You and your puppy are getting ready to play with a frisbee on a warm spring morning. As you begin the game, your nerve cells convey instructions to your muscle cells, which initially contract, and then lengthen as you release the frisbee. As your dog leaps to catch the frisbee, her muscle and nerve cells are also hard at work, and epithelial cells in her intestines are absorbing nutrients from her breakfast, ensuring that she’ll be well nourished for the day’s adventures. As you await your pup’s return with the frisbee, your skin cells are busy synthesizing Vitamin D, which helps your bone cells to gather the calcium that keeps your skeleton strong.
With such a large number of different cell types involved, a fun game of frisbee is, biologically, quite complex. All the more impressive is that there are very few genetic differences among the cell types that perform such diverse functions*. That is, if you were to compare the entire DNA sequence from one your nerve cells and to the entire DNA sequence one of your muscle cells, you’d find them to be nearly identical; the same would be true if you compared DNA from one of your dog’s nerve cells to DNA from one of her muscle cells.
While each one of your cells has the same genetic instruction manual needed to make every one of the ~20K different proteins, each cell must make only the subset of proteins needed to perform its own special function. The field of epigenetics --- whose name, literally, means “on top of genetics” --- seeks to understand how individual cell types learn and remember how to use these identical genetic instruction manuals to produce the specific subset of proteins appropriate for their individual functions.
Part of the explanation seems to be that mammalian genomes have on/off switches that help to control which parts of the genetic instruction manual are used in a given cell type. This set of states is passed on as a cell divides to produce more cells over the lifetime of an individual.
You and your dog are each estimated to lose ~30,000 skin cells everyday. Those lost cells are replaced by new skin cells whose epigenetic on/off pattern carries information about the specific subset of genes needed to make the proteins used by skin cells. Nerve, muscle, intestinal, and bone cells, too, each have and pass along to their descendant cells the distinct patterns of on/off states needed to make their own specific subsets of proteins.
I study DNA methylation, which is one of the several types of chemical on/off switches that encode epigenetic information. When a given part of the genetic instruction manual is covered with methylation, that section crumples up, such that the cell no longer has access to it, and cannot make the protein encoded there.
For many, perhaps most, genes, the on/off state in a given cell type is determined soon after conception. But it is now becoming clear that for another subset of genes, on/off states can remain flexible until later in life, leaving open the opportunity for an individual’s environment and experiences to impact which genes are active, and thus which proteins are made, in a given cell type.
Inspired by this possibility, Kathryn Lord, a fellow lab member, and I are embarking on a project to investigate whether genes relevant to behavior are among those that remain sensitive to the environment after an individual is born. Previous results from mice and rats indicate that how a rodent mom interacts with her daughters can impact the methylation state of a gene that can impact their own behavior when they go on to become moms.
Could it be that dogs, too, have genes whose on/off states are influenced by experiences in puppyhood or later? To find out, Kathryn and I are collecting saliva samples from puppies as they progress from newborn to twelve weeks, and tracking potential shifts the methylation states of genes that have the potential to impact behavior.
As is true at the outset of any scientific study, we’re not yet sure what we’ll find! If it turns out that some genes have on/off switches that are still in flux many weeks into puppyhood, it may be that a game of frisbee not only depends on epigenetic information, but can shape epigenetic information, too!
*Cells in the immune system offer a very interesting exception to this rule. We’ll address that in an upcoming post.