PZ Myers. 2004 May 24. Maternal Effect genes. <http://pharyngula.org/index/weblog/maternal_effect_genes/>. Accessed 2008 Dec 04.
Posted on M00o93H7pQ09L8X1t49cHY01Z5j4TT91fGfr on Monday, May 24, 2004
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.
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BTW our friend Rusty from the New Covenant has also been discussing genetics
http://newcovenant.blogspot.com/2004_05_01_newcovenant_archive.html#108514774475052360#: Posted by on 05/24 at 01:09 PM -
Just unleash the dogs on me DS!
A very informative post PZ. - Bleh. Amateur geneticists...the genome is not a spreadsheet, and that certain non-coding regions of the genome are conserved is not a matter of miracles or design.
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How widely distributed is bicoid? Has it been found in other insects? Non-insect arthropods? Other animal phyla?
I ask because it seems like exactly the sort of thing that would emerge early in animal evolution, and then get conserved.
Doug M. -
I'm going to get to that later, but no, actually bicoid is a bit weird and highly derived. Drosophila is highly derived, for that matter, and its development is not very well representative of what goes on in most other animals. Similar pieces are all there, but fruit flies have evolved to develop very, very rapidly, and there has been considerable streamlining of the process (I think) as well as the addition of features to make development more robust.
We vertebrates do use a relative of bicoid called goosecoid in our development -- it's a key player in defining our dorso-ventral axis. I'll also try to say more about that, later. -
Next time I meet someone who seems to have an arse
where their head should be I'm gonna call them a
son-of-a-bicoid!#: Posted by Jeremy Henty on 05/26 at 11:51 AM -
We vertebrates do use a relative of bicoid called goosecoid in our development -- it's a key player in defining our dorso-ventral axis.
So if you tinkered with goosecoid expression in, say, a primate, you could get something with two dorsal sides? In other words, a monkey with
no no no
...well, is there a general arthropod design for determining front-back (and top-bottom) in embryonic development? Pure curiosity, again -- please don't go out of your way.
Doug M. -
I haven't done it in a primate, but in zebrafish. See
Stachel, Scott E., D.J. Grunwald, and P.Z. Myers. (1993). Lithium perturbation and goosecoid expression identify a dorsal specification pathway in pre-gastrula zebrafish. Development 117(4):1261-1274.
Where you express goosecoid, you get additional dorsal structures, specifically notochords. You end up with embryos that look like a nest of snakes, with notochords radiating out everywhere.
We don't know the whole story yet, since most of the work has been done in Drosophila, but yes, there seem to be general molecular rules for how axes are determined. Dorsal in flies is determined by a gene called, sensibly enough, Dorsal, which, confusingly enough, has its effect in ventral tissues. Maybe I'll have to summarize that story sometime, too.