, specifically regions that are responsible for anatomy in early development (goodbye anthropometry?)

The Maryland scientists also modelled in a computer simulation a hypothetical variable Y component within an equally hypothetical population. When the environment was stable, this variable Y factor was detrimental to survivality but, when it changed periodically (as happens in reality), it favored the survivality by creating indivduals with a wider range of characteristics.

This variability, biologically implemented by epigenetic mechanisms, seems able to explain a good deal of the otherwise unexplained variability in humans and other animals, both for good and bad.

Read more at Science Daily. Not sure if the paper might be this one or is still in preparation.

24 comments:

Ken said...

Epigenitics would presumably be altering the animal in ways that improved fitness in a certain enviroment: a lack of food leads that persons children to have a human thrifty genotype ideal to cope with famine.

If the food supply increases in the time to the next generation the offspring with a thrifty metabolism suffers ilnesses such as diabetes which would have been prevented by a "squandering" phenotype.

I'm not sure if there is any environment where schizophrenia spectrum disorders could increase fitness though.

Maju said...

Genetics and epigenetics seem to work the same random way, only that epigenetics is much quicker.

Let's say that you throw a dice and 6 max. fitness and 1 max. unfitness. A genetic mutation in this example could have all 6 variants but only those that do provide at least some fitness survive in the long run. There would be a tendency to get fixated at the value 6, because it's the one that maximizes fitness.

But the environment is not constant: it changes, largely because the adaptation of other hostile species or because of climatic fluctuations or because of change of habits in a population (this last would be more typical of humans). And here comes epigenetics to the rescue: to respond in the short term to such challenges.

So epigenetics throws another dice and those with value 6 have improved whatever that allows them to survive and reproduce in the new environment and those who get a 1 become schizophrenics, diabetics, etc. (or have greater chances of it). From the viewpoint of the family, the ethnos and the species, the survival of one or several is better than the death of all, so makes perfect sense. Of course the survival of all is optimal but in a changing environment diversity is in fact optimal, even if some extreme cases are not, because diversity allows some to survive, while lack of it will eventually sentence all to extinction.

That's why sex exists in fact: asexual reproduction is possible but does not grant enough diversity, so in the long run it tends to disappear.

Ken said...

The arguments that schizophrenia is a advantagous trait gone wrong, in excess, or in the wrong environment are the only possible explainations, unless it's some kind of bug INFECTIOUS CAUSATION OF DISEASE:AN EVOLUTIONARY PERSPECTIVE.

The modern Western situation where there is all you can eat all year round for a very long life(>70) must have been vanishingly rare in evolutionary time. It's easy to see how that could cause illnesses like type 2 diabetes.

Still not sure about schizipheria though.

Maju said...

I'm not sure either, but it's very possible that whatever gene or epigenetically modified gene induces schzophrenia also has a an alternate state that gives some adaptative advantages, so when dice is rolled, some get the good and some the bad.

However the research is not focused specifically in this disease and just mentions it, along as autism, as possibly induced by epigenetics and not simple Mendelian genetics.

It may well be the case that it is actually triggered by other factors such as medicalized birth or whatever else. Or even that it is not a single disease but many different ones.

terryt said...

Perhaps epigenetics can induce genetic mutations, even if it cannot influence the suitability of a particular mutation. But merely increasing the number of mutations in a particular region of the chromosome would increase the chance of beneficial ones.

That would explain why mutations that increase production in domestic animals is so difficult to achieve yet mutations that increase survivabilty seem relatively frequent.

Maju said...

I don't think there's any reason to think that epigenetic phenomena do that.

I also don't see the logic of your reasoning. Viable mutations should increase survivability: you as herder are operating on the existing gene pool of a species that existed long before being domesticated, for whom your concept of "productivity" just makes no sense.

But whatever the case I can't see any correlation with epigenetics.

However genetics surely works in a similar (even if independent) way to epigenetics: mutations are random, not directional. Directionality is only achieved by selection on pre-existing gene diversity (but if pressures change, so does the direction of selection, whether on genes or epigenetic modificiations).

terryt said...

'you as herder are operating on the existing gene pool of a species that existed long before being domesticated"

Most certainly not true. Many mutations have occurred since domestication. Wool on sheep instead of hair is one I immediately think of. Many genes involved in milk production are also almost certainly post domestication. Scientists are continually seeking new mutations so they can breed from individuals with them.

"Directionality is only achieved by selection on pre-existing gene diversity"

Mutations are occurring all the time. Most are disadvantageous but some are not. Your own article suggests that epigenetics increases the mutation rate at certain sites so I can't see what you don't understand about the process. Quote:

"Feinberg and Irizarry have found with their research that epigenetic modifications (methylation, etc.) affect certain specific batches of genes, more open to such environmental modification, but not the rest"

Maju said...

Most certainly not true. Many mutations have occurred since domestication. Wool on sheep instead of hair is one I immediately think of.

I'm not an expert but I recall reading about sheep having already some wool on their heads before domestication, so what has been selected for is a variant of that.

Many genes involved in milk production are also almost certainly post domestication.

Mostly just selecting the best milk producers from a pre-existing gene pool. They are mammals, you know.

Scientists are continually seeking new mutations so they can breed from individuals with them.

But scientific intervention in breeding is a very recent development. Historically it was mostly a matter that farmers handled themselves the best they could.

Mutations are occurring all the time. Most are disadvantageous but some are not.

True but I'd emphasize that most are disadvantageous or trivial, only very rare ones would be really advantageous, specially from the viewpoint of the farmer, who has some quite narrow interests.

Your own article suggests that epigenetics increases the mutation rate at certain sites so I can't see what you don't understand about the process. Quote:

"Feinberg and Irizarry have found with their research that epigenetic modifications (methylation, etc.) affect certain specific batches of genes, more open to such environmental modification, but not the rest"
.

That says what it says: that some batches of genes are open to epigenetic modification while others are not, it seems. Epigenetic modification is not the same as a genetic mutation: the base chain remains the same through methylation or other similar alterations. In principle epigenetics only affect the individual though there was recently some talk that some epigenetic changes could be inheritable to some extent (but in any case it's not the same as altering the gene like in C->T or whatever).

terryt said...

"But scientific intervention in breeding is a very recent development".

So the difference between humans and other apes is simply a result of diversification 'from a pre-existing gene pool"?

Maju said...

Not sure how that relates with the quoted text but to some extent yes: humans, chimps, etc. are variants of that common ancestor.

Mostly the process seems to happen through the accumulation of "trivial" or quasi-trivial mutations, that are more or less equivalent in fitness but different in effect. Is it better to have curly or straight hair? I'd say it's mostly trivial but different. Is it better to be specialized in fruits like chimps or roots like gorillas? Depends.

Obviously the other surviving apes are perfectly fit, so it's not a matter of increased fitness leading to something but of more or less erratic changes that, when clearly harmful are selected against and that in some cases happen to open new possibilities, maybe at some point leading to an increased fitness for certain conditions.

Because fitness is not an absolute value but a relative one: it depends of context a lot.

However if among certain already existing variants, one or several are clearly better for certain conditions, these will be selected for with more or less speed. But only as long those conditions prevail and where they exist.

That's why diversity is so important and why pathways leading to increased diversity generally add improved fitness overall for the species or population. Because they provide enough tools to confront a wide array of potential situations.

terryt said...

"so what has been selected for is a variant of that".

If you believe animal breeding is as simple as that why don't you take up a job in that field?

"only very rare ones would be really advantageous, specially from the viewpoint of the farmer"

And that's why epigenetics doesn't work for the genes farmers are interested in. Those genes do not help the individual survive, except statistically under artificial conditions. Whereas in 'natural' conditions epigenetics and genetics would work in harmony.

Your latest post sums things up very well.

Maju said...

If you believe animal breeding is as simple as that why don't you take up a job in that field? -

If you believe that getting a job in Europe is so easy why don't you migrate here? WTF!

And that's why epigenetics doesn't work for the genes farmers are interested in.

Do I look like if I care at all. I'm interested in genetics as such, not in stock breeding.

Those genes do not help the individual survive...

Epigenetic alterations allow more individuals to survive in the short run when faced with environmental changes, borrowing precious time for the much slower genetic adaptations to evolve if the change happens to persist or just for further epigenetic-only (or mostly) adaptation as conditions change again.

It is a well known fact in evolution that specialists are doomed, that only generalists survive in the long run. Epigenetics (and diversity in general) allows for such a broader scope at the biomolecular level.

terryt said...

"If you believe that getting a job in Europe is so easy why don't you migrate here?"

If animal and plant breeding was as simple in Europe as you believe I would.

"Do I look like if I care at all. I'm interested in genetics as such, not in stock breeding".

That's why you know very little about practical genetics. Stock breeding and evolution have a great deal in common.

"borrowing precious time for the much slower genetic adaptations to evolve if the change happens to persist"

And the paper says that genetic change is increased in parts of the chromosome that would aid this survival, allowing greater chance of advantageous mutations. Actually some such process has been suspected by animal breeders for some time.

Maju said...

"And the paper says that genetic change is increased in parts of the chromosome that would aid this survival"...

The paper is behind paywall for what I know but the news article does NOT say that. It says that epigenetic change (which is always rapid) is what actually aids survival by increasing phenotype diversity even in closely related individuals.

terryt said...

"Feinberg and Irizarry have found with their research that epigenetic modifications (methylation, etc.) affect certain specific batches of genes, more open to such environmental modification, but not the rest"

Maju said...

Exactly! The genes are methylated (epigenetics) not mutated (genetics). I know what I wrote myself and what it means, please!

terryt said...

One of the effects of methylation is mutation:

http://carcin.oxfordjournals.org/cgi/reprint/18/5/869.pdf

Maju said...

It's an old paper (1997). I noticed first not because of the date as such but because of this:

"The only naturally occurring modification of DNA in higher eukaryotes is the methylation of the 5 position of cytosine (C) leading to the formation of 5-methylcytosine (5-mC)".

Today it is known that many other epigenetic alterations happen in fact.

While looks like a pioneering paper in epigenetics, I suspect that is very much obsolete by now.

terryt said...

"Today it is known that many other epigenetic alterations happen in fact".

That doesn't alter the fact that methylation causes mutations. It makes sense that epigenetics has an effect on genetic makeup. We know that evolution is not entirely random. In fact it is usually directional. Once a species or group of species starts evolving in a particular direction change can become quite rapid. Epigenetics, and the subsequent mutations, provide a possible explanation for how this comes about.

Maju said...

I haven't read anything like that anywhere else in spite of my vivid interest for epigenetics. So I choose to put it on hold unless further studies confirm this claim.

However I do recall now another study that suggested that gibbon divergence might have been mediated by epigenetic factors.

So, well, we'll see.

terryt said...

Thanks for the link.

"So, well, we'll see".

Yes. We await similar research for other species. I'm sure it will indicate similar phenomena.

Ken said...

Epigenetics: Feast, Famine, and Fatness.

"In the last five to ten years, there has been more and more evidence showing there is a non-genetic part that can be passed down to children and even grandchildren. As of this summer there are over 100 scientific articles documenting non-DNA inheritance, also called transgenerational epigenetics."

Maju said...

Yah... but for how long? Wouldn't the methylation or whatever other epigenetic change be eventually erased and the genome returned to the normal stage. How? I'm really intrigued.

terryt said...

"Wouldn't the methylation or whatever other epigenetic change be eventually erased and the genome returned to the normal stage".

Maybe. But an agricultural geneticist I corresponded with some years ago mentioned research that suggested that mutations were not completely random. They seemed to occur under some generational influence. He suggested epigenetics may be the explanation. In which case the epigenetic change you're talking about may become replaced by a genetic change before it is erased.