Wednesday, December 30, 2015

Chemical Tags for Our Genome

DNA contains our genetic inheritance. In the DNA molecule there exists a code for the assembly of all the proteins in our body—up to 50,000 proteins. In this way, DNA is the reference manual for the materials of which our body is composed. These chemical materials must be assembled properly or they will not become a living, properly formed, functioning human being. A multitude of additional chemical compounds tell the proteins what to do in order to achieve their proper function and formation. These additional chemical compounds comprise the epigenome, a necessary chemical supplement to the genome of DNA. It may be considered a second layer of information necessary to form a coherent living human (or any other living creature).

DNA in our bodies is wrapped in chemical “tags.” In previous posts we have mentioned  two primary tags: DNA methylation and histone modification. For this post, we deal with the second chemical “tag:” histone modification. The DNA in each human cell remains fixed for life. Chemical “tags” called histones, collections of protein molecules, influence the DNA molecule. These “tags” affect inactive genes, making them unreadable. At other times, the chemical “tags” make genes accessible and readable. Different genes are active in different types of cells at different times. My personal fascination with epigenetics currently relates to prenatal development, but epigenetic tags operate throughout our lifetime.

The NHGRI (National Human Genome Research Institute), an arm of the NIH (National Institute of Health) publishes many fact sheets, including topics on epigenetics. We quote several statements to help us understand a small part of the complexity and wonder of the human body: “…DNA in cells is wrapped around histone proteins, which form spool-like structures that enable DNA’s very long molecules to be wound up neatly inside the cell nucleus. Histone proteins attach a variety of chemical tags to DNA. Other proteins in cells detect these tags and determine whether that region of DNA should be used or ignored in that cell.”

A YouTube graphic from GSLC (Genetic Science Learning Center) illustrates what happens to the histones called “octamers.” DNA sometimes tightly wraps around these histones like “beads on a string,” making inactive genes unreadable. At other times DNA loosely wraps the histones, making active genes easily accessible.

One pillar of evolution traditionally cited by scientists has been the presence of “junk DNA” in non-protein-coding sequences. Only a small percentage of human DNA codes for proteins. The function of non-coding DNA until recently has been dubbed “junk” because it was assumed it was left over from earlier eons but no longer served any purpose. Recently the NHGRI, cited above, sponsored the ENCODE project. In the last decade, ENCODE scientists have discovered that 80% of non-coding DNA has regulatory function within the cell. Eric D. Green, Ph.D., director of the NHGRI branch of NIH says “…most of the human genome is involved in the complex molecular choreography required for converting genetic information into living cells and organisms.”

The regulatory function of this vast wealth of non-coding DNA, rather than useless “junk,” is now recognized as an epigenetic layer to enable gene expression and regulation and aid in the startling phenomenon of embryonic stem cell differentiation. Stem cells are pluripotent; they are able to differentiate into all of the 220 different cell types needed to construct the many tissues necessary to form all body organs and eventually, the integrated systems of the human body.

When we examine a newborn human baby, we notice the complexity of morphology of each baby part. Does he have all his fingers and toes? Does she look like her mother or her father? Are the dozens of internal organs present and functioning as they should? Our answers indicate but a minuscule understanding of the marvelous complexity of genetic inheritance. The more we understand, the closer we come to grasping the significance of Psalm 139:14 (NIV): I praise you, because I am fearfully and wonderfully made; your works are wonderful; I know that full well.”