Sunday, April 28, 2013

Nessa Carey, The Epigenetics Revolution (2012)

A recurring theme running through the posts on this blog is the recognition  of a unit of information as the fundamental units of physical nature.  Collateral to this theme: the transmission of information and the avoidance of errors in translation during transmission, whether those communications are at the cellular level or communications among species or between individuals of a species.  (See March 6, 2012, August 15, 2011, November 27, 2010August 23, 2009, and August 17, 2009 posts).  A slight change in a unit of information can potentially change the "meaning" of a larger assembly of units of information, things akin to what we might label words, a sentence, a paragraph, an entire story.  Matthew Ridley uses this kind of analogy when he discusses the genome.  (See November 27, 2010 post):

"Ridley calls the genome a book, the chromosome a chapter, the gene a story, an exon a paragraph, a codon a word consisting of three letters, and a base is a letter, either (in the case of DNA) an A, C, G, or T (or U in the case of RNA), for adenine, cytosine, guanine, and thymine, each consisting of one or two aromatic rings and arrangements of carbon, hydrogen, nitrogen, and/or oxygen atoms. These chemical units are the basic units of information that comprise life forms, but alone they do not give rise to life. What gives rise to life is (1) the pairing of these letters along a double helix that makes up DNA, and (2) their subsequent transcription into RNA to form three letter codons, which, (3) are subsequently "translated" into a specific amino acid depending on which three of the four letters are transcribed and their sequence. (4) The particular chain of amino acids creates a protein. By this process, it is said that "genes" code for "proteins." While the RNA amino acid chains may have been the earliest form of life, "life" as we know it received a boost with the creation of cellular membranes to form the first cells that carried the proteins containing genetic information central for the cell's organization. This development is still not fully understood.

"This ability of the genes to copy themselves, read and transmit their story, under the right conditions, is the ability to create another life form. . . . [T]hese units of information [have the ability] to communicate among themselves --- an electrochemical means --- to say "Let's stick together," or "Let's avoid each other," and then to store itself as if in memory. This is what we find in the genome, whatever the species."

"Life began with RNA --- which by itself can replicate itself, and translate and transmit its meaning, as well as catalyze with --- break up or join with --- other chemicals, creating amino acids and proteins. The storage device for these words and paragraphs is DNA. An RNA gene found on chromosome 1 translates the information found in DNA to proteins, which become the primary agent for carrying out the direction specified by the information contained in the genes within a cell." 

A prior post discusses how alterations in the structure of DNA and the chromosome, what we typically refer to as mutations, can lead to changes in species.  (See December 14, 2010 post):

"And there are a variety of mutations of the genetic code. The most common is the equivalent of a typographical error in the process of copying the genetic code --- a substitution of one of the four letters for another. But there are also mutations involving deletions of code and insertions of repeating code or duplications. Sometimes these mutations actually mean something --- changing something about the phenotype in which the genetic code resides, but many, many times these changes mean nothing --- they don't change a thing about how the gene works. Some genes simply lose their meaning over time because they are no longer used, and these are called fossil genes. And some mutations that do have meaning simply do not survive to live another generation because selection is neither accommodating nor forgiving. When mutations occur repeatedly and have meaning --- in the sense that it changes something about the phenotype in which it resides --- and selection favors the survival of that mutation, then given enough time (many generations, thousands of years) we can find new species evolving. Carroll has reduced his mantra of chance, selection and time to this expression: "i) given sufficient time, ii) identical or equivalent mutations will arise repeatedly by chance, and iii) their fate (preservation or elimination) will be determined by the conditions of selection upon the traits they affect."

Epigenetics concerns a molecular examination of genetics, and how substitutions of molecules on a piece of DNA can have consequences for the phenotype of which the DNA is a part.  This does not involve a change in the arrangement of the genetic letters, or the words, or the paragraph or the chapter, in Ridley's terms.  These molecular alterations change the way in which genes are expressed.  Broadly speaking, the "environment" is believed to play a role in these alterations, importantly during embryonic development, but at any stage of life.  And recent research is beginning to show that epigenetic changes can be inherited for a generation or more. The change in gene expression can alter the very nature of cells themselves. 

Currently, there are two fairly well known types of epigenetic modification.  The first is called DNA methylation, which involves the addition of a methyl group (carbon atom bonded to 3 hydrogen atoms) to one of Ridley's genetic "letters" --- cytosine.  The underlying DNA sequence is not altered by the modification.  Cytosine, says Nessa Carey in The Epigenetic Revolution, has been "decorated," not changed.  DNA methylation is associated with genes that are turned "off."  This can lead to a number of disorders that the individual suffers from for the rest of their life.  In addition to turning a gene off, it is also known to prevent messenger RNA molecules from being produced, thus stopping the DNA transcription machinery from working.  The second epigenetic modification is called histone acetylation.  Histone acetylation is associated with turning genes on, although that is not always the case.  Again the underlying gene sequence is not altered.

Understanding epigenetic modifications allows us to better understand why "identical" twins are not identical. It leads to a better understanding of certain disorders (cancer, obesity, and other disorders).  Nessa Carey describes a wide number of research projects in which science is studying whether epigenetic modifications triggers a particular disorder.  I will only discuss one: early childhood abuse triggers an event that has consequences into adulthood; childhood trauma causes an alteration in gene expression in the brain that is generated or maintained by epigenetic mechanisms.  The focus of this research is on a hormone known as cortisol, which is produced in response to stress.  Research shows that the average level of cortisone production in adults seems to be higher for persons with traumatic childhoods.  The hippocampus in the brain responds to stress, and it releases two hormones:  corticotrophine-releasing hormone and arginine vasopressin.  They stimulate the pituitary, which in turn releases a hormone called adrenocorticotrophin into the bloodstream.  When cells of the adrenal gland take up adrenocorticotrophin, the cells release cortisol.  Some of this cortisol makes its way through the bloodstream back to the brain.  Receptors in the hippocampus, hypothalamus and pituitary all "recognize" cortisol and the cortisol binds to these receptors creating a signal to the brain to calm down.  This reduces the production of cortisol and the result is that we are prevented from being overstressed.  Adults who suffered traumatic childhoods are actually overstressed and produce too much cortisol.  Something about the feedback loop that would normally reduce stress is broken.  Research on mice suggests that DNA methylation of the arginine vasopressin hormone leads to increased expression of this hormone and the stimulation of a stress response.  This is all very contentious at this time, and more research is underway on the impact of stress, and other brain-related topics such as memory.

Carey reports on research involving honeybees.  The research is far from conclusive, but there is interest in histone modifications in the control of honeybee development and activity and DNA methylation in the changes of honeybee memory. Carey describes research showing that expression of different epigenetic enzymes varies between different social groups in colonies of ants, and the data suggests that epigenetic control of colony members may be the mechanism that has evolved in the social insects.

In The Social Conquest of Earth, biologist E.O. Wilson referred to epigenetics in an entirely different way.  (September 12, 2012 post)  To determine what evolved that made us humans, he begins by asking "What is human nature?" He suggests that the place to look for the answer to this question is "in the rules of development prescribed by genes, through which the universals of culture are created." Human nature, he says, is the "inherited regularities of mental development common to our species. They are epigenetic rules, which evolved by the interaction of genetic and cultural evolution that occurred over a long period in deep prehistory. These rules are the genetic biases in the way our senses perceive the world, the symbolic coding by which we represent the world, the options we automatically open to ourselves, and the responses we find easiest and most rewarding to make. . . They determine the individuals we as a rule find sexually most attractive. They lead us differentially to acquire fears and phobias concerning dangers in the environment, as from snakes and heights, to communicate with certain facial expressions and forms of body language, to bond with infants; to bond conjugally; and so on across the wide range of other categories of behavior and thought." (See September 17, 2012 post).  Wilson's use of the term epigenetics is more related to the term epigenesis, and this is slightly (although not entirely) different than the study of epigenetics that forms the basis of Nessa Carey's The Epigenetics RevolutionNor is Wilson approaching this subject from a singularly genetic angle.  He is concerned with the interaction of genes and culture (broadly considered) in the evolution of a social unit.   I suspect at the bottom of Wilson's use of the term are the neurochemical actions behind learning and memory that triggers epigenetic change affecting the neurological system resulting in  patterns of behavior.  Of interest to Wilson would be social behavior; for example, why do primates groom each other?

Epigenetics as described by Nessa Carey or in the sense intended by Edward Wilson both involve the transmission of information, alterations in the information units transferred, and the effect of these information transfers (positive, negative or neutral). This area of inquiry is a work in progress, and promises to enhance our understanding of disease and health. 

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