Friday, January 3, 2014

Bilingual DNA


The University of Washington's Dr. John Stamatoyannopoulos has been a leader in the ENCODE Research, which is an extension of the Human Genome Project.  They continue to study human genes and DNA, the molecule on which the genes reside. The DNA contains coding and is copied in order that the proteins that do the work of our cells are produced.  But it takes a lot of inner cell regulation to get things just right.  Now that they know the genes, the researchers are trying to understand the regulation.  They are making surprising discoveries. 

From the University of Washington website: 
Scientists have discovered a second code hiding within DNA. This second code contains information that changes how scientists read the instructions contained in DNA and interpret mutations to make sense of health and disease.

It goes on to say:
Since the genetic code was deciphered in the 1960s, scientists have assumed that it was used exclusively to write information about proteins. UW scientists were stunned to discover that genomes use the genetic code to write two separate languages. One describes how proteins are made, and the other instructs the cell on how genes are controlled. One language is written on top of the other, which is why the second language remained hidden for so long.

DNA contains 4 different types of “bases” which are molecules that form a code (see first image, from genome.gov). Two bases form each "step" of the DNA "ladder." The groups of three bases, called “codons,” line up in precise order to give instruction to other mechanisms for the production of proteins.  We think of the codons as a language because their sequence affects the outcome beyond strictly chemical interactions.

The bases have an “end” for connecting to the side of the ladder and an “end” for producing the code. When DNA is copied, the middle splits open the long way and another molecule comes along to copy it.  This is done in the middle of the cell called the “nucleus.” Then the copy leaves the nucleus and is processed in the outer cell compartment to make the proteins. The protein production takes several intermediate steps, and the codon code is read to put together the protein.

DNA codes for proteins that carry on the functions of biological life.  Among these proteins are “transcription factors” (TF) that regulate gene production by binding to other parts of the DNA. The second picture is of gene regulation and the abstract for its article is here. You can see there are several elements involved in the regulation, both close and far from the gene (the black line is the DNA). There is often a feed-back system so that when the gene product is available, the chemical interactions lead to repression of further copying of the gene.  When the product decreases, the gene once again is activated. When the mechanism was first discovered, it seemed the transcription factors attached to DNA close to but a little bit apart from the actual gene.  It has been known for a few years that they can attach both to gene and non-gene areas and both near and far from the gene. But now the scientists have discovered an even more surprising situation.

The amazing part that was just announced is that the regulatory protein uses the same type of 3-base-per-codon language used in protein production. So, a protein can come back into the nucleus and combine with the DNA for a regulatory role using a set of 3 codon “letters” for a different function.

The paper is in Science, December 13, 2013.  It is limited access, so perhaps you can find it at a library, but it is written for those who understand the jargon.  Casey Luskin at ENV further explains aspects of it which you can read here.

Though much more research is needed, it will likely be necessary to understand the interplay of these molecules in order to cure certain diseases.  Over 85% of genes are already shown to have these regulatory codons, and the study has not covered all types of cells.

This discovery is BIG. The research shows that DNA has even more complexity than we imagined, and it greatly limits the possibility that all the functions of DNA simply came about from random molecular mutations. Because of the different language, current evaluations of natural selection are even less convincing than they were before. It shows the regulatory job of DNA is at least as precise as the production of proteins.  As researchers discover more activities for the genes, they find there are fewer changes the sequences can make without wrecking the whole system. That means even less chance for totally materialistic evolution.

To add a little related information from another paper, they have found that the genes themselves are involved in further activities.  Of special interest are the HOX genes which regulate organism development.  They have been found to interact with regulatory elements, and there may be “a largely unknown regulatory network relying on nucleotide sequence elements embedded within the ORFs [open reading frames] of most of these key developmental genes (Woltering and Duboule 2009)” from Lin et. al., “Locating protein-coding sequences under selection for additional, overlapping functions in 29 mammalian genomes”.  In other words, the genes read regulatory proteins  as well as producing the protein code when the individual is developing.

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