More Genetic Conflict

I have posted before on my miserable pregnancy and delicately blamed my darling little girl for it. But she's cute, and I like her, so I really can't blame her for anything. Her father though..... Brian's wonderful, an amazing father, and truly supportive. He's also cute too. But I just read an article that suggests that he might have a darker side. You see, it might have been overexpression of his genes in the placenta that led to my crummy pregnancy. It's also possible that underexpression of genes derived from my side were at fault, but let's not blame the victim.

At first, it doesn't seem that the idea that expression of genes in the placenta can depend on which parent they came from would be revolutionary, but if you think about it for a minute, you can see that Mendelian inheritance cannot explain why this should happen. A gene coding for, say, development of an eyeball codes for the development of an eyeball, regardless of whether it came from the father or the mother. Outside of the sex chromosomes, there is nothing in the genome that tells the infant which parent it was derived from. However, you can see how from a Selfish Gene perspective this could be useful - what if you were a male, and decided that the death of the mother wasn't a big deal if you got a healthy baby that carried half your genes? Hopefully, if you were a human male, you'd be thrown in jail and sterilized for such behavior. However, nature is red in tooth and claw and if you're a gene, then such an influence might spread - but only if it was always passed from the male. This requires a way to temporarily modify gene expression, to turn a gene on only if it is derived from the father. A genetic change that is lasting enough for a generation, but not any more. This is done by epigenetic modification of the DNA.

In order to understand why epigenetic inheritance is so weird, and so revolutionary to the field of genetics, we have to go back to the Origin of evolutionary theory - pardon the pun. Before inheritance was completely understood, there were two major competing theories as to how evolution happened. We now understand that genes are the mode of inheritance. We know that they are inherited from our parents, and while smoking or sunburns might result in random mutations, there is no way that we can alter our genome to affect our future generations. This is in contrast to the idea that an individual may acquire characteristics during their lifetime that may be passed on to their offspring. The most famous example of inheritance of acquired characters, or Lamarckian inheritance, is the idea that the giraffe got its long neck by stretching its head to reach leaves. Thus a giraffe that really stretched its neck out would have offspring with long necks as well. This theory, proposed by Jean-Baptiste Lamarck, was disproven by August Weismann in the 1880s, when he showed that inheritance is only possible through the gametes (egg and sperm), as opposed to somatic cells (cells everywhere else). Thus any changes to cells within the body cannot be passed on to the germ cells.

This was the understanding of genetic medicine for years. Genetic disorders are possible, but arise and evolve over thousands of generations due to the breeding success and failure of thousands of individuals. However, a seminal series of papers collectively called the Overkalix study showed how experiences in individual's lifetime could result in disease within one or two generations. In the Overkalix parish in remote northern Sweden is a population that has endured repeated sudden famines, and equally sporadic bumper crops, over the last two hundred years. The study showed that if a boy during experienced a period of plenty during his preteen years, his grandson was more likely to die of cardiovascular disease. This goes against everything we know about Mendelian inheritance: the effect is within two generations, and is only passed along males.

This sounds suspiciously like Lamarckian inheritance. In fact, in this case inheritance is mediated not by changes to the genetic code, but changes to the proteins associated with a string of DNA, or by epigenetic changes. The environment can trigger changes to the proteins that fold DNA, or cause chemical tags to be added to the DNA backbone. Either of these DNA modifications can "imprint," or change the expression of certain genes, and in the case of epigenetic inheritance, can alter how genes are expressed in subsequent generations.

In the case of preeclampsia, the disorder is likely caused by imperfect imprinting. Preeclampsia is a disorder that affects 3-7% of pregnancies, and is characterized by an increased blood pressure and protein in the urine. Left untreated, it can develop into HELLP disorder, which stands for Hemolytic anaemia, Elevated Liver enzymes, and Low Platelets, which can cause seizures and death of the mother. Preeclampsia is often inherited maternally, which suggests that the problem comes down the female side, but there are also paternally derived genes that have been implicated. So when it comes down to it, there is no way to determine whether my crappy pregnancy was the fault of Brian's genes or mine. But I am definitely heartened by the fact that if I had to have a disorder, at least it was a genetically interesting one.