Give that fish a hand!

I have a bit of a peeve with a common analogy for the human genome: that it is the blueprint of the body, and that we can find a mapping of genes to details of our morphological organization. It’s annoying because even respectable institutions, like the National Human Genome Research Institute, use it as a shortcut in public relations material. And it is so wrong.

There is no blueprint, no map. That’s not how the system works. What you actually find in the genome are coding genes that produce proteins, coupled to regulatory elements that switch the coding genes off and on using a kind of sophisticated boolean logic. Each cell carries this complex collection of regulated genes independently and identically, but the boolean logic circuits produce different outputs varying with the inputs from the environment and the diverging histories of each cell. For instance, there is no code anywhere in the genome that commands the forelimbs to make five and only five digits: instead, a cascade of genes and cell movements produce a patterned tissue that in us contains sufficient mass and is of a size to generate five nuclei of condensing tissue that produce fingers.

It’s better to think in terms of cellular automata. The embryo is a pool of autonomous cellular robots that have general rules for how they should respond to environmental cues…and those cues tend to vary in predictable ways across the embryo, leading to a consistent cascade of action that produces a relatively consistent complex product, the multicellular organism.

The unfortunate consequence of those properties, though, is that you’ll never be able to look at a single gene from the genome and sort out what it does in the embryo. All the genes will be rather cryptic; you might be able to figure out that, for instance, the gene codes for an adhesion protein that makes the cell stick to a certain other class of cell, and that it’s switched on by gene products X and Y and turned off by gene product Z, but obviously you won’t be able to figure out its role until you figure out what activates genes X, Y, and Z, and whether the cell happens to be in a particular adhesive environment. And then when you look at X, Y, and Z, you discover that they have similar patterns of conditional logic in their expression.

In order to understand what a particular gene does, you have to understand what all the other genes do, as well as all the details of signaling and cell interactions that are going on, oh, and also, it’s entire developmental history, since epigenetic interactions can shape the future behavior of a cell lineage.

Hey, let’s all give up. This stuff is too hard.

No, let’s not. What it means is that you can’t derive the organism from the mere sequence of the genome — that is, the genomic information is not sufficient to comprehend morphology, because developmental processes add extra-genomic information to the generation of the organism. It means developmental biologists have job security (yay!), because the only way to decipher what is going on is to work backwards, from morphogenetic/physiological events to the underlying genes involved. This is not to imply that the genomic information is unimportant, only that understanding it requires complementing it with an understanding of cell:cell interactions, signaling, signal transduction, induction, and molecular patterning…all stuff that developmental biologists love.

Now if all you get from this is that the genome and organism are complex, interlocking, interdependent features that are so immensely and tightly integrated that evolution must be impossible, you aren’t thinking like a developmental biologist yet. Ask an evo-devo person about this stuff, and they’ll tell you that this is great…the way development works makes evolution of form easy.

That’s because there is no blueprint. What you have instead is a collection of flexible robots that have this property called plasticity: give them a novel environment or condition, and they don’t curl up and die and do nothing. Instead, they just follow the rules they’ve got and try to make something coherent out of whatever situation they find themselves in. They aren’t committed to making five fingers in any way; give them a reduced tissue mass, or an enlarged mass, or a variation in the signaling environment, and they’ll build something. And often it’s something surprising. Development is really, really good at producing emergent properties, precisely because it is autonomously rule-based rather than blueprinty.

All this buildup has a point: there’s an evolutionary issue that has a developmental resolution. It’s some really cool work on the development of the limb.

Page 1 of 3 | Next page