Manuscript II - Planning part 2

In the last post I came up with a number of questions that I an address with my data set, but in the end, I have at couple compelling hypotheses that I can test which should be the focus of the paper.

Here is the first hypothesis:

Many imprinted genes are growth factors that act in a dosage-dependent manner. Abnormal growth is the result of increased expression of genes which promote or repress growth. Abnormal growth manifests in a parent-of-origin manner when one hybrid type exhibits increases in growth promoting genes and the reciprocal hybrid exhibits increases in growth repressing genes.

The common trait to all hybrids, large or small, is that genes which regulate growth show increased expression level. If these genes promote growth then the individual is large, if these genes repress growth then the individual is small. Furthermore, we predict that when imprinting is disrupted, the gene which should be expressed from a single allele is actually expressed from both alleles. This should result in a doubling of expression level.

We can test this hypothesis by looking at expression level in large hybrids and comparing it with small hybrids. If growth promoting genes are expressed from two alleles and show increased expression level in large hybrids then this hypothesis would be supported.

The second hypothesis is this:

There is ample evidence that hemizygosity is bad as it exposes things which are deleterious but recessive. This is probably most clear when we look at the X chromosome. One of the main reasons for Haldane's rule (the disproportionate affliction of incompatibilities in males) is that males have a single copy of the X while females have two X chromosomes. Thus, females are able to mask recessive deleterious things on the X but males are not. As imprinted genes are similarly expressed from a single copy, all recessive incompatabilities involving them will be exposed. Furthermore, in the reciprocal hybrid, the alternate allele is expressed which should ameliorate the incompatibility.

This hypothesis is mute with respect to dosage, and can occur whether or not the dosage of different alleles is disrupted.


I think that the paper will start by addressing these two hypothesis and set up a framework for how to test each using the growth effects in the hamster hybrids.