2017/06/30

The entire concept of “gene” has to be reconsidered

New discoveries change our understanding of genes and their purposes

http://jonlieffmd.com/blog/new-complexity-in-dna-regulation

Highlights:

"But, now multiple vast networks of regulation have been found that include more than forty different types of tags placed on both DNA and the protective histone proteins that allow access to DNA strands. All of these tags alter genetic function and are based on the actions of protein enzymes."

Another type of regulation involves the shape of the DNA both in small loops and large placement inside of highly structured nucleus scaffolds with dramatic influence on genetic functions.

The very complex editing of messenger RNA can make up to 500 different proteins from a single strand of DNA—what used to be called a gene, but now is hard to define. Genes can overlap and triggers of regulation can happen in the gene or in the regulatory strand.

What is equally amazing is that mental events—thought—almost instantly triggers large networks of many genes at the same time. How does this happen?
  

Now entirely new sets of factors have appeared that are based on physical properties of the coding of RNA and the liquid phase transitions that separate active and inactive sections of the chromosomes. The first unusual new physical properties occur when there are repeated patterns of code. The regions of regulatory code where there are large amounts of repeats have been correlated with multiple different degenerative diseases such as Huntington’s and ALS. The second is the way that active and inactive sections of the DNA are in different regions of the nucleus.

It is not known how many overlapping layers of regulation there are:

Some include:

  • Histones protect DNA and must be opened to be used. There are now forty different tags that determine whether histones can be opened or not to utilize DNA.
  • There are many newly discovered tags on DNA itself that alter function.
  • Thousands of proteins called promoters and enhancers start and stop DNA function.
  • Promoters work in many different places for each gene and in different places for each type of human cell. Also, for even more complexity, multiple promoters combine into larger machines, some touching the DNA and some only combining with the other promoters. Multiple structures exist for each gene in different places.
  • There are multiple different places where transcription starts for each “gene”, again undermining the notion of the simple “gene.”
  • Thousands of large and small RNAs interact in multiple ways to regulate what pieces of DNA are used.
  • Many different mechanisms are used to repair DNA errors without obvious direction.
  • Eight million factors affect the RNA particles that are made from at least 20% of all DNA (maybe up to 50%). Messenger RNA somehow determines multiple different edits from the same pieces of DNA.
  • Pieces of DNA and RNA are taken from multiple places, strands are cut out and others sewn together without clear direction.
  • In some DNA there are two superimposed codes at once in one section of DNA. These are related to new messenger RNA folding, and multi-use codons called “duons.” The first purpose is to transcribe DNA code to RNA code to make proteins. The second purpose is to bind regulatory factors, as the regulatory regions do to trigger other genes.
  • Transcription factors bind inside at least 13% of “genes” themselves, not just the regulatory regions nearby. This finding was truly shocking since the DNA in the gene, then, must code for two meanings at once for two entirely different purposes.
  • RNA splicing, can make up to 500 different proteins from the same pieces of DNA. The RNA cuts out sections and sews others together. Recently, it has been demonstrated that the pieces that are sewn together by the messenger RNA may come from multiple different areas that used to be called individual genes.
  • Four million different switches are active, often operating in multiple places at once; 18,000 places where active RNA is made; and 8 million different particles interacting to regulate these RNAs.
  • The entire concept of “gene” has to be reconsidered because messenger RNA takes pieces from different regions to make one RNA edit for a protein.
  • The 3D shape of the DNA chromosome is correlated with the activity of the genes inside.
    • The links exist at multiple levels.
    • Loops of chromatin make space for enhancers to land. A larger relationship exists for specific places in the nucleus to impact on particular active DNA sites.
    • Special protein structures alter polymerase activity.
    • Chromosomes with fewer active genes are placed at the edge of the nucleus while the active ones are near the center.
    • Less active sections are placed near the nuclear lamina, which is close to membrane.
    • The location can suppress the genetic machinery.
    • If the chromatin is opened but not used, the entire section is moved to a different location.
    • The exact location of the gene in space in the nucleus influences its activity.
    • To fit 2 yards of DNA into a tiny nucleus is a monumental engineering feat. DNA is highly compacted yet has to be instantly available to rapidly make proteins in neurons with a momentary change of thought."
My comment: Messenger RNA takes pieces of genes from different locations to make one RNA edit for a required protein. Where is the regulation for this? Certainly not in gene sequences. These epigenetic mechanisms, 3D genome, overlapping genes and codon duons tell us about an extremely complex language that points to perfect design. There is no such a thing as mutation driven evolution. Gene centric population genetics and the theory of evolution have seriously failed. Again.

Life is not driven by gene sequences. Genes are driven by lifestyle. Don't get lost.