Sad case out of India

i-55c6987e4f7e673a2ca2b05fa06cd344-wlimbs105b.jpg

What do you do when a child is born with ischiopagus?

  1. Sell her to the circus?

  2. Turn her into an object of religious veneration?

  3. Try surgery to correct the condition as much as possible?

This little girl born with six legs and two arms had the option of all three; she’s currently being operated on to remove four of the limbs. I don’t think it is an easy decision, except for the fact that her condition is messed up enough that she’s not likely to survive to adulthood without the surgery. On the complicating side, the operation costs £100,000, has substantial risk of death or paralysis, and will not restore full, normal morphology. Here’s a paper describing the long term outcome of another case of a separation of conjoined twins.

Because we can’t rewind the clock, developmental abnormalities often are not correctable—they are treatable, which is a whole different thing, but the doctors can’t change the fact that this child is the result of a scrambled developmental process.

I stand corrected. The two medial posterior limbs are arms, so this is a conjoined twin with four arms and four legs, and with the second twin headless.

Once more into the Haeckelian morass; or, Peter Moore is an illiterate fool

Perhaps you haven’t noticed, but we’ve got a serial spammer in the comments. This twit, calling himself Peter Moore (also known as Ken DeMyer, or Kdbuffalo, as he was known on Wikipedia before being banned there), is repeating himself over and over again, asking the same stupid question, never satisfied with any answer anyone gives him. Forty nine insipid comments in three days is enough.

I will answer him one last time. Any further attempt to spam multiple comment threads with his demands (and this alone makes him an ass: an incompetent, unqualified hack like Moore is in no position to make demands) will result in his immediate banning.

[Read more…]

Nobel in Medicine goes to…

I’ve known for years that this was going to happen: Mario Capecchi, Oliver Smithies and Briton Martin Evans have won the Nobel Prize in Medicine for their work on targeted gene mutations. If you’re interested in what kinds of work they’ve done, I described one paper on Hox regulatory evolution, and this work on the evolution of the Hox code wouldn’t have been possible without their knockout techniques.

Evo-devo of mammalian molars

Blogging on Peer-Reviewed Research

I’ve written a long introduction to the work I’m about to describe, but here’s the short summary: the parts of organisms are interlinked by what has historically been called laws of correlation, which are basically sets of rules that define the relationship between different characters. An individual attribute is not independent of all others: vary one feature, and as Darwin said, “other modifications, often of the most unexpected nature, will ensue”.

Now here’s a beautiful example: the regulation of the growth of mammalian molars. Teeth have long been a useful tool in systematics—especially in mammals, they are diverse, they have important functional roles, and they preserve well. They also show distinct morphological patterns, with incisors, canines, premolars, and molars arranged along the jaw, and species-specific variations within each of those tooth types. Here, for example, is the lower jaw of a fox. Look at the different kinds of teeth, and in particular, look at the differences within just the molars.

i-a5e17fbf862bbaf85cb8caf7d8e447d1-fox_jaw.gif
This example — the lower teeth of a grey fox — shows the three-molar dental phenotype typical of placentals.

Note that in this animal, there are three molars (the usual number for most mammals, although there are exceptions), and that the frontmost molar, M1, is the largest, M2 is the second largest, and M3, the backmost molar, is the smallest. This won’t always be the case! Some mammals have a larger M3, and others may have three molars of roughly equal size. What rules regulate the relative size of the various molars, and are there any consistent rules that operate across different species?

To answer those questions, we need to look at how the molars develop, which is exactly what Kavanagh et al. have done.

[Read more…]

Laws of correlation and the derivation of evolutionary patterns from developmental rules

Cuvier, and his British counterpart, Richard Owen, had an argument against evolution that you don’t hear very often anymore. Cuvier called it the laws of correlation, and it was the idea that organisms were fixed and integrated wholes in which every character had a predetermined value set by all the other characters present.

In a word, the form of the tooth involves that of the condyle; that of the shoulder-blade; that of the claws: just as the equation of a curve involves all its properties. And just as by taking each property separately, and making it the base of a separate equation, we should obtain both the ordinary equation and all other properties whatsoever which it possesses; so, in the same way, the claw, the scapula, the condyle, the femur, and all the other bones taken separately, will give the tooth, or one another; and by commencing with any one, he who had a rational conception of the laws of the organic economy, could reconstruct the whole animal.

Cuvier famously (and incorrectly) argued that he could derive the whole of the form of an animal from a single part, and that this unity of form meant that species were necessarily fixed. An organism was like a complex, multi-part equation that used only a single variable: you plugged a parameter like ‘ocelot’ into the Great Formula, and all the parts and pieces emerged without fail; plug in a different parameter, say ‘elephant’, and all the attributes of an elephant would be expressed. By looking at one element, such as the foot, you could determine whether you were looking at an elephant or an ocelot, and thereby derive the rest of the animal.

[Read more…]

Tandem repeats and morphological variation

Blogging on Peer-Reviewed Research
i-ccbc028bf567ec6e49f3b515a2c4c149-old_pharyngula.gif

All of us mammals have pretty much the same set of genes, yet obviously there have to be some significant differences to differentiate a man from a mouse. What we currently think is a major source of morphological diversity is in the cis regulatory regions; that is, stretches of DNA outside the actual coding region of the gene that are responsible for switching the gene on and off. We might all have hair, but where we differ is when and where mice and men grow it on their bodies, and that is under the control of these regulatory elements.

A new paper by Fondon and Garner suggests that there is another source of variation between individuals: tandem repeats. Tandem repeats are short lengths of DNA that are repeated multiple times within a gene, anywhere from a handful of copies to more than a hundred. They are also called VNTRs, or variable number tandem repeats, because different individuals within a population may have different numbers of repeats. These VNTRs are relatively easy to detect with molecular tools, and we know that populations (humans included) may carry a large reservoir of different numbers of repeats, but what exactly the differences do has never been clear. One person might carry 3 tandem repeats in a particular gene, while her neighbor might bear 15, with no obvious differences between them that can be traced to that particular gene. So the question is what, if anything, does having a different number of tandem repeats do to an organism?

[Read more…]

Basics: Master Control Genes and Pax-6

Blogging on Peer-Reviewed Research

One concept that is sometimes used in developmental biology is the idea of the “master control gene” or “master switch” — a single gene whose expression is both necessary and sufficient to trigger activation of many other genes in a coordinated fashion, leading to the development of a specific tissue or organ. It’s a handy concept on which to hang a discussion of transcription factors, but it may actually be of rather limited utility in the real world of molecular genetics: there don’t seem to be a lot of examples of master control genes out there! Pax-6 is the obvious one, a gene that initiates development of the eye, and other genes may be mentioned in certain stem cell pathways, but even in the eyes of vertebrates, for example, eye development is more complicated than a single switch, and similarly, many other developmental processes seem to use multiple or redundant regulatory controls — the cases where we have a single gene bottleneck are either rare or poorly represented in the literature.

They’re still at least pedagogically useful, though — it’s a simple case of imposition of a specific developmental pathway on a patch of tissue.

[Read more…]

The Hox code

Blogging on Peer-Reviewed Research

The Hox genes are a set of transcription factors that exhibit an unusual property: they provide a glimpse of one way that gene expression is translated into metazoan morphology. For the most part, the genome seems to be a welter of various genes scattered about almost randomly, with no order present in their arrangement on a chromosome — the order only becomes apparent in their expression through the process of development. The Hox genes, on the other hand, seem like an island of comprehensible structure. These are all genes that specify segment identity — whether a segment of the embryo should form part of the head, thorax, or abdomen, for instance — and they’re all clustered together in one (usually) tidy spot.

Within that cluster, we see further evidence of order. Look at just the Drosophila part of the diagram below: there are 8 Hox genes in a row, and their order within that row reflects the order of expression in the fly body. On the left or 3′ end of the DNA strand, lab (labial) is expressed in the head, while Abd-B (Abdominal-B) is expressed at the end of the abdomen.

i-3d10d2b119aa766df39871ead4a8a19c-hoxcode_hox.gif
Schematic of relationship between Drosophila and mouse Hox genes. Hox genes are shown as colored boxes in their order on the chromosome. Orthologous genes between Drosophila and mouse, and paralogous mouse genes are shown color-coded.

Knocking out individual Hox genes in the fly causes homeotic transformations — one body part develops into another. These genes are early actors in the cascade of interactions that enable the development of morphologically distinct regions in a segmented animal — the activation of a Hox gene from the 3′ end is one of the earliest triggers that leads the segment to develop into part of the head.

Now look at the mouse part of the diagram above. We vertebrates have Hox genes that are homologous to the fly Hox genes, and they’re also clustered in discrete locations with 3’→5′ order reflecting anterior→posterior order of expression. There are differences — the two most obvious that we have more Hox genes on the 5′ side (these correspond to expression in the tail—flies do not have anything homologous to the chordate tail), and vertebrates also have four banks of Hox genes, HoxA, HoxB, HoxC, and HoxD. This complicates matters. Vertebrates have these parallel, overlapping sets of Hox genes, which suggests that morphology could be a product of a combinatorial expression of the genes in the four Hox clusters: there could be a Hox code, where identity can be defined with more gradations by mixing up the bounds of expression of each of the genes.

[Read more…]

FunGenEvoDevo

I got some email today with lots of constructive suggestions (See? Not all my email is evil!) for how we ought to change the education of biology students — such as by giving them a foundation in the history and philosophy of our science, using creationist arguments as bad examples so the students can see the errors for themselves, etc. — and it was absolutely brilliant, even the parts where he disagreed with some things I’d written before. Best email ever!

Of course, what helped is that I spent my summer “vacation” putting together a new freshman first semester course for biology majors that I’m teaching for the first time right now, and it’s exactly the course he described. It was eerie, like one of my future students had invented a time machine and come back into the past to tell me what to do. A lot of the course content is locked up behind a password-protected firewall, I’m afraid, but just to show you what I’m talking about, I’ll put the course schedule below the fold.

[Read more…]