Genes aren’t Everything

However, what if there is something more than genetics and environment? Could there be something else that affects an organism’s traits? Vicki R. Nelson and her colleagues decided to investigate this question in a rather elegant way, and the results they obtained were rather surprising.

In a paper published in Epigenomics, Nelson and colleagues report on experiments they did with mice. They looked at two strains of mice. The first strain was essentially the “control,” and the second strain consisted of mice from the first strain, but the males’ Y-chromosomes had been replaced with a Y-chromosome from a different strain of mice. This strain is, not surprisingly, called a “chromosome substitution strain” (CSS).

So think about what they have here. They have two strains of mice. Within each strain, the females are genetically identical, and the males are genetically identical. When you compare the two strains, the only difference between them is that the males of the second strain (the CSS strain) have a different Y-chromosome from the males of the first strain.

They then bred the mice of the CSS strain with one another and looked only at the daughters that resulted from the breeding. Now think about these daughters. They are daughters because they received an X-chromosome from the mother and an X-chromosome from the father. The Y-chromosome that had been substituted does not appear anywhere in their genomes. Thus, the daughters of the mice in the CSS strain are genetically identical to all the females of the control strain.

Now what would you expect to see when the traits of these daughters are compared to the traits of the females in the first strain? Genetically, the mice are identical to one another. Thus, their traits should be incredibly similar, right? Wrong! The authors found many traits (both physiological and behavioral) that were quite different among these genetically-identical mice. They also spent a lot of time in the analysis trying to “weed out” environmental effects. In the end, the authors are convinced that many of the differences between the genetically-identical mice are explained by the fact that some of them were fathered by mice with a different Y-chromosome, even though none of them received that Y-chromosome!

The authors call this a “transgenerational genetic effect.” They say that their study clearly shows there is a transgenerational mode of inheritance that is different from the standard genetic mode of inheritance. Obviously, many traits are strongly affected by the genes that are inherited from the parents. However, the authors claim their study shows that some traits are affected by genes that are not inherited!

Here’s something even more surprising. The authors claim that when they compared the transgenerational genetic effects they saw in their study to the effects that occur when mice actually have different genes for those traits, they found that the transgenerational genetic effects were just as important.

In several strain combinations, physiological and behaviorial tests for hundreds of traits showed unequivocally that transgenerational and conventional genetic effects are remarkably similar in frequency and strength.

How in the world can genes from the father that aren’t even inherited by the daughters have an effect on the daughters? Furthermore, how can they be as important as the genes that are actually inherited? The authors list several possibilities. Small organic units called “methyl groups” are added to an organism’s DNA throughout its life. This is called “methylation.” It has an effect on the organism and would be inherited by its offspring. In addition, DNA is packaged and ordered by proteins called histones, which can be modified over the course of an organism’s life. This also has an effect on the organism and could be inherited by the offspring.

However, the authors seem to be more interested in the idea that it is related to RNA molecules. RNA molecules used to be thought of as just “carriers.” They either carry the information from DNA to the ribosomes so the cell knows how to make a protein (messenger RNA), or they carry amino acids to the ribosomes so that the protein can actually be put together (transfer RNA). More recently, however, RNA molecules have been implicated in many other processes, including gene regulation. It is possible that RNA controls a mode of inheritance that we have not yet identified.

Needless to say, if this study’s results stand up to further analysis and testing, the field of epigenetics (the study of inheritance controlled by something other than inherited genes) will be of even greater interest!