Puzzling over epigenetics again:
Once my brothers and I and a couple of friends were tramping in the woods accompanied by our remarkably energetic dog. The dog took an interest in a large hollow root of a big tree. There was a small fissure in the root through which a person even more foolish than I might have thrust fingers into the cavity. From the size of the root the hole might have held something as big as a squirrel or rabbit. The dog barked, sniffed at the opening and tore at the roots with her teeth with great enthusiasm. We never learned what was in there although the dog might have known. What we knew was that the dog knew that there was something in there that needed to be barked at and if possible chased.
So it is with me and epigenetic control systems: all things other than genes that turn genes on and off. Clearly the effect of kinship on fertility is regulated by some sort of epigenetic mechanism, my guess being that at least one mechanism is methylation, the binding of a carbon atom to DNA, frequently where a cytosine group sits next a guanine group. (It’s more complicated than that as I already described in an earlier post about a later paper.) Studies of methylation proceed apace. (Vivien Mark Reading the Second Genomic Code NATURE vol. 491 no. 7422 November 1, 2012 page 143)
It is possible to do a good job of sequencing DNA. It is also possible to determine just where along the DNA strands the methyl (carbon) groups are found. Figuring out just what is going on is difficult. Results are often hard to replicate. One approach is to make an antibody against some site of interest, get the antibody to attach and then analyze the site to see whether it is methylated. Alas, the antibodies are made by rabbits and they vary from rabbit to rabbit. Getting bacteria to make the antibodies hasn’t worked out, which is a pity because a colony of bacteria varies a lot less than a room full of rabbits. On top of that, methylation patterns in a cell are constantly changing. I am totally at sea and even the experts find it all rather a challenge.
Now methylation reduces gene function. Normal growth and development require turning genes on and off in a sequence that beggars analogy. Words like “orderly,” “orchestration” and “programming” come to mind, but all are like playing Nim compared with what is going on in the cell. It all begins to make sense. My brother came back from Harvard and explained existentialism to us. As we made heavy weather of understanding it my father cheerfully suggested, “It’s existentialism when you think it’s just about to make sense and then suddenly it doesn’t.” You just methylate everything and then some clue from the environment (meaning adjacent cells in this case) comes along and causes demethylation of the appropriate genes. But alas only about 1% of the DNA is capable of getting sufficiently methalyated anyway. (Dirk Schübeler Epigenetic Islands in a Genetic Ocean SCIENCE vol. 338 no. 6108 November 9, 2013 page 756) And somehow it’s got to do with RNA.
I used to think I understood RNA. At least I though somebody understood it. There was m-RNA, messenger RNA, that carried the genetic information from the DNA of the nucleus to the mitochondria out in the cytoplasm. There was t-RNA, transfer RNA, that would pick up an amino acid and bring it to the mitochondrion. And there was m-RNA, mitochondrial RNA, from which the mitochondrion was made. Together this team could take information from the nucleus and turn it into a protein in the cytoplasm, but … well what you really have is called a polypeptide. It generally isn’t a protein until you hook up a number of polypeptides. And then the thing has to be folded properly and then edited after the fact. But we are still refining the mechanism. The whole thing gets knocked into a cocked hat when it turns out that RNA is doing a lot more. Only a tiny amount of the nuclear DNA is actually encoding genes. There is much more non coding DNA. And yet most, maybe 90 % of the DNA gets transcribed into RNA. And then any one gene may get transcribed or get transcribed with varying amounts of non coding DNA on the average of 10 times (Jeannie T. Lee Epigenetic Regulation by Long Noncoding RNA’s SCIENCE vol. 338 no. 6113 December 14, 2012 page 1435) and then that regulates genes.
I swear it’s enough to make a man gnaw roots or turn to existentialism.
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