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Naples VL, Rothschild B (2017) The Complexity of DNA Transcends Epigenetics. Rheumatica Acta: Open Access 1(1): 004-005. DOI: 10.17352/raoa.000002Availability of new has afforded rheumatologists the opportunity to investigate molecular pathophysiology of joint disease techniques [1,2]. Attempts to relate DNA polymorphisms to disease activity or addresses one aspect susceptibility [3-5]. Mutations and epigenetics have received consideration [3,6], but there is another pertinent concept that needs a clearer definition when seeking to understand synovial pathophysiology and that is pleiotropy. This concept is not frequently discussed and its significance and implications, rarely recognized. Epigenetics is the alteration of gene function in an organism, but not of the gene itself [7-11], (Reik, 2007). This is in contradistinction to pleiotropic effects, variable somatic changes induced by a single gene often simultaneously, but differentially affecting multiple body systems [12-14].
The genomes of an increasing variety of organisms have been studied in sufficient detail so that trait-coding genes are often specifically localized on chromosomes [15]. Merely because a given gene is present, however, does not mean the information it contains will always be transcribed. Even if transcribed, the process does not necessarily involve the entire gene, but may be limited to only select sequences. Which portions subjected to selection is organ- and sometimes tissue-dependent. Thus, changes in functional morphology do not necessarily require a change in the DNA sequence. Perhaps the effectors of the resultant functions are analogous to allosteric effects on enzyme function [16-18]. These are of great importance because they alter the shape of the DNA molecule, changing the components that are accessible to transfer (t)-RNA transcription.
Traditional thinking suggests that transcription begins with an initiation sequence of several nucleotides, and that the t-RNA continues to move along the full length of the gene until reaching a termination sequence. However, transcription of segments of genes does not always use this mechanism. This difference may be part of maintaining the fidelity of DNA replication, but not necessarily the transcription of separate components of the gene.
Although there may be more than a single DNA sequence that that can be translated into a specific protein, only a limited number of variations will allow for the generation of the correct three-dimensional product [12,14,19]. If the incorrectly copied instructions are accurate enough that a substitute t-RNA is generated, it may not work well or at all. At the least, it is likely to have an altered tertiary shape. The new shape is likely to cause a change or failure of function. In fact, many such molecules that show altered shapes might not be able to fold themselves into units that are functional enough that they are capable of accomplishing the task for which they are intended to code [20].
Another area that has not received as much attention is the number of copies of the gene present in the full organism genome. A most timely example relates to the p53 locus, important in the biochemical pathophysiology of cancer [21-23]. The rarity of cancer in elephants may well be related to their possession of 20 separate chromosome sites (double-stranded DNA providing 40 copies) of the gene responsible for coding this function [24]. What we don’t yet know is whether all copies are active or whether their behavior reflects their neighborhood (surrounding gene activators and suppressors – the “deciders” Finally, we are left with the question: How much of functional morphology reflects nature (the genome sequence) and how much is a product of “nuture.” (The environment in which the gene finds itself).
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