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Epigenetics- exploring


Michaelangelica

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I would like to briefly look at multicellular differentiation, such as occurs within the human body. All these cells contain the same DNA, yet each cell type, uses a differentiated aspect of the genes, to define its unique characteristics. With a very broad stroke of the brush, each differentiation of the DNA reflects a unique DNA configurational entropy. This configurational entropy reflects the packing/unpacking, activity, etc., which in this analysis, is related to the entropy generated by the straw that stirs the drink. As such, one would expect different amounts of mitochondria in the various cell differentiations, which turns out to be the case.

 

Let us look at one important cell differentiation; neurons. After a certain point, these cells no longer replicate. Relative to this discussion, this implies an upper limit is reached for the genetic configurational entropy within the neuron, which is not able to put the neuron over the entropy hump, needed for a cell cycle. This is related to neuron firing, which reverses the entropy potential of the cell membrane, by allowing the pumped cations to better approach the low entropy of a uniform solution.

 

Neuron firing is another path for the second law, but its impact is different compare to active transport. Neuron firing does not feed the mitochondria, in quite same way, as the chemical potential within transported chemicals. Neuron firing means work with less influx of chemical energy. If neurons were not designed to fire, the molecular input would be higher, better feeding the needs of the mitochondria with chemical input. Getting over the hump would allow neurons to replicate.

 

Neurotransmitters, which are connected to firing, are designed to be inefficient, with respect to using the potential within the cationic gradient. In other words, it should only take a little energy to transport anything, but these are designed to waste energy at the membrane. Other neurotransmitters will increase membrane efficiency, making it harder for the membrane to fire and waste energy. These better serve the needs of the mitochondria, by maintaining membrane potential.

 

Based on neurons not replicating, the balance of the neurotransmitters favors the entropy of the second law at the membrane, acting via neuron firing, where consciousness is expressed. This firing helps to lower the time average entropy within the neuron. For example, memory that is specific implies fixed chemical structure, that is not subject to many degrees of freedom. Consciousness, via neuron firing, implies less entropy on the inside of the neuron (relative), better allowing changes that can fix memory into low entropy structure. Without the local firing, the opposite occurs, increasing the entropy of internal neuron structures. The memory structure becomes more fluid.

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I would like to add gamete cells to the analysis. The unique change is the halving of the DNA at maturity. This observation suggests, that high entropy is pushing these cells past normal cells cycles.

 

The DNA, as an isolated molecule, is a low entropy configuration. The DNA double helix is a huge double polymer that is very stable and designed to not change very easily. But the DNA is also a template molecule. As we unpack the DNA and induce activity on the DNA, the entropy of this composite configuration (DNA plus everything else) increases. Yet the base DNA molecule remains. This base stability in the DNA makes it like an anchor that limits maximum configurational entropy. One way to get over this entropy hump, is to get rid of part of the anchor.

 

As an analogy of the configurational effect, say I place a cup of sugar into a glass of water. We can stir the drink and dissolve the sugar. But once we reach saturation, no matter how hard you stir, there is always some at the bottom. One way to make sure less remains on the bottom, is not to stir even harder than that, but use less sugar. Halving the DNA is one logical way to get past the impact of the low configurational entropy DNA anchor, while doing no harm to the DNA. We could also fragment the DNA, or add defects along the double helix, but this is more destructive.

 

When we combine the male and female DNA, what appears is a pile of sugar on the bottom of the glass. The entropy tries to stir it away or increase entropy. There is shuffling of genes, which is an entropy push into more degrees of freedom, implicit of blending instead of the original segregation.

 

The observation that the combined male-female DNA is not halved again, sort of implies the entropy potential had dropped slightly. This could be due to the original high entropy needed to half the DNA, being a team effort that requires assistance. The single gamete cells may not be able to generate this level of entropy. They may be designed to hang on, with entropy decaying.

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I would like to add some simple entropy considerations for speciation. With a broad stroke of the pen, creating a new species adds new degrees of freedom. We reach a fork in the road, with more options left and right. Since the straw that stirs the drink is connected to the mitochondria, and the mother is the one who what passes on the mitochondria, this is the logical place to look for the entropy boost.

 

If we compare active genes to junk genes, the active genes have a higher level of configurational entropy, since they offer additional degrees of freedom, such as the production of RNA. This is not to say the junk genes are not important. Their value is within their lower configurational entropy.

 

What this seems to suggest, if the mitochondria increased the entropy within the female gamete cell, a little too high, theoretically, the 1/2 DNA remaining would need to reflect this higher level entropy at equilibrium. Based on active and junk genes, this means the cell would need to retain, within the saved half, more active DNA content, than had been normal for that species. The offspring now has more degrees of freedom. As this DNA entropy gap increases over time, eventually the new species can no longer breed with the former species, since the entropy of the combined DNA is out of whack relative to the next equilibrium steps needed for viability.

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  • 2 weeks later...
I would like to add some simple entropy considerations for speciation. With a broad stroke of the pen, creating a new species adds new degrees of freedom. We reach a fork in the road, with more options left and right. Since the straw that stirs the drink is connected to the mitochondria, and the mother is the one who what passes on the mitochondria, this is the logical place to look for the entropy boost.

 

If we compare active genes to junk genes, the active genes have a higher level of configurational entropy, since they offer additional degrees of freedom, such as the production of RNA. This is not to say the junk genes are not important. Their value is within their lower configurational entropy.

 

What this seems to suggest, if the mitochondria increased the entropy within the female gamete cell, a little too high, theoretically, the 1/2 DNA remaining would need to reflect this higher level entropy at equilibrium. Based on active and junk genes, this means the cell would need to retain, within the saved half, more active DNA content, than had been normal for that species. The offspring now has more degrees of freedom. As this DNA entropy gap increases over time, eventually the new species can no longer breed with the former species, since the entropy of the combined DNA is out of whack relative to the next equilibrium steps needed for viability.

 

Try again. This time, aim for clarity, with supporting evidence.

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Life is more than entropy, with the straw that stirs the drink, increasing degrees of freedom. There is another, opposite side of the coin, connected to ordering principles within the cell. For example, humans have one less chromosome than apes. Relative to apes, humans lost a degree of freedom at the level of chromosomes. We gained additional active genetic content for extra brain functionality, but lost genetic content relative to fur. The sum of the effect is a combination of entropy and order. I overviewed entropy first, since the potential for change was easier to address.

 

I would like now to begin addressing ordering principles. To begin, I would like to look at a hypothetical protein. In this hypothetical situation, the protein is floating in a vacuum and there are no secondary bonding forces such as polar, van der Waals, etc. In this hypothetical state, there are many degrees of freedom with respect to possible ways the protein can bend, fold and blob. As we add the secondary bonding forces, like groups attract like groups, adding order that will lower some of these degrees of freedom. The strongest secondary interactions will have the strongest ordering impact, lowering degrees of freedom, longer even at moderate ambient energies. Entropy needs energy to increase, with stronger secondary bonding needing more energy to break the secondary bonding so additional entropy can take over.

 

Relative to the protein and secondary bonding, hydrogen bonding is up near the top with respect to creating order in chaos, due to bond strength. Relative to our hypothetical protein, hydrogen bonds will wind it into a helix. Protein don't normally have many degrees of freedom relative to the helix, no matter how hard the straw tries to stir the drink. This order is good if we wish to crank up the potential.

 

The next thing I would like to add, to our hypothetical protein with less degrees of freedom is a solvent medium, such as water. Water has the highest melting and boiling points, by a lot, for any solvent with similar molecular weight. The reason this is so, is water can form four hydrogen bonds with other water molecules, two with its hydrogen and two with its oxygen. It is sort of the mini-me of carbon. Other solvent substitutes of equal size and mobility can't form the same strength of secondary bonding as water, such that they can't establish as strong ordering, to help overcome other aspects of protein entropy. Relative to our hypothetical protein, the push and pull from the ordering within water, will further reduce its degrees of freedom, by segregating polar and non-polar groups. Polar organics, are not as discriminatory and will allow more degrees of freedom for our protein. This of itself is not a problem but makes further ordering more difficult.

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I thought it would be nice to have a thread where we could discuss this emerging field and refine our knowledge to it and post new developments (which seem to be happening weekly!)....

 

i thought so too and have been reading & waiting to see it; however all i see in pages now is off-topic babble that is little less than trolling. what a shame michael. what a shame.

 

give 'er another shot though michael, if you have read something new (as if :eek_big: ) because this is a fascinating topic. i got your back mate. :rolleyes:

 

now from what i remember of the show i mentioned in post #2, the epigenetic factor(s) were chemicals on the outside (on the surface?) of the helix, however this sounds entirely different to me? maybe it's just new. ;)

 

New nucleotide could revolutionize epigenetics

...Anyone who studied a little genetics in high school has heard of adenine' date=' thymine, guanine and cytosine – the A,T,G and C that make up the DNA code. But those are not the whole story. The rise of epigenetics in the past decade has drawn attention to a fifth nucleotide, 5-methylcytosine (5-mC), that sometimes replaces cytosine in the famous DNA double helix to regulate which genes are expressed. And now there's a sixth. In experiments to be published online Thursday by Science, researchers reveal an additional character in the mammalian DNA code, opening an entirely new front in epigenetic research. ...[/quote']
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I would suggest moving this topic down two parallel paths, simultaneously. The first path would be as Turtle suggested, talking about epigenetics like the topic initially began. The second parallel path I will develop, as I have. Eventually the two paths will cross and merge as one, with new logic for why.

 

I would like to go back to the discussion of ordering principles, by looking at a blend of oil and water, which we will put into a blender. After we stop the blender, the entropy is maximized, since we have formed, approximately, a uniform solution of oil and water. But it won't take long before the tiny bubbles begin to combine, leading to the eventual separation back into two layers. In this case, the initial high entropy decreases, to a repeatable steady state, because of ordering principles. We can stir the drink hard or soft and order returns the same way each time.

 

The reason this occurs, in the above example, is connected to the first law or the conservation of energy. In this case, the first law is a little stronger than the second law and can place an upper limit on it. The impact of the initial emulsion is to create surface tension and surface energy between the water and oil. The water would like to form more hydrogen bonds, but because it is touching the oil, this becomes much harder to do. The surface energy within the water reflects hydrogen bonds that would like to form and lower energy; conservation of energy. Entropy can only absorb so much of this extra energy potential, with considerable potential energy left over. This extra energy slowly decrease, as the bubbles combine, even if this means lowering entropy. The combined effect of the potential energy and the entropy is called free energy, with the free energy reaching a minimum, when the two layers appear.

 

If you look at combustion or metabolism, where stored energy is given off as heat and the entropy increasing degrees of freedom, via making smaller things, the free energy decrease has both the energy and the entropy moving in a complementary way; benefits both at the same time. This is favorable to both the first and second law. But in the case of the oil/ water emulsion, even though the free energy is decreasing, it occurs with energy potential and entropy opposing each other. The cell makes use of both effects with metabolism favorable to the natural direction of both the first and second law; working as a team.

 

If you have ever bought a lotion for your skin, such as suntan lotion, this is also an emulsion of oil and water, but it stays at high entropy; near uniform solution. This is done by using chemicals that lower the potential energy at the water and oil interface. The effect of these chemicals is to allow water to form its needed hydrogen bonds, lowering the potential energy in the water. The free energy will still attempt to lower, but the energy potential is much lower, such that entropy stays higher longer.

 

If you look at the phospholipids, nature has added the phosphate group to help lower the surface energy at the water-oil interface. Water is able to form hydrogen bonding with the phosphate at the surface. Relative to free energy, this helps to slant it slightly in favor entropy, relative the phosphate not being there. This is sort of the lotion effect, which has been improved by adding other polar organic groups to the membrane. Free energy in water is still in effect, leading to a repeatable steady state ordering.

 

I don't wish to get too long, but I would like to add two quick membrane things, both connected to the impact of sodium and potassium ions in water. Sodium cations will slightly increase the order within water relative to pure water. While potassium cations will slightly decrease the order within water relative to pure water, i.e., slightly favors entropy within the water. This is not a long range effect.

 

The cell pumps sodium out and potassium in, concentrating these cations on either side of the membrane. Besides the entropy potential to form a uniform solution with the cations, there is also a free energy effect within the cell, which can lower if the inside can get rid of the disordering potassium cations, and lets some of the ordering sodium cations enter. Putting aside the enzymes and energy to creates the cationic gradient, once formed there are two complimentary pushes to lower the free energy of the cationic gradient; entropy and water energy both wish to blend the cations.

 

Since the exterior sodium cations creates some extra order in water and potassium creates some extra disorder in water, and since organics tend to create some level of surface tension within water; implicit of aqueous hydrogen bonding disorder, organics are slightly favored in the water on the outside surface, and slightly disfavored in the water on the inside surface. The potential energy of the water will get higher, faster, because of the disordering potassium cations. This is great for food flow being favored by the water to go from out to in. The local reversal of the sodium/potassium, that supplies transport energy, also temporarily makes the local inside water temporarily favorable via the local inputted sodium. But once the sodium is pumped and the potassium comes back, the organic food gets slightly disfavored by the same water on the inside of the local water. This make it less favorable for backing out.

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I would suggest moving this topic down two parallel paths, simultaneously. The first path would be as Turtle suggested, talking about epigenetics like the topic initially began. The second parallel path I will develop, as I have. Eventually the two paths will cross and merge as one, with new logic for why. ...

 

i don't like that. it's the equivalent of combining a novel and calculus book. i am not entirely insensitive to your need & proclivity to write as you do, however it does not properly belong mixed up as you have it with rigorous studies & expositions. we have places for your stuff here in your blog, or alternate theories forum, or philosophy weightroom. i'm not the only one of this opinion, and your continuing this course in the face of communications informing you of the irritation you engender is at the least rude.

 

my pardon michael et al for further keeping this thread from its intended investigation of new scientific developments into epigentics. with a little luck, it will be the last. ~:lol:

 

The new science of epigenetics rewrites the rules of disease, heredity, and identity.

...

Our DNA—specifically the 25,000 genes identified by the Human Genome Project—is now widely regarded as the instruction book for the human body. But genes themselves need instructions for what to do, and where and when to do it. A human liver cell contains the same DNA as a brain cell, yet somehow it knows to code only those proteins needed for the functioning of the liver. Those instructions are found not in the letters of the DNA itself but on it, in an array of chemical markers and switches, known collectively as the epigenome, that lie along the length of the double helix. These epigenetic switches and markers in turn help switch on or off the expression of particular genes. Think of the epigenome as a complex software code, capable of inducing the DNA hardware to manufacture an impressive variety of proteins, cell types, and individuals. ...

 

full article: DNA Is Not Destiny | Genetics | DISCOVER Magazine

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The second way is the addition of methyl groups to the DNA, mostly at CpG sites, to convert cytosine to 5-methylcytosine. 5-Methylcytosine performs much like a regular cytosine, pairing up with a G, so in the next round of cell division it will be replaced with a regular C. However, some areas of genome are methylated heavier than others and highly methylated areas tend to be transcriptionally less active, through a mechanism not fully understood.
Wikipedia; epigentics.

 

Let me offer an explanation.

 

The processing of the genetic information within DNA is facilitated by highly discriminatory and strong protein binding. It has been shown that the interfacial water molecules can serve as 'hydration fingerprints' of a given DNA sequence [889]. The major driving force for the specificity is the entropy increase due to the release of bound water molecules (estimated at 3.6 kJ mol-1 for minor groove water and 2.3 kJ mol-1 for major groove water, both at 300 K

 

M. Fuxreiter, M. Mezei, I. Simon and R. Osman, Interfacial water as a "hydration fingerprint" in the non-cognate complex of BamHI, Biophys. J. 89 (2005) 903-911.

 

For example, about 110 water molecules are released on binding of the restriction endonuclease EcoRI to its site GAATTC leaving an essentially dry interface and firmly bound complex (with binding constant ~10,000 times that for nonspecific binding), whereas changing just one base out of the recognition sequence leaves those water molecules mostly unaffected and only little different from EcoRI non-specifically binding to DNA [1176b]. Thus, the key to the formation of specific links between proteins and DNA is that the interfacial water molecules allow the protein facile movement along the binding cleft whilst retaining contact information [1443].

 

N. Y. Sidorova and D. C. Rau, Differences between EcoRI nonspecific and ‘‘Star’’ sequence complexes revealed by osmotic stress, Biophys. J. 87 (2004) 2564-2576;

 

Below shows the water that hydrogen bonds to the DNA, found within the major and minor grooves of the DNA double helix. In the case of methylation, the #5 position of cytosine, gets a methyl group to replace the hydrogen. This methyl group causes local surface tension with the water that is bound to -NH2 at position 4. The net result is the finger print changes for binding factors.

 

 

In the case of restriction endonuclease EcoRI, changing one base lowers selectivity by about 10,000 times. I would guess the effect of a single methylation is lower that this, since we are not changing the entire base cytosine, just a methyl tweak. This allows the cell to adjust the binding selectivity on genes, by adding one or more methyl groups in the same region. We can slow down binding rate or switch off binding complexes, depending on the degree of methylation.

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  • 3 weeks later...

The following is a theory which might be a place for further investigation. It is a logical extrapolation of epigenetics, stemming from my last post.

 

Epigenetics does not change the base sequence of the DNA, but chemically modifies the DNA and/or packing proteins, altering the genetic response. Picture the situation where an animal begins to eat a new food, which chemically induces an epigenetic change. These changes might persist for several generations.

 

What I would like to add is the brain and its natural learning capacity. If this scenario, the offspring inherit the epigenetic change. The learning capacity of their brain reinforces the eating behavior, by being taught or by copying the mother. This resets the epigenetic clock to zero, since the same chemical input reinforces the inherited epigenetic change. Now the epigenetic change can linger for an additional generation.

 

The next question becomes, could a reinforced epigenetic change, due to learning the behavior, that caused the original epigenetic change, that lingers over long periods of time, eventually increase the odds of a genetic change on the DNA?

 

One way this might be possible is connected to the aqueous finger print of the altered epigenetic bases on the DNA. It has been demonstrated altering the aqueous finger print, by changing bases, can alter the binding selectivity of enzymes up to 50,000 fold. Could a persistent epigenetic modification alter the binding rates of specific base pairing; much smaller level?

 

As a loose analogy, in a dehydrated state, we have the ideal fingerprints for bases 1,2,3,4. Could an epigenetic change tweak the ideal base fingerprints, making the bases look something like 1.13, 2.051, 2.987, 3.98. One expected effect, would be all the DNA will not change at the same rate.

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  • 1 year later...

Date: 2011-03-01 <br style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; ">

Reprints | Issue Contents

<br style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; "><br style="margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; ">Read more: Infographic: Epigenetics - A Primer - The Scientist - Magazine of the Life Sciences http://www.the-scientist.com/article/display/58007/#ixzz1FW6zBocT

This edition has a whole feature on epigenetics

http://www.the-scientist.com/2011/3/1/32/1/

 

http://www.the-scientist.com/2011/3/1/14/1/

 

http://www.the-scientist.com/2011/3/1/34/1/

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Hi All Epigeneticists,

 

Does anybody know a true transgenerational epigenetic study? I mean a study that observes epigenetic changes on F3 generation while only P0 is exposed. Besides vinclozolin study, is there any other like this? mouse or human? thank you!

 

google: epigenetics agouti

 

http://www.nature.com/ng/journal/v23/n3/full/ng1199_314.html

Rather' date=' our data show that it results from incomplete erasure of an epigenetic modification when a silenced Avy allele is passed through the female germ line, with consequent inheritance of the epigenetic modification. Because retrotransposons are abundant in mammalian genomes, this type of inheritance may be common. [/quote']

...and indels! google: epigenetics indels CNP [or CNV]

or: epigenetics indels "copy number" "novel architecture"

 

for instance: http://www.biotech.kth.se/courses/gru/courselist/BB2290/lectures/Bjursell_Lecture_4_HT10.pdf

...for a great overview and interesting tidbits (30 novel SNP's/person)... or:

http://sanford.duke.edu/research/papers/SAN10-03.pdf

http://www.cbra.org.br/pages/publicacoes/animalreproduction/issues/download/v7n3/pag103.pdf

 

I'm not finding a neat article about how extra copies of a gene will get moved (indels/transp...) and thus modified, regulated, and expressed differently, WHILE PRESERVING THE FUNCTION of the original copy. It seems to be a novel mechanism (to humans and a couple of other primate species) that is active only in specific regions of the chromosomes. Not surprisingly, considering how varied our diets have become over the past 10 thousand years, those more mutable regions are loaded with genes that affect the development of our digestive systems.

 

Interestingly, genes guiding digestive system development and structure are used later in gestation for contributing to the brain's development and architecture; so maybe that explains a lot about neuroses, sociopathy, civilization, creativity, and autism... when considering the evolutionary pressures of the past ten thousand years.

 

~ ;)

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  • 8 months later...

 

Nicotine Causes Epigenetic Changes in Mice that Spur Cocaine Addiction

 

http://blogs.discovermagazine.com/80beats/2011/11/05/nicotine-causes-epigenetic-changes-in-mice-that-spur-cocaine-addiction/

 

  • Looking deeper at the brain cells implicated in addiction and reward, they found that FosB, a gene whose expression helps cement addiction, was expressed at levels 74% higher than in mice who hadn’t had nicotine.
  • Investigating how nicotine could have this effect, they discovered that it was acting at an epigeneticlevel—in other words, changing the chemical packing of DNA. Here’s how:

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Interestingly, genes guiding digestive system development and structure are used later in gestation for contributing to the brain's development and architecture; so maybe that explains a lot about neuroses, sociopathy, civilization, creativity, and autism... when considering the evolutionary pressures of the past ten thousand years.

 

~ ;)

Yes most serotonin is produced and used by the gut (90%?) while the rest seems to be crucial to brain function and mood.

A point lost it seems on doctors now prescribing billions of antidepressant scripts ( serotonin re uptake inhibitors etc)

 

it is also intersting that the GUT /stomach can act independently of the brain. It fact it seems to be able to conter brain commands. the only bit of the body i know that can do this.

 

With all the bacterial communication going on in the GIT ( Quorum sensing), and its ability to harvest and create complex organic chemicals could the stomach be more intelligent that the brain?

 

 

 

 

 

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