Genomics becomes epigenomics:
Years ago President Clinton, looking around for something to brag about, decided that the human genome project was complete. It wasn’t. It probably never will be. But he declared a victory.
The human genome is of course the DNA in the nuclei of our cells. There is a lot of it. Billions of base pairs. And everybody is different except identical twins. So it is a lot of stuff to figure out. A draft sequence had been prepared. And the study of the genome, genomics, continues to attract considerable and very expensive interest. Many problems have been worked out. The hope was that as soon as we had the test we could work out what a whole lot of genes were doing and be prepared to council people on what diseases they might get and what to do about it. The what-a-whole-lot-of-genes-are-doing part has worked out. With a few exceptions, the impact on human health has been less thrilling. (Major Heart Disease Genes Prove Elusive Jennifer Couzin-Frankel SCIENCE vol. 328 no. 5983 June 4, 2010 page 1220)
As techniques are refined and computing power becomes cheaper working out a genome for an individual has become cheaper. Within a few years they recon that they will be able to cast your genome for about a thousand dollars – cheap enough for recreational purposes for some and cheap enough for medical purposes for many. I think the real payoff may be that comparing genomes may be a way to find possible mates who are near enough kin for adequate fertility. That is still too expensive. But dedicated mass throughput automatic analyzers should some day make it possible.
Meanwhile there is a new kid on the block so to speak. (Genomics Goes Beyond DNA sequence, Alla Katsnelson, NATURE vol. 465 no. 7295 May 13, 2010 page 145) I have mentioned elsewhere that there is a field of epigenitics. If you have a gene in the form of a length of DNA, the expression of that gene is at least in part regulated by such things as having a methyl group, basically a carbon atom, tagged onto the DNA strand.
Since DNA is a double helix that must fit together properly, and since the variable and thus the interesting part of the DNA is inside the helix, changes which is to say mutations are few. But tacking a carbon atom on the outside is relatively quick and easy. So different cells in the body have different sets of methyl tags. That is part of why they are different.
Now there is more to epigenetics than methyl groups, but that is the general picture.
It has now been announced that a company called Pacific Biosciences has built a machine that will not only read out the DNA sequence but identify the methyl groups.
This will be vastly important for studying what is going on at a cellular level. As for finding kin, there is no immediately apparent advantage over the DNA genome itself.
But think back to the Long House Valley population. We watched it rise and fall twice. Over one period it reversed itself twice in five generations. That just seems too fast for DNA mutations.
But epigenetic markers are to a certain extent inheritable. And they change fast. There is an excellent article that I cannot say enough nice things about (Epigenetics as a Unifying Principle in the Aetiology of Complex Traits and Diseases Arturas Petronis of the Krembil Family Epigenetics Laboratory, Centre for Addiction and Mental Health, 2050 College Street, Toronto Ontario MST 1RB, Canada NATURE vol. 721 no. 7299 June 10, 2010 page 721) which says epigenetic changes from generation to generation are about a thousand times faster than regular DNA mutations. I like that number. If it takes a few generations for severe infertility to develop from outbreeding but it takes a few thousand generations for species to diverge, then the one process could be epigenetic and the other process genetic and the numbers come out about right.
There seems to be a general rule to science that something that is perfectly obvious on the face of it is ignored or denied until some specialist comes up with new data. For instance as I child I looked at a globe and told my teacher that it was obvious that the two sides of the Atlantic Ocean matched so they must once have fit together. She complemented me on my imagination but assured me that it was never so. Now one never seems to hear the end of “plate tectonics” and the way continents drift around on the molten rock below. Anyone who looks up on a clear night sees stars against a black background and knows at once that the universe cannot be both infinitely large and infinitely old. Otherwise there would be no dark places between stars. And it is obvious from the law of gravity that if the universe were of limited size it could not be infinitely old because it would have collapsed on itself. So there was a moment of a beginning. Yet this was not common coin in science until a man named Hubble (and his mule skinner friend and assistant) made measurements that showed the universe was expanding.
So there is ample, nay overwhelming evidence that the well documented effect of lack of kinship reducing fertility for individuals and small groups also is manifest over enormous populations. But the mechanism is lacking. It has to be there somewhere. That is most obvious. And the article by Petronis cited above may hold the mechanism. It is a very thoughtful article, suggesting that there are long overdue paradigm shifts in genetics and goes into detail about some of the evidence. I very much liked his suggestion that heredity may be like those little nested Russian dolls, one inside the other.
For instance there are inherited diseases that get worse and worse each generation. That cannot be explained by standard genetics. Also there are things like the fact that 60 % of your chance of having a heart attack is inherited. But when they have actually looked at the genes, they have only found genetic variability to account for about 5 %. Clearly there is something going on that for practical purposes is far more important than DNA, the double helix and the genetic code.
As Petronis points out, the split between heredity and environment is becoming fuzzy. An organism can acquire epigenetic changes from environmental influence and those changes can to a certain extent be inherited.
The mechanism for infertility accumulating from mating in sequential generations outside kin may be epigenetic. Epigenetic things move fast enough. They are apparently far more complex than the raw DNA that they wrangle.
Let’s hear a cheer for the new machine and for the new field
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