An End to Endless Forms: Epistasis, Phenotype Distribution Bias, and Nonuniform Evolution

"An important implication of these studies is that diversity is largely the outcome of the evolution of gene regulation rather than the emergence of new, structural genes."

This corroborates evidence from the latest evolutionary studies that the switching on and off of silent non-coding regulatory parts of the DNA are responsible for the development of unique evolutionary traits. Perhaps, this is why the non-coding introns form a massive 98%-99% of the genomes of all living organisms as compared to the minor 1-2% coding exons.

Additionally, this also points to the fact that the field of epigenetics is not really all that surprising. I think "epigenetics" might be a misnomer. All the apparently post-transcriptional modifications are not really controlled in an autonomous fashion but by regulatory non-coding fragments on the DNA. "Epigenetics" is the gene-expression of the introns. While exonic genes transcribe proteins, intronic genes (formerly known as "junk" DNA) transcribe "epigenetic" instructions.

Thus methylation, chromatin packaging and all the other "epigenetic" phenomena might be merely reflections of an evolutionary adaptation to environmental stimuli - conferring distinct advantages to survival. Can cancers modify and regulate the non-coding segments of the DNA to manipulate "epigenetics" to their own benefit? I would be interested in hearing what you think about this.

My understanding begins with the term of 'diversity'. To me, diversity points to differences on the basis of homogeneity formed within a relative short time. Gene regulation takes a much faster response to environmental challenges than any DNA sequence mutation and novel genesis, and therefore may be preferred by changes needed in a short time. As you said, a large proportion of the gene regulation plasticity may hide within the so-called intronic regions, at least in the forms of micro RNA, although I also believe the extremely redundant inter-gene regions could also have other fundamental effects other then gene regulation, e.g., protection from damage to error-sensitive exons by immersing them into relatively error-tolerant mass.

But epigenetic is not all about post-transcriptional modifications. For example, promoter CpG island hypermethylation suppressed gene transcription and thus should not be considered as post-transcription. Plus I am not aware of any study showing methylation or histone modifications is controlled or pre-programmed by certain intronic regions. They are for sure another dimensions of gene regulation but still we are not clear about how they are coded or inherited.

Another thing for sure is that epigenetic changes are more dynamic than DNA mutation. Thus for a particular tumor, if we think of individual tumor as a process of micro-evolution but obviously much faster, faster gene regulations by epigenetic changes would be an easier way to go through, and epigenetic-mediated gene regulation is more susceptible to environmental changes, and thus epigenetic changes may be relevant to carcinogenesis caused by environmental factors.

"An important implication of these studies is that diversity is largely the outcome of the evolution of gene regulation rather than the emergence of new, structural genes."

This corroborates evidence from the latest evolutionary studies that the switching on and off of silent non-coding regulatory parts of the DNA are responsible for the development of unique evolutionary traits. Perhaps, this is why the non-coding introns form a massive 98%-99% of the genomes of all living organisms as compared to the minor 1-2% coding exons.

Additionally, this also points to the fact that the field of epigenetics is not really all that surprising. I think "epigenetics" might be a misnomer. All the apparently post-transcriptional modifications are not really controlled in an autonomous fashion but by regulatory non-coding fragments on the DNA. "Epigenetics" is the gene-expression of the introns. While exonic genes transcribe proteins, intronic genes (formerly known as "junk" DNA) transcribe "epigenetic" instructions.

Thus methylation, chromatin packaging and all the other "epigenetic" phenomena might be merely reflections of an evolutionary adaptation to environmental stimuli - conferring distinct advantages to survival. Can cancers modify and regulate the non-coding segments of the DNA to manipulate "epigenetics" to their own benefit? I would be interested in hearing what you think about this.