Lick Your Rat Pups: Epigenetics, Methyl Groups, DNA, Evolution

Can behavioral change of a parent be passed on to children and grandchildren?  Darwinian evolution would say no.  But scientists today are finding this a lot more complicated. 

Think of this post as some notes to myself.  I don't even remember what caused me to google 'epigenetics.'  I'm a little behind the curve on this, but I suspect I'm not the only one.  And it seems like something I should know more about.  Here are some tantalizing quotes in fairly understandable English. 



From Discover Magazine:

"Until researchers like Razin came along, the basic story line on how genes get transcribed in a cell was neat and simple. DNA is the master code, residing inside the nucleus of every cell; RNA transcribes the code to build whatever proteins the cell needs. Then some of Razin’s colleagues showed that methyl groups could attach to cytosine, one of the chemical bases in DNA and RNA. 

It was Razin, working with fellow biochemist Howard Cedar, who showed these attachments weren’t just brief, meaningless affairs. The methyl groups could become married permanently to the DNA, getting replicated right along with it through a hundred generations. As in any good marriage, moreover, the attachment of the methyl groups significantly altered the behavior of whichever gene they wed, inhibiting its transcription, much like a jealous spouse. It did so, Razin and Cedar showed, by tightening the thread of DNA as it wrapped around a molecular spool, called a histone, inside the nucleus. The tighter it is wrapped, the harder to produce proteins from the gene."

From the University of Utah

These records showed that food availability between the ages of nine and twelve for the paternal grandfather affected the lifespan of his grandchildren. But not in the way you might think. Shortage of food for the grandfather was associated with extended lifespan of his grandchildren. Food abundance, on the other hand, was associated with a greatly shortened lifespan of the grandchildren. Early death was the result of either diabetes or heart disease. Could it be that during this critical period of development for the grandfather, epigenetic mechanisms are "capturing" nutritional information about the environment to pass on to the next generation?

From Epigenome:

"Male lions are among the most sexually active of mammalian beasts. In captivity they have even been known to mount female tigers. The resulting liger offspring make their parents look like pussy cats, often exceeding twelve feet in length and doubling parental weight. In contrast, if you mate a male tiger with a female lion, the resulting tigon is considerably smaller. What makes the liger so big and tigon so small?"

From the Johns Hopkins Center for Epigenetics Website:

Understanding how the information in the human genome is utilized is one of the central questions in modern biology. It has become clear that a critical level of gene regulation occurs through the chemical modification of both the DNA itself and the proteins that organize eukaryotic DNA into chromatin. This form of gene regulation, termed epigenetics, refers to cellular "memory" other than the DNA sequence alone, and occurs through mechanisms such as the addition of methyl groups to DNA, as a way of marking specific genes as active or silent. The Center for Epigenetics has brought together investigators in genetics, biochemistry, cell biology, biostatistics, epidemiology, and clinical medicine to develop new technologies to apply to both basic science and population-based epigenetic studies. The center has developed several new genomics, biostatistical, and biochemical methods and is applying them to cutting-edge studies of epigenetic mechanisms and disease research.

From Radio Lab:

As we reported, the duo's lab work shows that when a mother rat licks a pup (her sign of "I love you"*), the action sets off a Rube Golberg-esque cascade of hormones, which ultimately wind up all the way down at the level of the DNA.

Image from Radio Lab

What do those hormones do down there? It turns out, they change the chemical markers, or epigenome, surrounding certain areas of the DNA. And the end result of these changes hinges on how much the rat pup is licked: if a rat pup gets a lot of licks, the epigenetic changes cause the pup to grow up and lick its own kids a lot; if a pup doesn't get a lot of licks, the chemical changes cause that pup to be a low-licker. In both cases, the pattern of maternal behavior is carried across generations -- from grandmothers to mothers to grandkids. Or, in the words of Radiolab producer Soren Wheeler, "It's as if the epigenetic information leaps up out of the mother's genes through a tongue and lands back on the babies' genes." (Interested? Go listen to the show for more!)

From Science we get warned about calling every nongenetic system as epigenetic:

"The cells in a multicellular organism have nominally identical DNA sequences (and therefore the same genetic instruction sets), yet maintain different terminal phenotypes. This nongenetic cellular memory, which records developmental and environmental cues (and alternative cell states in unicellular organisms), is the basis of epi-(above)–genetics.

The lack of identified genetic determinants that fully explain the heritability of complex traits, and the inability to pinpoint causative genetic effects in some complex diseases, suggest possible epigenetic explanations for this missing information. This growing interest, along with the desire to understand the “deprogramming” of differentiated cells into pluripotent/totipotent states, has led to “epigenetic” becoming shorthand for many regulatory systems involving DNA methylation, histone modification, nucleosome location, or noncoding RNA. This is to be encouraged, but the labeling of nongenetic systems as epigenetic by default has the potential to confuse (see the related video at www.sciencemag.org/special/epigenetics/)."

I don't know what this all means yet.  As I said, notes to myself.