GENOMIC IMPRINTING

DAVID HAIG: My work over the last decade or so has been principally concerned with conflicts within the individual organism. In a lot of evolutionary biology, the implicit metaphor is that the organism is a machine or, more specifically, a fitness-maximizing computer trying to solve some problem. Maximizing fitness is analogous to maximizing a utility function in economics. I'm interested in situations where there are conflicts within the individual, in which different agents within the self have different fitness functions, as well as the internal politics resulting from those conflicts of interest.

The area to which I've given the greatest attention is a new phenomenon in molecular biology called genomic imprinting, which is a situation in which a DNA sequence can have conditional behavior depending on whether it is maternally inherited—coming from an egg—or paternally inherited—coming through a sperm. The phenomenon is called imprinting because the basic idea is that there is some imprint that is put on the DNA in the mother's ovary or in the father's testes which marks that DNA as being maternal or paternal, and influences its pattern of expression—what the gene does in the next generation in both male and female offspring.

This is a complicated process because the imprint can be erased and reset. For example, the maternal genes in my body when I pass them on to my children are going to be paternal genes having paternal behavior. If my daughter passes on paternal genes to her children, even though she got the gene as a paternal gene from me it would be a maternal gene to her own offspring. Molecular biologists are particularly interested in understanding the nature of these imprints, and how it is possible to modify DNA in some way that is heritable but can then be reset. My own interest has been understanding why such odd behavior should evolve. I've been trying to find situations in which what is best for genes of maternal origin is different from what maximizes the fitness of genes of paternal origin.

The best way to understand the underlying theory is with a famous anecdote accredited to J.B.S. Haldane, the great British geneticist, who is said to have claimed that he would give his life to save more than two drowning brothers or more than eight drowning cousins. The logic is that if Haldane is only concerned with transmitting his genes to future generations, this is the right thing to do. On average, a gene in his body has one chance in two of being present in a brother. If he sacrificed the copy of a gene in his body to rescue three brothers, on average he'd be rescuing one and a half copies of the gene in his three brothers; placing him ahead in the genetic accounting. But when it comes to cousins, each only has one chance in eight of carrying a random gene in Haldane's body. To benefit from the sacrifice of one copy of a gene in himself, he needs to rescue nine or more cousins. This was formalized by Bill Hamilton in his theory of inclusive fitness.

My theory can be illustrated by rephrasing Haldane's question and asking: Would Haldane sacrifice his life for three half-brothers? For the sake of the story let's say that these are his maternal half-brothers—offspring of his mother but with different fathers. The traditional answer to that question is no, because if you pick a random gene in Haldane, it's got one chance in four of being present in a half-brother. Thus, a random gene would have an expectation of rescuing three quarters of a copy—three times one quarter—for the loss of one copy in Haldane. However, if imprinting is possible, genes may have information about their parental origin, and this can change the accounting.