25 June 2012
Yesterday I had lunch with my grandpa at a very nice outdoor Cafe down in La Jolla. He reflects a keen intellect and curious disposition sharpened by more than eight decades of life experience. A social man, he has garnered many friends of similar curiosity in his community. Whenever we meet up for lunch it is early impossible not to run into people he is familiar with, and I often have the pleasure of meeting more experienced curious minds.
Shortly after introducing me to yet another one of his friends, I had the pleasure of having an impromptu conversation on the revelations (and subsequent mysteries presented) by a certain major find of the late 20th century: more or less, all of the cells in our bodies have the same genomic DNA. What Milt wanted to know, was why?
Fundamental questions are often framed under: Who What When Where Why and How? When it comes to the natural world (of which we are a part) it is the Why that is perhaps the most perplexing.
Almost all of the cells in our bodies have the same sequence of genomic DNA. There are some exceptions, of course: our cells also have a certain amount of DNA housed in mitochondria, and some cells, like red blood cells, contain no nuclei and no genomic DNA. Although we all contain DNA sequences that differ slightly from person to person, within an individual almost all of the trillions of cells in the body have the same DNA sequence. With all the different cell types that exist, how can this be?
One answer to that question is epigenetics. Literally, epi- (above) genes. Imagine a book that contains 300 pages. We’ll title this book “Genomic DNA.” In the basal skin cell edition, pages 50-67, 103-245 and 278-290 are all glued together and cannot be read. In the muscle cell edition, pages 23-60, 98-110, and 115-250 that are glued together and cannot be read. The list goes on. Although all of the books for the various cell types technically contain the same code, not all of the code can be read. This is true for genomic DNA: processes like methylation and acetylation allow preferential reading of certain sections of the code. It is the pattern of these processes that varies between cell types.
But, this does not quite answer the “Why?”
Milt asked, if there are parts of the genome that are not useful for, say, a skin cell, why keep it around? Surely it must have taken a lot of energy and cellular resources to write all those pages that cannot be read, and the extra space in a cell it takes up could be used for something else?
While it might be impossible to come up with an unequivocal answer for that one, I would like to remind my dear readers that there are no absolutes in science: there are only greater levels of certainty. There is rarely any true black or true white, but many, many shades of gray in the emerging picture of biological systems, and this picture is subject to change as we gain more data about the world.
What I can offer is the best possible explanation given what we know about biological systems. And that answer is fairly simple: natural selection demands adequacy, not perfection.
Above is an image of a man-made circuit. Below is an image of an evolution-made circuit. Natural selection rarely produces something de novo. Usually, it takes something that already existed (like a particular protein) and tweaks it in slight ways that allow it to fill additional or unique roles. It would be like building a house one room at a time without a master plan. As such, biological circuits tend to be very disorganized and contain a high amount of redundancy: they make that multiple outlet adapter with the cords to your computer, screen, printer, fax, etc look orderly and neat by comparison.
At risk of sounding circular, you and I tend to think like humans. Humans like to organize thoughts into categories and streamline processes. The best humans esteem perfection. Natural selection does not produce perfection, it produces survival. Natural selection’s attitude is: if the shoe fits, wear it. Don’t fix something that’s not broken.
Looking deeper into other cellular processes, one begins to find many examples of energetically expensive or redundant cellular pathways. Perhaps there is a reason to keep all those glued together pages in that book? Maybe it would take too much effort and energy to remove them? Maybe removing them would risk damaging adjacent pages that need to be read correctly to make a skin cell and not a skin cancer?
Again, there is no absolute answer to the question of WHY all of our cells contain the same DNA if not all of it is used. But, I hope that this blog entry helps to explain some of the nuances and depth to this mystery.