Endless Forms Most Beautiful

Sean Carroll, W.W. Norton, 2005

Preface: Revolution #3

ix Calls the first two revolutions in biology evolution and genetics, or natural selection and DNA.

x "Neither natural selection nor DNA directly explains how individual forms are made or how they evolved."

x "Evo-Devo" is the third revolution, the insights from developmental biology and evolutionary developmental biology.

Introduction: Butterflys, Zebras and Embryos

p2 Interesting discussion about how Darwin was profoundly influenced by Alexander von Humbolt's "Personal Narrative", the story of his travel around South America. Also highlights Alfred Russel Wallace and Henry Walter Bates and extols their influence on the first revolution of biology. Discusses the great variety of living forms.

p5 Quotes Thomas Huxley here and on p7 to point to the marvel of development from the embryo, but also to bring in the philosophical position of Huxley "evolution excludes creation and all other kinds of supernatural intervention".

1. Animal Architecture: Modern Forms, Ancient Designs

p33 Williston's Law: Williston declared in 1914 "it is a law in evolution that the parts in an organism tend toward reduction in number, with the fewer parts greatly specialized in function."

2. Monsters, Mutants and Master Genes

p40 Thalidomide and other "teratogens"

p41 Concept of the "organizer" - Nobel laureate Spemann

p42 a limb bud multiplies by more than 1000 - orderly formation determined by the organizer. Tissue from "zone of polarizing activity", when translated elsewhere, can grow a whole structure - Saunders

p43 Organizer of butterfly wingspan - Nijhout

p45 Search for the "morphogens" responsible for the action of the organizers.

p46 Argues strongly against the "hopeful monster" paradigm.

p50 "Frankenflies" - legs instead of antennae on fruitfly illustrate "homeotic" genes - master genes.

3. From E. coli to Elephants

p53 "What is true for E. coli is also true for the elephant." This quote by Jacques Monod, Nobel Laureate, was quite daring at the time it was made, but Carroll points out the developments that support it. He gives interesting biographical details about Monod, Jacob and Lwoff, the sharers in the Nobel Prize, who were all active in World War II.

p54 Brief overview of proteins

p56 About Jacob & Monod's 1965 Nobel Prize work on "enzyme induction".

p57-58 Brief overview of transcription and translation

p59 E Coli lactose repressor discussion with diagram. The presence of lactose knocks off the repressor and allows the gene for producing the enzyme for metabolizing lactose to be active, a classic gene switch. "The control of enzyme production by the lac repressor is the classic example of gene logic."

p60 Features of gene logic:

  1. the regulated use of a gene occurs through the on/off binding of a DNA binding protein
  2. the DNA binding protein recognizes a specific DNA sequence near a gene.

He points to this as the key to cell differentiation.

p61 Homeobox
The fruit fly has just 4 chromosomes. 8 homeostatic genes referred to as Hox genes. 180 base pairs corresponding to 60 amino acid section common to all 8 homeotic genes dubbed the homeobox - Hox refers to the homeotic genes with these homeoboxes.

p63 Homeotic proteins might regulate genetic switches in animal development, so that's why they affect the formation and identity of whole structures.

p64 McGinnis & Levine cited. Homeoboxes in many species. Mice and frog homeo domain identical in 59 of 60 locations. Flies and mice have similar features even though they diverged 500 million years ago.

p65 Homeobox compared to Rosetta stone.

p65 Hox genes in mice in clusters as in fruit fly, similar in embryo. "Clusters of Hox genes shaped the development of animals as different as flies and mice.." "Disparate animals were built using not just the same kind of tools, but indeed, the very same genes."

p67 Pax-6 gene and eye development - transplant mouse Pax-6 into fly and develop fly eye features.

p69 Dll gene for appendages in many types of animals

p70 about two dozen families of homeodomains

p73 Nusslein-Volhard & Wieshaus Nobel 1995 for mapping genes of fruit fly -"paved the way for evo-devo". See also p255 in Darwin's Doubt for more about them.

p74 "all members of the toolkit shape development by affecting how other genes are turned on or off in the course of development" Parts of toolkit include transcription factors, signaling pathways ..

p75 Diagram of tookkit

p79 "..mice and humans have nearly identical sets of 25,000 genes and that humans and chimps are almost 99% identical at the DNA level."

4. Making Babies: 25,000 Genes, Some Assembly Required

Good developmental overview of research on segmenting from embryos and the work of the toolkit in producing form.

5. The Dark Matter of the Genome: Operating Instructions for the Toolkit

With analogy to the universe's dark matter, the majority of the DNA which is not part of the protein blueprints includes the genetic switches. I thought he was going to make the case that the so-called junk-DNA was not junk, so was surprised to find:

p112 "Most dark matter contains no instructions and is just space-filling 'junk' accumulated over the course of evolution. In humans only about 2-3% of our dark matter contains genetic switches that control how genes are used." Maybe he hasn't seen the ENCODE project results >80% functional.

p112 Recaps lactose and lac repressor story from Ch 3 and says "In animals, genetic switches are a bit more elaborate .. longer sequences of DNA .. bound by larger number and greater variety of proteins" He introduces a "computing" metaphor.

p113 "one gene may be regulated by many separate switches such that the gene is used many times and in different places.."

p118 Example of combinatorial logic.

6. The Big Bang of Animal Evolution

p134 Summarizes the early part of the book as illustrating "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."

p134 Points forward to the central idea of the second half of the book: "the central idea is that animal forms evolve through changes in embryo geography."

p135 "discoveries have revealed one of the "Holy Grails" of evolutionary biology - the precise genetic changes responsible for evolution in particular species."

p142 Chart of Deuterostomes and Protostomes, the two main groups of bilateral animals.

p145 Overview of Cambrian explosion

p151 Chart and argument that arthropods and lobopodians had at least 10 Hox genes.


p152 After having done a general overview of the Cambrian explosion and the types of fossils found, he tells an interesting story of the analysis of the DNA of a living animal in Australia, an onychophoran. It is a small brown caterpillar-like animal with primitive leg-like structures called lobopods like several of the Cambrian fossils. Since there are many living arthropods, if they could show commonality of any genetic features of onychophorans and arthropods, they could reasonably imply that they were features of their common ancestor and thus project back one step before the Cambrian explosion. They found that they had all of the Hox genes in common.

p155 Diagram to show how the shifting zones of Hox gene expression shape the differences in arthropod design.

p158 Diagram of supposed role of Hox cluster duplication in the development of vertebrates.

p164 "last common ancestor [before the Cambrian explosion] was fairly complex -- full genetic toolkit was in place --potential of the tool kit was realized largely through the evolution of switches and gene networks and the shifting of Hox zones"

p164 "Cambrian explosion was an ecological phenomenon"

7. Little Bangs: Wings and other Revolutionary Inventions

p175 Gills to wings. Distal-less limb building gene

p177 Illustration nymph gills to adult wings (apterous and nubbin proteins) New example of Williston's Law

p178 Separation of nymph and adult stages in one genome

p178-179 Repression of Hox proteins in all but 2nd and 3rd thoracic segments - a switching operation

p179 Spiders on land in same branch as horseshoe crabs. Structures - lungs and spinnerets - express apterous and nubbin, tracheal tubes

p181 Illustration - gills - ?

p182 Example spider Hox genes lungs 7, tracheal tubes 7,8 spinnarets 7,8,9. Related to geography of embryo. Rear wing different.

p183 Extra Hox protein expressed in rear wing, illustration of Ubx hox

p184 Fish fingers to bat wings

p185 Discusses late Devonian 362-375 My

p186 Illustration of fish fingers

p186 Five digits for 300 million years.

p189 Wing illustration, pterodactyl (fingerwings), bird (arm wings), bat (hand wings)

p192-193 Stickelback fish as model example of evolutionary change

p194 Four secrets of evolutionary innovation

  1. Work with what is present
  2. Multifunctionality
  3. Redundancy
  4. Modularity

p195 Switches are the secret to modularity. Underlying modularity is modular embryonic geography.

8. How the Butterfly Got Its Spots

p197 Henry Walter Bates and years in the Amazon, great friend of Darwin.

p199 Illustration of Batesian mimicry

p201 Fred Nijhout and butterfly wing patterns

p204 Butterfly scales - single cell - mod bristles - scales escape spider webs - scale microanatomy

p207 Butterfly 5 larval stages, "organizer" for eye spot.

p207 "Since insect wings evolved only once, then what we knew about the making of fruit fly wings should apply, in general, to the making of butterfly wings. Our hope was, if we were lucky, that studying the butterfly counterparts of the fruit fly tool kit might lead us to clues about the unique features of butterfly wings. We were lucky."

p208 They looked at the tiny wing discs on the caterpillar which corresponded to the future wings. Found that there was a common geography for the development of insect wings. Described it as the "Distal-less" gene learning a new mechanism. Illustration p209 shows an added genetic switch associated with the gene in the butterfly compared to the fly.

p210 Great color plates of butterfly wing spots. They discovered two more genes called "Spalt" and "Engrailed" that were involved in producing a spot and a ring on the butterfly wing. Shows pattern on caterpillar wing disc and on butterfly wing.

p211 In a section titled "My Fifteen Minutes" he relates call from NY Times relative to Science article, then TV, then award by Time magazine in Washington, then call from Hollywood producer.

9. Paint It Black

p231 After discussion of melanism in animals, shows diagram of MC1R receptor protein, which is involved in melanism in a number of animals. Shows the places were alteration of MC1R can lead to a black version of the species. The stimulating and inhibiting hormones have been established. The Agouti protein is the inhibitor. He comments that the reason this protein process can evolve is that it affects pigmentation and little or nothing else, so nothing significant is wrecked if it changes by mutation.

p233 MC1R responsible for dark and light mice on dark and light rocks, so natural selection has been able to work to separate those populations, and it is easy to see that this sort of evidence would build confidence in the action of natural selection. Another population of light and dark mice a few hundred miles away do not use MC1R, but also separate into light and dark, apparently by natural selection.

p236 Kermode or spirit bear of Pacific Northwest has a MC1R mutation that knocks out the function of the receptor, and no melanin is made. In humans MC1R is responsible for red hair, freckling, light pigmentation and sun sensitivity.

p237 White or light underside and darker top fur identified with Agouti inhibiting action on the underside.

p237-242 Reflection on whether the zebra is white with black stripes or black with white stripes.

p242-3 Comments on spots.

p246 Returns to zebras to make the natural selection argument that stripes matter for zebras - evidence: zebras have stripes.

10. A Beautiful Mind: The Making of Homo Sapiens

p250 Erich Fromm "Man is the only animal for whom his own existence is a problem he has to solve."

A history of the development of man by evolution through the hominids. Covers the story in a textbook fashion, but with the clear intent to picture man's development as no different from that of other animals, and in the process to diminish man's significance.

p268 The 98.8% paradox and the making of Homo Sapiens

p269 "In fact, 96% of all genes in the human are found in the exact same relative order in human chromosomes as in the mouse chromosomes. This is a remarkable degree of similarity. These figures tell us that in the course of 75 million years of mammalian evolution, and at least 55 million years of primate evolution, our genome and that of a rodent contain essentially the same genes in mostly the same organization. Differences in gene number and organization have not played much, if any, role in the origin of humans or primates."

p271 "In a classic study three decades ago, Mary Claire King and Allan Wilson showed that the sequences of chimp and human proteins were nearly identical and drew the conclusion that evolutionary differences were due to changes in gene regulation." "The weight of evidence from Evo Devo and comparative genomics tells us that these earlier deductions were on the right track."

p271 Evolution of human jaw muscles as an example

p274 The FOXP2 gene and human speech.

11 Endless Forms Most Beautiful

p285 "The first and still perhaps the most stunning discovery of Evo Devo is the ancient origin of the genes for building all sorts of animals. .. The fact that such different forms of animals are shaped by very similar sets of tool kit proteins was entirely unanticipated."

p285 "The shared generic tool kit for development reveals deep connections between animal groups that were not at all appreciated from their dramatically different morphologies."

p285 "the discovery that organs and structures that were long viewed as independent analogous inventions of different animals, such as eyes, hearts, and limbs, have common genetic ingredients controlling their formation has forced a complete change in our picture of how complex structures arise. Rather than being invented repeatedly from scratch, each eye, limb, or heart has evolved by modification of some ancient regulatory networks under the command of the same master gene or genes."

p287 About the development of structures: "The success of these groups has been enabled by the flexibility of the systems governing Hox gene deployment such that individual structures can evolve independently of others." This language "systems governing Hox gene deployment" seems to evoke epigenetic systems that are not spelled out here. He refers to "regulatory inputs and switches" in the next paragraph.

p288 "The key to innovation at the genetic level is the multifunctionality of tool kit genes. The multifunctionality of tool kit genes stems from their deployment at different times and places through batteries of genetic switches. In this manner, a protein such as Distal-less can act at one time to promote limb formation, and at another to promote eyespot development. The protein made each time is identical, so the difference in function is due to its action on different switches in these different contexts."

p289 Francois Jacob "Nature works as a tinkerer with available materials, not as an engineer does by design."

p290 Cites Jacques Monod and "Chance and Necessity" as quoting the greek philosopher Democritus who said "Everything existing in the Universe is the fruit of chance and necessity."

p291 Section on microevolution and macroevolution

p291 "The preservation of Hox genes and other tool kit genes for more than 500 million years illustrates that the pressure to maintain these proteins has generally been as great as that upon any class of molecules.""The continuity of the tool kit and the continuity of structures throughout this vast time illustrate that we need not invoke very rare or special mechanisms to explain large-scale change. "Evo-Devo reveals that macroevolution is the product of microevolution writ large."

p296 Section on evolution and creation

p297 "in 1996, Pope John Paul II reiterated the Catholic position that the human body has evolved according to natural processes. Furthermore, he noted that the evidence for evolution had increased greatly, to the point where it is 'more than a hypothesis'." "My ordained teachers at St Francis de Sales High School in Toledo introduced me to Darwin and evolution."

p298 Commentary on Behe and Darwin's Black Box. Having introduced the 'God of the gaps' charge, he criticized Behe: "One example of a mistaken faith in those gaps is that of biochemist Michael Behe, who in 1996 published Darwin's Black Box: The Biochemical Challenge to Evolution. Written by a credentialed scientist, Behe's book was received as a godsend by creationists. But Behe's main claim, that the living cell is an entity of irreducible complexity, is empty. Behe was counting on biology to hit a wall in reducing complex phenomena to molecular processes. He joins a long line of prognosticators whose pessimistic forecasts have been obliterated in the continuing revolution in the live sciences."

p300 Understandably, Behe hit a nerve with his skepticism about the all-sufficiency of Darwinian evolution. So he pursues that understandable resentment with a few quotes and revealing personal involvement with lines like "As exasperating as the continuous battle with creationists may seem .." And some outrageous theology from John Haught "..we need to recast all of theology in evolutionary terms."

p301 Interesting section "Endless Forms Most Endangered" where he talks about human role in animal extinction.

p330 Einstein quote "A hundred times every day I remind myself that my inner and outer life are based on the labors of other men, living and dead, and that I must exert myself in order to give in the same measure as I have received and am still receiving." from "The World As I See It", Ideas and Opinions (1954) trans Sonja Bargmann.

General reflections on the book. Carroll does a wonderful job of describing the Hox genes as a master toolkit for the developing embryo, and describes his view of the great degree of commonality of this toolkit for all of life. He does a great job of communicating the excitement of the research, the work with graduate students and the excitement of new discovery. His viewpoint seems to be that the existence of this toolkit along with straight neo-Darwinian mutation/selection/survival of the fittest is sufficient to explain the emergence of complexity. There is where I begin to diverge from him. He doesn't deal significantly with abiogenesis, it realistically being outside the scope of his intent for this book. But the kinds of questions that remain unanswered in the origin of life remain unanswered in my mind in the development of new body plans, even given the powerful Hox gene toolkit. There is an enormous amount of complex specified information and major coordinated systems in the jump to a new body plan, and I can't see that Hox genes by themselves can do it. He talks about gene switches and the adding of gene switches to a Hox gene like distal-less to create a butterfly wing spot, but there is an intimation of "agency" there. And the whole epigenetic framework of a cell contains many coordinated systems, and my feeling is that the implementation of a new "switch" added to a Hox gene involves a whole coordinated system. He would probably be offended by the parallel, but it almost seems like there is a "black box" of epigenetic coordination that is hanging in mid air around his wonderful treatment of the Hox genes.

Windows of Creation
Evidence from nature Is the universe designed?
Reading Reference
  Reasonable Faith Go Back