Maternal effect genes

Maternal effect genes are a special class of genes that have their effect in the reproductive organs of the mutant; they are interesting because the mutant organism may appear phenotypically normal, and it is the progeny that express detectable differences, and they do so whether the progeny have inherited the mutant gene or not. That sounds a little confusing, but it really isn't that complex. I'll explain it using one canonical example of a maternal effect gene, bicoid.

Bicoid is a gene that is essential for normal axis formation in the fly, Drosophila. It is this gene product that basically tells the fly embryo which end is the front end—the cartoon to the right illustrates what mutant larvae look like. The top picture is a normal, or wild type, Drosophila larva. Students of the fly will recognize that this animal is facing to the left by the presence of the dark mouthparts; fly experts will be familiar with the stippling in the figure, which illustrates characteristic locations of bristles on the animal's cuticle.

The picture below it is of an animal that lacks the bicoid gene product. It has no mouthparts, no head end at all; looking at the pattern of bristles, one can also see that the front end has the bristles found on the back end. (Yes, South Park fans, geneticists have created flies with two asses.)

The tricky part here is that that fly expressing the bicoid mutant phenotype may not carry the mutant gene. It could be genetically normal. What we know, though, from looking at it is that the poor two-assed fly's mother was a mutant. We know that because Drosophila embryos do not synthesize the bicoid gene product at all, not even the wildtype flies, and they all inherit it directly from Mom. The only way they could be lacking it is if their mother failed to pack it into the egg.

Here, for instance, is an in situ stain of a freshly laid wildtype Drosophila egg. An in situ stain is a way to dye specific RNA sequences, and in this case the egg is blue where ever bicoid RNA is present...and as can be seen, it is localized specifically to the front end of the egg. A photograph of a similarly stained egg from a bicoid mutant mother would look similar, except that there would be no blue spot at all—the egg would be a uniform gray. The key thing to understand is that that blue spot was not put there by the activity of the egg's genes, but exclusively by the action of the mother's genes. The diagram below illustrates how this pattern is set up during the formation of the egg in the mother fly's ovaries.

This is a follicle extracted from the ovary of a fly. It consists of several cell types, all of which will eventually be discarded except for one, the egg proper. The egg is going to grow to a relatively immense size, and it needs help to do that. An important contributor to that growth is a set of cells called nurse cells—the nurse cells are busy synthesizing essential proteins, such as yolk proteins, and stuffing them into the egg. They also make bicoid RNA (the blue stuff), which is similarly stuffed into the egg, along with other accessory proteins that make it sticky so that the bicoid RNA stays at that one end. There are also numerous cells called follicle cells that secrete the chorion, or shell that will surround the egg.

The diagram is only illustrating bicoid, but there are many RNAs and proteins that are being pumped into and secreted onto the surface of the developing egg. There are maternal genes that are necessary for the posterior end, and others that define dorsal and ventral sides, for instance.

Another important fact that isn't illustrated here is that the nurse and follicle cells are the mother's cells and have the mother's genotype. The egg, once it is fertilized and laid, is going to have a different genotype, and may actually acquire wildtype genes with wildtype bicoid...but it won't matter. If the maternal genes are defective, the damage is done before zygotic (from the fertilized egg) genes can do anything.

One clever experiment: the role of the bicoid gene product has been tested with what is called a rescue experiment, illustrated above. At left on the top is a bicoid⁺, or wildtype larva, and on the right is a bicoid^- larva that lacks any bicoid gene product. What if we injected it with bicoid? In the experiment, a little bit of bicoid⁺ cytoplasm is sucked out of the anterior end of a normal egg, and injected into the anterior end of an egg deficient for bicoid. That's enough to do a partial rescue; it's hard to get a perfect rescue, because dosage and localization are impossible to get exactly as they are in the intact egg.

The experiment at the bottom illustrates another interesting result: if the bicoid⁺ cytoplasm is injected into the middle of the egg, the embryo tries to form a head in the middle of it's body, as indicated by the difficult-to-see jumble of mouthparts that form there.

Maternal effect genes are common, and we know they are present in humans and other mammals—eggs contain many more informational macromolecules than just strands of DNA, and any organism above the level of a virus is going to pass information on to its progeny via the cytoplasm. However, maternal effect genes are most important in the very earliest stages of embryonic development, and defects in them are likely to be lethal. Maternal effect mutants in mammals aren't going to be seen as weird looking embryos, but as infertility problems, since embryos that fail in the first few days or weeks will simply be spontaneously aborted. There are few specifically identified maternal effect genes in mammals; one example is STELLA, identified in mice, in which homozygous carriers of the mutant allele look normal, but have severely reduced fertility.