Epigenetics and Cancer

[The Curious Squid]

It didn't bore me at all, it just stopped me dead in my tracks because I couldn't understand it.

I think that the subject would be amazingly interesting to me if I could follow it

[FedUpWithFaith]

The only issue is that people often see this as "acquired characteristic", or Lamarckism as it is best known, because it is not directly encoded in the DNA. The epigenetic marks themselves are however influenced by the environment, but so is the rate of mutation, so the argument for Lamarckism is fallacious.

I'm not sure it's fallacious to say this is a form of Lamarckian evolution. The fact that mutation and other processes are involved doesn't seem to detract from that unless there is a counterbalancing mechansim, which I don't see.

The fascinating thing about epigenetics is precisely how the environment can induce acquired inherited traits from one generation to the next without relying totally on much slower mutation or recombination pathways. Moreover, that environment isn't just the outside world but the internal world engendered by culture and lifestyle. The way populations choose to live their lives affects the heritable fitness of the next generation.

[charlou]

Seriously. I'm fascinated.

[MedGen]

The only issue is that people often see this as "acquired characteristic", or Lamarckism as it is best known, because it is not directly encoded in the DNA. The epigenetic marks themselves are however influenced by the environment, but so is the rate of mutation, so the argument for Lamarckism is fallacious.

I'm not sure it's fallacious to say this is a form of Lamarckian evolution. The fact that mutation and other processes are involved doesn't seem to detract from that unless there is a counterbalancing mechansim, which I don't see.

The fascinating thing about epigenetics is precisely how the environment can induce acquired inherited traits from one generation to the next without relying totally on much slower mutation or recombination pathways. Moreover, that environment isn't just the outside world but the internal world engendered by culture and lifestyle. The way populations choose to live their lives affects the heritable fitness of the next generation.

In the scientific domain epigenetic modifications classically mean anything inherited outside of DNA. Generally now they tend to be attached to specific chemical modifications that occur on cytosine nucleotides (5meC) as well as additions to the amino acid building blocks of the proteins that make up the majority of chromosomes (interestingly it was originally thought that proteins were the heritable material that Mendel described as factors because there is so much of the bloody stuff in our chromosomes). How these modifications translate to the phenotypic level is not fully understood yet, though there are a few examples in genetic disease that involve disregulation of specific (and consistent) epigenetic modifications, or genomic imprints. These imprints occur between two loci, sometimes the same gene on sister chromatid, sometimes two different genes, whereby they are differentially silenced by epigenetic modification in a parental inheritance-dependent manner. One of the most commonly cited is that of the oppositely imprinted genes IGF2 and H19. One is maternally inherited, the other paternally, though the actual genes are still present, they are selectively silenced by specific chemical modification to regions around the gene (these are called CpG islands), as well as to the associated chromatin histones (the protein that DNA is wrapped around to make chromosomes).

The reason that Lamarckism doesn't hold water, in this case particularly, is that is specifically stated that "acquired characteristics" were the mechanism of organisms changing transgenerationally. That would require a consistent mechanism over an evolutionary timescale, which it doesn't. As far as is currently known transgenerational epigenetic modifications are highly labile and transient, hence "acquired characteristics" stays in the bin were it belongs.

It is also worth pointing out that the epigenetic marks that are consitently inherited are for specific reasons, such as gene dosage compensation and other genomic imprints as mentioned above e.g. X chromosome inactivation; in females one X chromosome is randomly "inactivated" by large swathes of epigenetic modifications and other mechanisms to compensate for the fact that males only have one X chromosome. Two active chromosomes could be potentially deleterious, and in fact this is the case in XXX 47 females who display varying levels of learning difficulties, most likely due to large gene dosage effects from the additional X chromosome.

With respect to the last part that I've bolded; that in itself is not epigenetic, rather it creates differing selection pressures between cultures, that had human populations remained isolated, could have translated into sufficient barriers to reproduction as to lead to speciation, but they didn't because, as is always the case, humans are too fucking randy and they wanted to fuck all the ladies in all the neighbouring villages, resulting in continued gene exchange, and preventing the formation of significant reproductive barriers.

[GenesForLife]

So, MasterBaker, you look like a biologist :-)

I'm also one of those and am particularly keen on Cancer research, I wonder if blocking all expression of methylases in cancer cells would lead to the expression of apoptotic genes / p53 (the methylation of which is a distinctive hallmark of cancer, if the gene for p53 is not already mutated) and hence induce cell death, I'd trust the blocking methodology to be Morpholino antisense, preferably.

[GenesForLife]

The only issue is that people often see this as "acquired characteristic", or Lamarckism as it is best known, because it is not directly encoded in the DNA. The epigenetic marks themselves are however influenced by the environment, but so is the rate of mutation, so the argument for Lamarckism is fallacious.

I'm not sure it's fallacious to say this is a form of Lamarckian evolution. The fact that mutation and other processes are involved doesn't seem to detract from that unless there is a counterbalancing mechansim, which I don't see.

The fascinating thing about epigenetics is precisely how the environment can induce acquired inherited traits from one generation to the next without relying totally on much slower mutation or recombination pathways. Moreover, that environment isn't just the outside world but the internal world engendered by culture and lifestyle. The way populations choose to live their lives affects the heritable fitness of the next generation.

Not sure you can say that, mate , only epigenetic modification in the Germ Cell line can be heritable...

[Psi Wavefunction]

The only issue is that people often see this as "acquired characteristic", or Lamarckism as it is best known, because it is not directly encoded in the DNA. The epigenetic marks themselves are however influenced by the environment, but so is the rate of mutation, so the argument for Lamarckism is fallacious.

I'm not sure it's fallacious to say this is a form of Lamarckian evolution. The fact that mutation and other processes are involved doesn't seem to detract from that unless there is a counterbalancing mechansim, which I don't see.

The fascinating thing about epigenetics is precisely how the environment can induce acquired inherited traits from one generation to the next without relying totally on much slower mutation or recombination pathways. Moreover, that environment isn't just the outside world but the internal world engendered by culture and lifestyle. The way populations choose to live their lives affects the heritable fitness of the next generation.

Not sure you can say that, mate , only epigenetic modification in the Germ Cell line can be heritable...

Yeah but the vast majority of life is unicellular...

You should check out cytotaxis/cortical inheritance in Paramecium! (Eg. Beisson & Sonneborn 1965 PNAS) Fascinating stuff...

[GenesForLife]

The only issue is that people often see this as "acquired characteristic", or Lamarckism as it is best known, because it is not directly encoded in the DNA. The epigenetic marks themselves are however influenced by the environment, but so is the rate of mutation, so the argument for Lamarckism is fallacious.

I'm not sure it's fallacious to say this is a form of Lamarckian evolution. The fact that mutation and other processes are involved doesn't seem to detract from that unless there is a counterbalancing mechansim, which I don't see.

The fascinating thing about epigenetics is precisely how the environment can induce acquired inherited traits from one generation to the next without relying totally on much slower mutation or recombination pathways. Moreover, that environment isn't just the outside world but the internal world engendered by culture and lifestyle. The way populations choose to live their lives affects the heritable fitness of the next generation.

Not sure you can say that, mate , only epigenetic modification in the Germ Cell line can be heritable...

Yeah but the vast majority of life is unicellular...

You should check out cytotaxis/cortical inheritance in Paramecium! (Eg. Beisson & Sonneborn 1965 PNAS) Fascinating stuff...

Unicellular organisms cannot, in theory, develop cancer though, can they?

[GenesForLife]

So, MasterBaker, I've just started to work with bioinformatics databases (nothing more than a hobby, mind) and I wanted to ask if you have any idea about sequence retrieval tools for possible miRNA transcript identification. Coming back to cancer characterisation, apparently 217 miRNAs can characterise cancer better than 16,000 mRNA transcripts