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.”  


Tuesday, December 22, 2015

Epigenetics: Under the Surface

What lies under the surface? The external and internal structure and function of the human body is complex and beautiful beyond belief. According to what master plan is the human body assembled? We could devote a lifetime of study even to scratch the surface of knowledge about molecular biology. Still, our knowledge of epigenetics is in its early stages.

A few decades ago basic knowledge of genomics—the science of structure, function, and mapping of DNA—was sufficient to satisfy most laypersons’ curiosity about heritable human characteristics. In recent decades our knowledge extends far beyond DNA with its code for protein production. In particular, we speak of the astonishing phenomenon of reproduction—the assembly of DNA-produced protein substances during prenatal body development. Genomics reveals but a small portion of the complex story of reproduction of a unique new life. Epigenetics is the new buzz-word. 

At the risk of trivializing a majestic biological process with a mundane analogy, we illustrate with a culinary example. When a chef prepares a gourmet dish, all prescribed ingredients must be initially assembled. More important is the activity to follow: (1) adherence to a coherent recipe (2) use of correct utensils (3) appropriate procedure (4) proper control of necessary factors such as temperature, and (5) maintaining favorable conditions when the project is complete. We see that in addition to the initial assembly of appropriate ingredients, far more is involved in a successful gourmet production.

We transition to prenatal production of a new life—admittedly a giant leap. One important term is “gene expression.” Acquiring the biological components of the human body proteins is the initial step. But fabrication of the components is ultimately more important. The latter is a topic under the heading of epigenomics. How does the assembly process unfold? Life scientists define gene expression as the process by which information from a gene is used in the synthesis of a functional gene product. Production of a complex, unique new human life in the womb is a creative process far beyond our imagination. Gene regulation insures that genes function to produce specific cells at the proper time.

Let us consider a few molecular wonders of the reproductive process. We quote from opening statements of a lengthy Quiagen website. “It is known these non-genetic alterations are tightly regulated by two major epigenetic modifications: chemical modifications to the cytosine residues of DNA (DNA methylation) and histone proteins associated with DNA (histone modifications.)” The Quiagen site continues, “Epigenetics is one of the fastest-growing areas of science and has now become a central issue in biological studies of development and disease.”

For the remaining space in this post we discuss methylation. DNA methylation describes the addition of a methyl group containing one carbon and three hydrogen atoms. This molecule attaches to one of the nucleotides of the DNA molecule—namely, cytosine. In our previous references to the base pairs in DNA which code for proteins, CG is one of the “alphabetic letters” of the DNA protein coding scheme, along with AT. C abbreviates cytosine. The methylation of DNA may occur owing to environmental conditions. Or, it may occur as a result of naturally occurring cell processes. Whatever the cause of methylation, it may result in developmental advantages during the process of body formation during reproduction. Methylation is a disadvantage if it results in a disease state. The methylation process is heritable, even if it results from environmental factors.

Methylation of DNA is important during the many stages of fetal development in which some processes are turned on while other processes are turned off. These findings are important as they provide insight into regulatory elements guiding tissue specification that lead eventually to organ functionality.

Bioscientists are working to unlock more secrets of epigenetics. We believe that in our lifetime many more wonderful truths concerning knowledge of life processes, physical wellness, and healing will be discovered. Of the hundreds of written sources dealing with epigenetics, many state that the processes arising during fetal development are still largely unknown. 

Many personal questions concerning wonders of life are hidden with the Creator of all things. King David celebrates the omniscience of God in his majestic Psalm 139:13-16:

For you created my inmost being: you knit me together in my mother’s womb. I praise you because I am fearfully and wonderfully made; your works are wonderful, I know that full well. My frame was not hidden from you when I was made in the secret place. When I was woven together in the depths of the earth, your eyes saw my unformed body. All the days ordained for me were written in your book before one of them came to be.      


Tuesday, December 15, 2015

Epigenetic Prologue

We have experienced a reprise of the fascination triggered when a new life enters the family. At the risk of being repetitive, we must acknowledge renewed awe of the traits and skills manifest by very young children long before the age of six months. Our visits to church, the supermarket, and other public venues supply ample observational opportunities. In the earliest months of her life we recently observed our friends’ daughter beaming exuberantly at us across the aisle during Sunday morning hymn time. On another personal level our new grandson, two months old, has been smiling and vocalizing enthusiastically for several weeks.

You may ask how epigenetics affects our knowledge of early development of human consciousness, the subject of our opening paragraph. Backing up just a few months before these children were born, one could also inquire how epigenetics relates to the marvelous sequential prenatal development of each living human. We increasingly hear medical advice on healthy lifestyles, disease prevention, and new treatments for personal health crises. Medical technology is increasingly the application of epigenetic knowledge. 

Epigenetics has entered our modern vocabulary to supplement our more traditional knowledge of genetics. (“Epi-” connotes above, beyond, or in addition to when used as a prefix.) For example, the basic physical structure, health, and function of the body may be studied under the topic of epigenetics. Therefore, we have a progression of studies—the genome, the proteome, and the epigenome. We project that our knowledge of the epigenomics is only at its beginning. What is in store for proliferation of our knowledge and enhancement of our quality of life in future decades?

Stories and examples enhance our ability to learn new concepts. After building a new home we inspect the empty dwelling to determine its initial structural integrity. We establish that the home’s blueprint was carefully followed. In the following months the home will acquire unique qualities as it is progressively finished and furnished with enhancements such as trim, color of paint, and wall decorations. These enhancement “add-ons” are not provided by the blueprint.

Application of knowledge of epigenetics, likewise, does not alter our respect for the genetic role of the DNA code. To a large degree, environment and known gene expression mechanisms are capable of effecting significant changes in human health. These are examples of epigenetics, a broadened area of inquiry we will progressively discover in coming years.

In personal continued study of epigenomics, we are often deluged with bioscientists’ relentless efforts to connect this new knowledge with an affirmation of undirected naturalistic evolution. We look forward to discussing some of the molecular basis of epigenetic processes in future posts. As we discover more astonishing design and functional features of living things and their capabilities to adapt and reproduce, the case for evolution weakens as the case for past and present acts of the Creator becomes stronger. Our God is the author of the genome, the proteome, and the epigenome!


Wednesday, December 9, 2015

Epigenetics and Phenotype

Epigenetics is a new and unfamiliar term to many non-scientists. The term signifies inherited changes to the phenotype (physical and behavioral traits) that are not caused by the genetic code of DNA. To bioscientists knowledge of epigenetics opens new medical knowledge to enhance human health and longevity. It is the next step in the lexical sequence—genomics, proteomics, and epigenetics. 

Most laypersons are familiar with the term genomics. They know that most physical traits result from DNA inheritance. Knowledge of another field, proteomics, has spun off from genomics. The human DNA code is responsible for building physical traits by  its ability to produce proteins, the building blocks of our physical bodies. Proteomics is a specialized knowledge of the composition, structure, and multiple functional roles of proteins.

We focus on two other related terms which have become part of our biological lexicon: genotype and phenotype. Our genotype is our personal genetic sequence of heritable genes making up our DNA. It provides the code for the manufacture of multiple proteins which compose our physical body. It is not dependent on any environmental factors. Personal genotypes are intrinsic to one individual.

A phenotype, in contrast, is observed as outward, physical traits. It could be influenced by environmental factors other than our DNA sequence. Unique traits and personal behavior are also considered part of our phenotype. We may see that phenotypes are dependent on genotypes to a large degree. For example, physical size and other traits such as hair and eye color trace to our genotype.

Explanation of the human architectural body plan is not simply a matter of understanding the function of DNA in inheritance. This basis of inheritance is exceedingly important, but with the passage of time we have become aware of the wonder and complexity of other factors—epigenetic factors which govern the engineering of body plans. We introduce another term in our biological lexicon. It is termed developmental biology. Epigenetics may be linked with developmental biology to create developmental epigenetics.

We introduce new vocabulary to help us focus on the cutting edge in developmental biology. Several new expressions may trigger expanded reader interest in this field: gene expression, gene regulation, cellular differentiation, and morphogenesis. All terms hold the potential for future post topics.

Our family has become aware once more of the miracle of developmental biology in a short nine months. A new grandson has joined his two-year-old brother and four-year old sister in another manifestation of the developmental wonders of the creation of a new life in less than one year. Our family has termed the event a “divine developmental miracle.”

The arrival of a new grandson inspired your blogger to create a series of posts on our family version of “developmental biology” in 2013. I link one of many posts from that sequence. You may also click on the previous four posts (older post) or the seven posts to follow (newer post).


Friday, December 4, 2015

More Protein Wonders

Proteins begin their lives as chains of amino acids in the body. In humans, protein-forming amino acids are either acquired in foods we eat (essential amino acids) or are manufactured in our body (non-essential amino acids). Essential and non-essential amino acids are coded by the DNA molecule to produce the proteins of the body. Twenty different protein-forming amino acids are chained together in myriad  ways according to instructions in the oft-cited DNA code. The human body operates with many thousands of different proteins.

The term DNA code is a powerfully meaning-laden term. When we were young some of our entertainments were games of code-cracking or secret code-breaking. In every case the code was devised by another person, an indicator of intelligence of the deviser of the code. They also affirm our own ability as intelligent code breakers. In the DNA code we observe that when we recognize the identity of the code author, our own sense of perception and comprehension is affirmed.

Are there limits to the number of proteins possible? Bioscientists speculate that there are as many as ten million different proteins among all living things on earth, while humans have upwards of 50,000. Proteins begin as chains of amino acids termed polymers. We highlight a fascinating capability of proteins: their ability to fold into three dimensional shapes. The three dimensional shape relates to the function of that particular protein in keeping with the biological principle of “form fits function.” In theory, there are no limits to the number of possible proteins. 

The unique three dimensional conformation of each protein, according to scientists, is dictated by the original amino acid sequence. Scientists also attribute the three dimensional structure to the mediation of other protein cells, assisted by molecular “chaperones.” These explanations point to a possible cause, but not an entirely satisfying explanation of how the cause works to accomplish the observed effect. Herein is a mystery. The line between a naturalistic cause and effect, such as the forces we exert to accomplish minor repairs of an inoperative device in our home, and a complex phenomenon such as protein folding, is not always sharply defined.

In early science lessons we learned that “proteins are the body’s building blocks,” rather like bricks and lumber incorporated into a new home. The three-dimensional conformation of complex protein molecules may help us envision the idea of “building blocks.” While this characterization of proteins is accurate, the story is incomplete. Three-dimensional protein molecules have many functions in the human body. The functions include enzyme catalysis of metabolic reactions, immune responses, cell signaling, and information processing. Each previous term could be the subject of lifetime study by specialists in bioscience. 

Where does a divine miracle end and a natural process begin as we study the astounding complexity of life—in particular, human life? We may easily perceive physical life forms and life processes as intelligently designed. We may also go further to say that human life forms are the product of a divine, transcendent miracle. As we contemplate the existing complexity of physical body structure and the functions operating to make its systems work, we are struck with wonder. God is the author of both primary causes and secondary causes. Primary causes are transcendent miracles of creation such as the beginning of our universe and the immediate creation of human life forms. Secondary causes are moment to moment transformational or sustaining miracles such as the miracles of our working bodies.