13 October 2010

A Hint of Epigenetics

The term “epigenetics” most commonly refers to heritable changes in gene activity not accounted for by alterations or mutations in the DNA sequence. But in order to understand the important developments now underway in biology, it’s more useful to take “epigenetics” in its broadest sense as “putting the gene in its living context.” _NewAtlantis
Epigenetics -- non-coding control over gene expression -- is one of the most exciting areas of science at this time. We are learning that the genetic code is only the short, first chapter in a very long book. The non-genetic "code" -- the non-coding DNA and RNA -- has a logic all its own. We are just beginning to decrypt the obscure cipher. The possibilities for the transformation of life as we know it seem just as grandiose as were the hopes of the early promoters of the human genome enterprise. Only this time, we are working at a deeper level of sophistication. How many more levels will we need to descend before we reach the promised land of genetic medicine?
... some 95 or 98 percent of human DNA was useless for making proteins. Most of this “noncoding DNA” was at first dismissed as “junk” — meaningless evolutionary detritus accumulated over the ages. At best, it was viewed as a kind of bag of spare parts, borne by cells from one generation to another for possible employment in future genomic innovations. But that’s an awful lot of junk for a cell to have to lug around, duplicate at every cell division, and otherwise manage on a continuing basis.

...As organisms rise on the evolutionary scale, they tend to have more “junk DNA.” Noncoding DNA accounts for some 10 percent of the genome in many one-celled organisms, 75 percent in roundworms, and 98 percent in humans. The ironic suspicion became too obvious to ignore: maybe it’s precisely our “junk” that differentiates us from water fleas. Maybe what counts most is not so much the genes themselves as the way they are regulated and expressed. Noncoding DNA could provide the complex regulatory functions that direct genes toward service of the organism’s needs, including its developmental needs.

...Over successive generations, cells destined to become a particular type lose their ability to be transformed into any other tissue type. And so the path of differentiation leads from totipotency (the single-celled zygote is capable of developing into every cell of the body), to pluripotency (embryonic stem cells can transform themselves into many, but not all, tissue types during fetal development), to multipotency (blood stem cells can yield red cells, white cells, and platelets), to the final, fully differentiated cell of a particular tissue....Cells of the mature heart and brain, then, have inherited entirely different destinies, but the difference in those destinies was not written in their DNA sequences, which remain identical in both organs.

... _NewAtlantis

The author goes on to describe several ways in which gene expression can be drastically altered by other means than the coding of genes -- specifically by non-coding DNA and by protein :: DNA interactions. Non-coding DNA appears to play a huge role in gene expression -- as does non-coding RNA.
The ongoing discoveries of a previously-hidden epigenetic oversight of gene expression, is exciting. Yet, it is the epigenetics (and epi-epigenetics) that remain undiscovered which hold the keys to the mysteries that confound us.

The ability to reach into the subtle mechanisms of gene expression -- without mucking everything up -- will mark the beginning of a new phase of human existence.

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