Books : reviews

Sean B. Carroll.
Endless Forms Most Beautiful: the new science of evo devo and the making of the animal kingdom.
Weidenfeld & Nicolson. 2005

rating : 2 : great stuff
review : 25 March 2008

This is an excellent account of the "new science" of evolutionary development (EvoDevo), explaining how animals have the forms and structures that they do, as a consequence of genetics, the developmental process from embryo to adult, and how all this has evolved. It provides a foundational plank of evolutionary theory. (The title is a quotation from the final sentence of Darwin's The Origin of Species.) The previous 1940s so-called "Modern Synthesis" of evolutionary theory misses out this key step of development: how a single cell grows, divides, differentiates and structures into an adult organism. Understanding this development also gives key insights into how evolution works.

In 300 clearly-argued and beautifully written pages, Carroll covers four areas:

[p134] four critical ideas about animal development---the modularity of animal architecture, the genetic tool kit for building animals, the geography of the embryo, and the genetic switches that determine the coordinates of tool kit gene action in the embryo.

The first thing to understand is that the typical "Ladybird book" model of genetics -- one gene codes for one protein, and proteins build the organism -- is severely lacking. It misses out the key fact of gene regulation:

[p12] only a tiny fraction of our DNA, just about 1.5 percent, codes for roughly 25,000 proteins in our bodies. ... Around 3 percent of it ... is regulatory.

That is, there is about twice as much regulatory DNA as coding DNA. Genes can be selectively switched on or off in different parts of the organism, and the regulation structure is a complex dynamic network itself mediated by genes and proteins. Many of the proteins expressed act in this network to control the expression of other proteins, rather than directly form building blocks of the organism's body.

[p112] In animals, genetic switches are a bit more elaborate [than in bacteria]. Generally, individual switches in animals are longer sequences of DNA, and they are bound by a larger number and greater variety of proteins. Some of these proteins activate transcription, some repress it. It is by "computing" the inputs of multiple proteins that switches transform complex sets of inputs into the simpler outputs we see as ... patterns of gene expression ... . Importantly, one gene may be regulated by many separate switches such that the gene is used many times and in different places ...
[p118] An average-size switch is usually several hundred base pairs of DNA long. Within this span there may be anywhere from half a dozen to twenty or more signature sequences for several different proteins.
[p116] the throwing of every switch is set up by preceding events, and ... a switch, by turning on its genes in a new pattern, in turn sets up the next set of patterns and events in development.

Carroll doesn't say much about timescales, but it is clear from this passage that they must be important. Information is flowing through the system, (diffusion, oscillatory dynamics, etc), which is simultaneously growing. Not only changing these switches, but changing timescales (eg oscillation frequencies, growth rates) so that the information arrives sooner or later, would seem to be important.

One key point is that the same gene, expressed in different places, can have multiple different consequences. The Distal-less gene affects the growth of distal structures (legs and wings), but when expressed within a butterfly wing, also controls the formation of "eyespots" there. This trick is seen again and again: there are a few "tool kit" genes that do their stuff, but the details of what they actually do depends on where they are expressed, and that expression is affected by the regulatory network. (One thing that I don't think is made completely clear is how the genes know where they are in the embryo or developing animal: it appears from some of the discussion as if they might have some "absolute" location information, rather like latitude and longitude, but it isn't clear where that information comes from.)

Amazingly, the tool kit genes have been preserved virtually unchanged over many million years of evolutionary history (creatures as diverse as arthropods and vertebrates have many homologous tool kit genes): what has evolved is mainly the switching network. The motto is: keep the parts constant, evolve the processes by which they are combined.

Animals have a second trick: they use repetition (segmentation) to build multiple uniform structures (segments), then use different switchings to specialise individual segments in a different way.

[p33, on Williston's law] The trend appears to be that once expanded in number, serial homologs became specialized in function and reduced in number.
[p157] The increase in the number of different appendage and segment types in arthropod evolution is the produce of generating a greater number of unique zones in the embryo in which specific or combinations of Hox genes are expressed.
[p169] The importance of serially repetitive body design is the ability to shift the burden of some task from two or more pairs of structures onto fewer structures, then to specialize the freed-up structures for new purposes. This has served the vertebrates well, but the arthropods have absolutely run riot with the idea.

This segmentation and specialisation allows evolution to work on parts of the body at a time: for example, various distal structures like mandibles, legs, wings, spinnerets, whatever, can evolve somewhat independently of each other. (In fact, the discussions of the amazing variety of body parts that "legs" have evolved into in different creatures is, well ... amazing!)

[p131] Because individual switches are independent information-processing units, evolutionary changes in one switch of a tool kit gene or in a switch controlled by a tool kit protein can alter the development of one structure or pattern without altering other structures or patterns.

Thus the EvoDevo insight get round the "hopeful monster" problem of evolution: how a mutation can produce a different and more successful organism. That is, evolve control rather than components, in a modular structure. It also provides further ammunition (should it be needed) against anti-evolutionists. No-one (surely?) can deny that development occurs: the growth of a complete and complex organism from a single cell over a lifetime -- which lends credence to the evolution of complexity over the much longer evolutionary timescales.

And this link between evolution and development -- that evolution can proceed by exploiting developmental processes -- provides further understanding of how evolution actually works to produce novel complex structures. Evolution is a tinkerer that plays around with the tool kit it has got. A great example is duck feet. In the embryo, hands and feet are initially disc-like, and there is a gene that makes the skin between fingers and toes die off. In a duck's webbed feet, this gene is inhibited. In other words, the skin doesn't die away because the command that tells it to die away is stopped from occurring. Evolution doesn't remove the unnecessary gene (in the way that an intelligent programmer might remove unused code), it just blocks its expression.

There is a welcome cautionary note, hidden in the bibliography, against over-interpretation of overly-simplistic models. Just because a computational model replicates patterns seen in reality doesn't mean it employs the same mechanism as reality:

[p318] the central importance of genetic switches to pattern formation has not yet fully penetrated the computational modeling world ... The continuing mistake is being seduced into believing that simple rules that can generate patterns on a computer screen are the rules that generate patterns in biology.

There is much more than this brief summary can encompass. This is an excellent book, and should be read by everyone with an interest in evolution.

Sean B. Carroll.
The Making of the Fittest: DNA and the ultimate forensic record of evolution.
Quercus. 2006

Sean B. Carroll.
The Serengeti Rules: the quest to discover how life works and why it matters.
Princeton University Press. 2016

How does life work? How does nature produce the right numbers of zebras and lions on the African savanna, or fish in the ocean? How do our bodies produce the right numbers of cells in our organs and bloodstream? In The Serengeti Rules, award-winning biologist and author Sean Carroll tells the stories of the pioneering scientists who sought the answers to such simple yet profoundly important questions, and shows how their discoveries matter for our health and the health of the planet we depend upon.

One of the most important revelations about the natural world is that everything is regulated—there are rules that regulate the amount of every molecule in our bodies and rules that govern the numbers of every animal and plant in the wild. And the most surprising revelation about the rules that regulate life at such different scales is that they are remarkably similar—there is a common underlying logic of life. Carroll recounts how our deep knowledge of the rules and logic of the human body has spurred the advent of revolutionary life-saving medicines, and makes the compelling case that it is now time to use the Serengeti Rules to heal our ailing planet.

A bold and inspiring synthesis by one of our most accomplished biologists and gifted storytellers, The Serengeti Rules is the first book to illuminate how life works at vastly different scales. Read it and you will never look at the world the same way again.