Back again for its second week in a row is the Science Pick of the Week.
This week's article is titled "Rethinking the Genetic Theory of Inheritance: Heritability May Not Be Limited to DNA," and can be found here
. The abstract of the actual publication from Nature Genetics
is located here
. Read up!The Long and Short of It:Epigenetics
is a burgeoning field in biology that studies mechanisms of inheritance that aren't directly related to DNA sequence. This field has been around for a while, but research on the subject is just now picking up steam.Background:
In our survey of epigenetics, we'll begin with the word itself: The prefix "epi" means "above," or "outside." So, molecular mechanism of heritability that isn't based on DNA sequence is outside the realm of traditional genetics, and is thus epi-genetic. Lost? Here's a metaphor: I want to send a package of cleaning supplies to a friend. The post office, however, will not allow me to send them through the postal service. I must therefore use an "epipostal" means of delivering my package to my friend - perhaps by means of another friend, or a private delivery service.
So, epigenetics describes any way of delivering information from parents to offspring, apart from the ATGC base sequence of DNA. The first, most well-known epigenetic method of heritability is DNA methylation
remodeling. To help us understand methylation and histones, I'm going to use a metaphor. Imagine you are employed at a large warehouse, full of boxes stacked to shoulder height. All of the boxes have latches, and each box is linked to two adjacent boxes to form one continuous chain. The warehouse manager will want access to the contents of certain boxes at certain times, and it is your job to unstack, re-stack, and unlatch the requested boxes when called.
Now, to translate our metaphor to science: The warehouse is the nucleus of a cell and the boxes are histones, which package portions of your DNA. When that DNA is needed for transcription
, it must often be unpacked. The latches on the boxes are methyl groups, which hinder effective transcription by binding the DNA closely to the histones and interfering with replication machinery. These methyl groups must be removed from the DNA before it can be read by RNA polymerases
, which carry the information from the DNA, from the nucleus, to the cytoplasm
or endoplasmic reticulum
, to create proteins. Going back to the metaphor, by unhooking the latches from a box, you would be serving as a methyltransferase, an enzyme that removes the methyl group from the DNA, allowing the DNA to pull away from the histone enough to be read by an RNA polymerase.
DNA methylation and histone remodeling are necessary for arranging the DNA in the nucleus, and these methylation patterns are transmitted to daughter DNA strands when the DNA is replicated. Thus, if a gene is turned off by a series of methylations, each of the two DNA strands resulting from replication will have roughly the same methylation pattern, and the gene will likely be turned off in both these strands. In this way, a predisposition toward certain genes being turned off or on can be passed to offspring.
The second currently-known mechanism of epigenetic inheritance are RNA transcripts. Many genes produce a product that influence the future expression of that gene. This product (either RNA or a protein) can also be transmitted to neighboring cells, influencing gene expression there. In the case of inheritance, the mother donates a lot of RNA and protein during the formation of the egg. The fertilizing sperm also contributes a small amount or RNA and protein, which may also play a role in epigenetic inheritance.
This leaves us two final mechanisms of epigenetic inheritance: prions and structural inheritance. Prions are malformed proteins that can cause correctly-formed proteins of the same kind to form dysfunctional clumps. Think of it like peer pressure: Prions are the charismatic bad boys, leading hopeless hordes of functional proteins astray. These protein clumps form other, bigger clumps, interfering with the work of that protein, and often causing damage to the cell. How bad is that? Well, mad cow disease is caused by prions. If a parent is suffering from a prion disease, chances are, some of those malformed protein clumps are going to make it into the germ cells of the next generation, which make prions an epigenetic carrier of disease - if the offspring survives long enough to notice.
Structural inheritance is the last a least well-known mechanism of epigenetics. This method of inheritance is inferred from studies done on ciliates. In these studies, the researchers experimentally altered the pattern of cila on the organism, and observed that the changes they made were transmitted, more or less, to offspring. There isn't a lot of information out there yet about how this works. It boils down to, "We changed something, without changing the DNA, and the changes were inherited." It seems reasonable to assume that when cells divide, existing structures in the cell are used as templates for new structure.Findings and Significance:
Now, those of you who are mildly acquainted with science may be thinking, "Wow, this is really neat! To think that there's something other than DNA that influences our natural development! And to think we just now figured it out, a century-and-a-half after Mendel
laid the foundation for genetic research!" But, if everything that I just wrote about had been figured out in one study, there would have been more than a ScienceDaily article about it. Those of you who have been in science for a while know that this article is written to be a lot more sensational than it really is. Epigenetics is nothing very new in science. Papers about it were being published way back in the late 80s
and early 90s
. I was taught about it in my undergraduate genetics course.
This study is significant for two reasons: It supports previously-established scientific theory, and makes an attempt to catalogue differences in DNA methylation between monozygotic and dizygotic twins. Another, very similar study was completed back in 2005 ("Epigenetic Differences Arise during the Lifetime of Monozygotic Twins" full text
), though in that study the researchers did not characterize methylation patterns as extensively.
This article is old news. For all the excitement and cutting-edge language used in the article and by Dr. Petronis (the author of the referenced study), most of he found had been found 3 years earlier. Why did ScienceDaily run this article now? Maybe Dr. Petronis has some sway, or is more well-known than the 2005 researchers. Perhaps the article writer just wasn't familiar with epigenetics. Whatever the case, it gave us a good opportunity to briefly explore one of the modern offshoots of heritability and genetics. My hat is off to Dr. Petronis for scientific rigor and for bringing new data regarding DNA methylation patterns. See you next week!