So, as we discussed previously, genomic imprinting is the phenomenon where the pattern of expression of an allele differs depending on whether that allele was inherited from your mother or your father. This difference in expression does not depend on differences in the DNA sequence of the two alleles. Your two alleles might have identical DNA sequences, but function completely differently.

For example, one of the two alleles might be epigenetically silenced. That is, because of reversible chemical modifications to the DNA, or to proteins that are closely associated with the DNA, that allele would be inactive. The other allele, with an identical DNA sequence, but different modifications, would be happily chugging along producing its gene product(s). Today’s question is, “That seems crazy! Why would you do something like that?”

One of interesting (and by “interesting” I mean “sad”) things about evolutionary biologists is that whenever something genuinely new and surprising is found in the world, everyone feels the need to propose an evolutionary explanation for it, whether new explanations are needed or not. So, many attempts to explain the origins of imprinting have been proposed, most of which are consistent with at least some of the data, and a few of which actually make sense. There is one explanation, however, that is far and away the most successful in explaining the distribution and nature of imprinted genes: the “Kinship” or “conflict” theory of imprinting. This theory owes its creation and early development primarily to David Haig (who laid out the theory originally in papers with Mark Westoby and Tom Moore).

The basic idea of the Kinship Theory is that natural selection favors different expression behaviors for maternally and paternally inherited alleles. That is, the optimal level of expression for an allele that is maternally inherited is different from the optimal level for a paternally inherited allele. Now, if you think about that for a minute, it probably seems strange. I mean, if I survive and reproduce, that’s equally good for any of my genes, independent of where I got them from, right? Right?

The key is recognizing that natural selection favors allele that pass on the largest number of copies to future generations. (“Isn’t that what I just said?”) AND, that it doesn’t matter whether those copies are passed on directly by my having children, or if they are passed on because because one of my relatives, who has inherited an identical copy of that allele, has children. There are different ways to represent this (which are all mathematically equivalent if you do them right), but the one that I find most intuitive is the idea of “inclusive fitness.” Basically, we can think of natural selection as maximizing the inclusive fitness of an allele, which is the fitness of every individual in the population, weighted by the probability that they carry the allele. In the simplest model, this probability is 1 for me, 1/2 for a sibling, 1/8 for a cousin, and so on.

Now, think about your relatives. With the exception of your descendants, your full siblings, and their descendants, all of your relatives are related to you either through your mother or your father. That means that, in general, this inclusive fitness calculation will be different for maternally and paternally derived alleles. Therefore, there will be a conflict, where the phenotype that would maximize the inclusive fitness of your maternally inherited allele will be different from the one that would maximize the inclusive fitness of your paternally inherited allele. If this difference is large enough, it can actually drive alleles to take on two different conditional expression strategies, and, voila, imprinting.

Granted, even in the most extreme cases, this difference is likely to be pretty subtle, which might make it seem strange that this could explain a situation where one of the two alleles is completely turned off, while the other one is cranking away. This phenomenon, where a little conflict leads to a big effect, will be the subject of the next installment.

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.