Generic bumps and recycled genetic cascades

How do you make a limb? Vertebrate limbs are classic models in organogenesis, and we know a fair bit about the molecular events involved. Limbs are induced at particular boundaries of axial Hox gene expression, and the first recognizable sign of their formation is the appearance of a thickened epithelial bump, the apical ectodermal ridge (AER). The AER is a signaling center that produces, in particular, a set of growth factors such as Fgf4 and Fgf8 that trigger the growth of the underlying tissue, causing the growing limb to protrude. In addition, there’s another signaling center that forms on the posterior side of the growing limb, and which secretes Sonic Hedgehog and defines the polarity of the limb—this center is called the Zone of Polarizing Activity, or ZPA. The activity of these two centers together define two axes of the limb, the proximo-distal and the anterior-posterior. There are other genes involved, of course—this is no simple process—but that’s a very short overview of what’s involved in the early stages of making arms and legs.

Now, gentlemen, examine your torso below the neck. You can probably count five protuberances emerging from it; my description above accounts for four of them. What about that fifth one? (Not to leave the ladies out, of course—you’ve also got the same fifth bump, it’s just not quite as obvious, and it’s usually much more tidily tucked away.)

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Folk genetics

Carel Brest van Kempen has extracted a few fascinating quotes from an old book he has. It’s titled Creative and Sexual Science, by a phrenologist and physiologist from 1870, and it contains some wonderful old examples of folk genetics.

President Bush would be pleased:

“Human and animal hybrids are denounced most terribly in the Bible; obviously because the mixing up of man with beast, or one beast species with another, deteriorates. Universal amalgamation would be disastrous.”

Although, unfortunately, he then goes on to use this as an argument against miscegenation.

Another lesson is that you shouldn’t deny pregnant women anything, or their longing will mark their child.

“A woman, some months before the birth of her child, longed for strawberries, which she could not obtain. Fearing that this might mark her child, and having heard that it would be marked where she then touched herself, she touched her hip. Before the child was born she predicted that it would have a mark resembling a strawberry, and be found on its hip, all of which proved to be true.”

Don’t let them see horrible things, either.

“Mrs. Lee, of London, Ont., saw Burly executed from her window; who, in swinging off, broke the rope, and fell with his face all black and blue from being choked. This horrid sight caused her to feel awfully; and her son, born three months afterwards, whenever anything occurs to excite his fears, becomes black and blue in the face, an instance of which the Author witnessed.”

And…uh-oh. Maybe George W. Bush won’t be so thrilled with this part.

“A child in Boston bears so striking a resemblance to a monkey, as to be observed by all. Its mother visited a menagerie while pregnant with it, when a monkey jumped on her shoulders.”

I think Carel needs to get busy and transcribe the whole thing onto the web. I know I’ll find these examples useful when I teach genetics this spring.

Maternal effect genes

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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.

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Clausen, Keck, Hiesey

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To continue a bit of theme, I mentioned that there were some different ways to approach biology, and that old-school systematists with their breadth of knowledge about the diversity of life are getting harder and harder to find. This is something I also bring up in my introductory biology course, where we discuss how biologists do their work, and I mention that one distinction you can find (which is really a continuum and frequently breached) is that there are bench scientists and field scientists, and they differ in multiple ways. Bench scientists tend to be strongly reductionist, tend to focus on one or very few species, and may study just one specific, highly inbred lab strain of a species, and try to minimize environmental variables. Variation is noise that interferes with getting at basic mechanisms. Field scientists, on the other hand, argue that the simplicity of the lab is unrealistic, that the proper study of organisms has to be done in the messy complexity of the real world, and think that variation, rather than being uninteresting noise, is fascinating stuff, the meat and potatoes of evolution. Both points of view have their place, and speaking for all biologists, I think we appreciate the power and necessity of both approaches. The money seems to mostly go to the bench guys, though, which does unfortunately skew the field as a whole.

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Pufferfish and ancestral genomes

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The fugu is a famous fish, at least as a Japanese sushi dish containing a potentially lethal neurotoxin that was featured on an episode of The Simpsons. Fugu is a member of the pufferfish group, which have another claim to fame: an extremely small genome, roughly a tenth the size of that of other vertebrates. The genome of several species of pufferfish is being sequenced, and the latest issue of Nature announces the completion of a draft sequence for the green spotted pufferfish, Tetraodon nigroviridis, a small freshwater species.

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Won for All

Last night, I had to read this book RPM mentioned. It’s not very long—about 100 pages, counting a preface, an epilogue, and an afterward, and it has lots of pictures—but be warned: it’s very inside baseball.

The book is Won for All: How the Drosophila Genome Was Sequenced(amzn/b&n/abe/pwll) by Michael Ashburner, and its subject is the rush to sequence the Drosophila genome in 1998-1999. It’s a rather strange twist on what I expected, though. While the subtitle says “How the Drosophila Genome Was Sequenced,” there is almost no science at all in the body of the book; instead, it’s all about the people and the politics, with Ashburner flitting about from place to place, yelling at people and eating sushi. It’s phenomenally entertaining.

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Modules and the promise of the evo-devo research program

Since Evolgen recognizes the importance of evo-devo, I’ll return the favor: bioinformatics is going to be critical to the evo-devo research program, which to date has emphasized the “devo” part with much work on model systems, but is going to put increasing demands on comparative molecular information from genomics and bioinformatics to fulfill the promise of the “evo” part. I’m sitting on a plane flying east, and to pass the time I’ve been reading a very nice review of the concept of modularity in evo-devo by Paula Mabee (also a fish developmental biologist, and also working in a small college in a small town in the midwest…but rather deservedly better known than yours truly). In addition to summarizing the importance of the concept of modularity to evolution and development, the paper also does something I always appreciate: it summarizes the key questions that the modern evo-devo research program is working to answer.

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A brief overview of Hox genes

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In previous articles about fly development, I’d gone from the maternal gradient to genes that are expressed in alternating stripes (pair-rule genes), and mentioned some genes (the segment polarity genes) that are expressed in every segment. The end result is the development of a segmented animal: one made up of a repeated series of morphological modules, all the same.

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Building an animal with repeated elements like that is a wonderfully versatile strategy for making an organism larger without making it too much more complicated, but it’s not the whole story. Just repeating the same bits over and over again is a way to make a generic wormlike thing—a tapeworm, for instance—but even tapeworms may need to specialize certain individual segments for specific functions. At its simplest, it may be necessary to modify one end for feeding, and the opposite end for mating. So now, in addition to staking out the tissues of the embryo as belonging to discrete segments, we also need a mechanism that says “build mouthparts here (and not everywhere)”, and “put genitalia here (not over there)”.

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