Genomic Imprinting I

So, one of the things that I study is genomic imprinting. What is that, exactly?

Even if you're not a biologist, you are probably familiar with the fact that, for most of your genes, we carry two different copies, or alleles. You get one of those alleles from your mom, and one from your dad. Those two alleles could be the same (have identical DNA sequences) or different (usually only at a small number of positions within DNA sequence). If they are different, then the consequences of those alleles on your traits, like how tall you are or what color your eyes are, are determined by the dominance relationship between those two alleles. For example, the main allele responsible for red hair (at the MC1R locus) is recessive in relationship to alleles for brown or black hair. So, if you have only one copy of the red-hair allele, you will probably have dark hair. Importantly, in terms of what follows, it does not depend whether the recessive red-hair allele you have came from your mother or father.

If you are a biologist, you already knew all of that, but you may or may not be familiar with imprinted genes. About one percent (or possibly more) of our genes are imprinted. For these genes, it does matter which allele came from your mother and which one came from your father. That's because imprinted genes retain a chemical memory of which parent they came from, and function differently depending on their parental origin. More specifically, at an imprinted locus, alleles are subjected to epigenetic modifications in the germ lines (ovaries or testes). These epigenetic modifications can be chemical modifications applied directly to the DNA itself, or modifications to proteins that are closely associated with the DNA. These modifications alter how the allele functions, without modifying the DNA sequence itself. The key thing is that, for imprinted genes, the epigenetic modifications that are established in the male germ line are different from those established in the female germ line. So the allele that came from your father will function differently from the allele that came from your mother, even if the DNA sequences are identical.

In the simplest cases, one of the two alleles is inactivated, or turned off. The effect of that gene on a given trait, then, depends only on the active allele. To return to the red-hair example, imagine that the MC1R locus was imprinted (which it is not, as far as we know), and that only the paternally inherited copy was expressed. Now, if you had one copy of the red-hair allele, and one of the more common dark hair allele, you would not necessarily have dark hair. Your hair would be dark if your red-hair allele came from your mom, but if it came from your dad, your hair would be red.

Of course, as with all things in biology, once you start looking at the details, everything becomes a lot messier and more confusing. But, that is the basic gist.

Genomic imprinting was one of the biggest surprises to come out of molecular biology in the past few decades. Both the origins of imprinting of particular genes, and the effect of imprinting on the evolution of those genes, are interesting questions that we will return to in future posts. At some point along the way, we will get deeper into those messy and confusing details.