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TEACHING EVOLUTION THROUGH DEVELOPMENT
Talk delivered at the 61st Annual Meeting of the Society for Developmental
Biology, Madison, Wisconsin, July 21, 2001
This version includes footnotes concerning Creationism.
The PowerPoint presentation accompanying this talk is available online
from this same site
Scott F. Gilbert
Professor of Biology
Swarthmore College
Swarthmore, PA 19081 USA
I. Introduction
Development and education share many features. Indeed, the German words for
development--Entwicklung and Bildung--can also mean education. We talk about
the cell fates being instructed, and many of our educational theories are based
on competence and reception. Education is but epigenesis writ very large.
So I am especially appreciative of speaking here today about the role that
developmental biology can play in education, especially educating our
undergraduates and high school students about evolution. I will contend that we
can teach evolution more effectively using developmental genetics than
population genetics. Both are required for any theory of evolution, but I propose
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that students will learn the principles of evolution better from examples of animal
development than they can from the mathematics of natural and laboratory
populations. The examples I will use are perhaps not the ones others would use.
I will be using examples that my undergraduates would appreciate--which means
I will mainly be talking about vertebrates and insects. My apologies in advance to
the allies of all other clades.
I also will be discussing evolutionary developmental biology historically, since
this is a special year. It has been 25 years since the conception-- (not the birth)-of evolutionary developmental biology. In 1977, three publications enabled the
work of evolutionary developmental biology ("evo-devo") to begin. These
publications are
1. Stephen J. Gould's Ontogeny and Phylogeny
2. Francois Jacob's "Evolution and tinkering," Science 196: 1161-1166.
3. A. Maxam and W. Gilbert , "A new method for sequencing DNA." Proc. Natl.
Acad. Sci. U S A. 74: 560-4.
I think that these papers were the factors that permitted the development and
birth of evo-devo.
II. Introducing evolution
Now, when we introduce evolution to our students, we usually
concentrate on natural selection, the mechanism of Darwinian evolution. This is
important.
SLIDE 1. The main tenets of Darwinian natural selection
So we show that variation exists within a species.
SLIDE 2: Variation amongst undergraduates
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We show that most animals die before reproducing.
SLIDE 3. Reproductive rates without death.
Without death, two houseflies would have 2 X 1020 houseflies
between May and October.
We show that the mortality can be selective.
SLIDE 4. Changes in Galapagos finch beak size (after Grant, 1986.)
Here we see data from the Grants on the Galapagos finches whose beak
changed due to the drought of 1976/1977, where birds with larger beaks
survived preferentially. The larger beaks enabled their possessors a wider range
of plant seeds on which to feed.
And we show that the progeny resulting from such selection are more fit for their
environment, having inherited the genes that made their parents fit.
SLIDE 5. Changes in genes due to selection with pesticides
The mosquitoes that are resistant to DDT have evolved multiple copies of the
esterase genes that enable them to detoxify it; the cotton budworm has altered
the target of the poison, and houseflies have altered the proteins that transport
the poison. The insecticides select for those resistant phenotypes, and the genes
that confer this resistance are transmitted to the next generation.
Having established that evolution happens, we can then show how evolution
can be explained genetically through mutation, recombination, meiotic drive, and
drift. This genetic explanation of evolution is called the Modern Synthesis.
SLIDE 6. Flies mating, Drosophila genome, and Dobzhansky's quotation
about evolution being able to be explained through population genetics
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The Modern Synthesis is one of the great explanatory principles of biology,
ranking with the germ theory of disease, the gene theory of inheritance, the
chlorophyll theory of photosynthesis, and the cell theory of anatomy and
physiology.
However, this model not tell us all about evolution. First, it assumes, but does
not explain, the types of variation; and second, it can be tested only within the
species. Macroevolution has to be extrapolated from it. If genetics is "Darwin's
missing evidence", then only part of this evidence is being used. Until recently,
the only areas of genetics that were brought to evolutionary biology were
population genetics and molecular genetics. What was missing--and what can
now be added--is developmental genetics (see Gilbert et al, 1996).
III. Explaining Darwin's evidence and how it has been improved
So let's return to Darwin.
Darwin thought that embryology provided the best evidence for evolution.
SLIDE 7. Darwin quotations about importance of embryology, embryonic
homologies
Why did Darwin think embryology was so critical? Because it explained the
similarities between organisms. This similarity of anatomy based on descent is
called homology, and it was the principle of classification proposed by Darwin's
rival, Richard Owen.
SLIDE 8. Sir Richard Owen and the femur of a Moa. Serial homology and
special homology vs. analogy.
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In this view, homology was recognized as being the detailed similarity of
organization that is functionally unnecessary (Amundson, 2001). To Owen,
though, these homologies were explained by the descent of Form from the Divine
idea to earthly incarnations. Owen proposed that God had envisioned the
Archetype of each group of animals and then modified their bodies for the offices
of their earthly existences. Darwin made the archetype the ancestral form, and
proposed that homologies arose by the animals evolving by DESCENT with
MODIFICATION. In this concept, Darwin could explain the similarities of animal
form through descent from a common ancestor, and he could explain differences
in their forms by natural selection in different environments.
SLIDE 9. Limb homologies among vertebrates.
To this end, Darwin quoted the evidence of the premier embryologist of his day,
Karl Ernst von Baer. Von Baer had shown that the embryos of vertebrates look
similar when they are young and diverge as they developed.
{Von Baer actually knew that the earliest stages were different, as between frog
cleavage and fish cleavage.}
SLIDE 10. Karl Ernst von Baer, vertebrate embryos at the "phylotypic
stage", and his quotation that the early embryo is not like lower animals,
but like their embryos.
Von Baer's embryology provided Darwin with the key element to explain
homology and at the same time suggested that homologies were to be found
more readily in the developing organisms than in the adults (see Ospovat, 1981).
In the Origin of Species, he celebrated the case of the barnacle, whose larvae
showed it was a shrimp-like arthropod, and in the Descent of Man, he gloried in
Kowalevsky's discovery that the tunicate--hitherto classified as a shell-less
mollusk--was actually a chordate. It had a notochord and pharyngeal slits that
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came from the same cell layers as those of fish and chicks. The two great
domains of the animal kingdom--invertebrates and vertebrates-- were united-through larval homologies!
SLIDE 11. Darwin quotation from Descent of Man; Agassiz' angry quotation
the same year.
But homology can be a tricky concept. If used alone, it risks forming a circular
argument wherein structures are considered homologous because of common
origin, and these animals are said to have a common origin because they have
homologous structures. One needs to have an independent assessment of
ancestry and origins. As I will show, we have this independent assessment now;
but Darwin lacked it, and the study of macroevolution and phylogeny was
eclipsed by the study of microevolution and genetic variations within species.
I find that I can teach the relationships of homologies and evolution best to my
students by looking at one of the other passengers on the HMS Beagle. This
passenger was a bit older than Darwin, but like Darwin, had been trained in
theology. I am speaking of the Tierra del Fuegan native, York Minster.
SLIDE 12. Theologically trained passengers aboard the Beagle. Both
finished their training in theology in 1830. Charles Darwin and York
Minster.
York Minster had been abducted by Captain Fitzroy on the first voyage of the
Beagle to the southern tip of South America, and Fitzroy had him educated in
London as a missionary. He was now being repatriated to spread the Gospel in
Tierra del Fuego (see Desmond and Moore, 1991). Imagine his education. He
would be told of different religions--Judaism, Catholicism, Russian Orthodoxy,
Lutheranism, and of course, the Anglican Church. There are differences and
similarities. They share similar but different Bibles; sing similar but different
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hymns, worship similar, but different Gods. How is he to make sense of them?
Do these similar religions have a common origin or are they separate acts of
religious faith? No one can go back in time. How would he determine whether the
religions came from a common ancestor and if the similarities are due to this
common origin?
SLIDE 13. Material evidence for common descent. Biblical archeology for
religious diversity; paleontology for biodiversity: Herod's palace,
Archeopterix.
Evidence 1: material artifacts showing shared histories and transitions. The
Tierra del Fuegan would have the evidence of archaeology. He could be shown
concrete evidence of religious history. Here we see Herod's palace. Just as
archeology can reveal the history and genealogy between religions, so can
paleontology reveals the history and transitions between groups of animals.
(Footnote 1: Paleontology and Archaeopterix)
SLIDE 14. Vestigial apparatuses and common descent. Would the story of
Ahab been independently formulated in Jewish and Christian Bibles?
Would the aortic arch have been independently created in fish and
mammals?
Evidence 2. Vestigial apparatuses. York Minster might argue that Christianity has
lists of Semitic kings that would not be in its theology were it not for its inclusion
in an earlier religion. The fact that such unlikely stories such as that of Onan,
Samson, Ahab and Jezebel occur in both the Hebrew Bible and the Catholic
Bible would suggest a common origin. Similarly, Darwin could argue that such a
strange thing as the aortic arches would not be in mammals and amphibians
were they not in earlier ancestors from which they arose. You would not invent
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the aortic arches twice, especially when most of the mammalian aortic arches
degenerate.
Thus, Darwin and his colleagues could draw branched-chain evolutionary trees
of the vertebrates based on embryonic homologies, adult homologies, vestigial
apparatuses, and the fossil record. Today, our model looks something like this.
SLIDE 15. Cladogram of vertebrates
But in the late 1800s, there were many variants, especially dealing with the
affinities of each reptile group to one another. This shows a genealogical
connection amongst all the tetrapods
York Minster could also draw such a cladogram of religions, based also on
homologies, vestigial apparatus, and material artifacts.
SLIDE 16. Cladogram of religions. Note that the first separation is between
the Jewish and Christian clades. Then there is a division in the Christian
clades between the Eastern and Western Churches. Then there is a split in
the Western Church between Catholicism and the protestant
denominations.
But while this is the accepted tree, he could also draw another one--depending
on which characteristic was primary and which secondary.
SLIDE 17. Variant cladograms of religion. The one on the left is as the
earlier slide. The one of the right has Protestantism and Orthodoxy
together, branching off from Catholicism. Instead of east/West distinction,
the cladogram is made on the Papacy/Non-papacy distinction.
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How could he decide? Why do we know that the model on the left is correct and
the model on the right is wrong? Here, York Minster had a huge advantage over
Charles Darwin. There were textual records for the histories of the churches.
SLIDE 18. Luther's 95 Theses; comparison of chick and turtle fibroblast
growth factor genes.
Evidence 3. Historical records. York Minster might say that the best evidence is
neither from material artifacts or from vestigial apparatus, but from textual
evidence. In religions, this would be the set of documents demonstrating the
splitting of one religion into two or more new religions. Henry VIII's 1534 Act of
Supremacy and Luther's 95 Theses would be such documents, showing the
separation of Protestant Christianity from Catholicism and not from Orthodoxy.
And here is where macroevolution, the study of phylogeny, of evolution
above the species-level, hit a wall. It did not have such documentation. Except
for the fossil record--which was much worse for Darwin than it is for us today---there was no independent assessment for common origins. (As to the fossil
record, recall that Roy Chapman Andrews' expeditions to Mongolia were in the
1920s, as were Romer's expeditions to Patagonia; good examples of fossilized
whale precursors were only found in the 1990s). Not until the arrival of molecular
genetics would evolution have a meaningful way of getting around the homology
question.
It wasn't until 1977--Maxam and Gilbert--that we could access the historical
records of the genes. It has turned out to be a treasure trove beyond measure. It
works by finding rare and shared molecular similarities, which, like the Ahab
story, would not be expected independently.
SLIDE 19. DNA transposons showing linkage of whale and hippo and the
linkage of that clade to cow and sheep. Transposon insertions 4, 5, 6, and 7
are found only in whale and hippo DNA and not in any other group.
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Transposon insertions 10 and 12 are found in this group plus the
artiodactyls (cow and deer).
This slide shows an analysis of DNA transposons--collections of DNA that have
no known function and which can rarely leave their place of origin and insert into
a different region of the genome. If they migrate into an existing gene, they can
knock out the gene's function. But most of the time, if they migrate at all, they
migrate to regions of DNA that aren't being used. Most of the sequences are
held in common by all mammals. However, some are informative. That the pig
and peccary are related has never been disputed, but the molecular order of the
transposons does put them together in a common group. Similarly, anatomical
evidence has long been used to link cattle and deers into a common clade, and
this was also confirmed by the molecular data. However, the molecular data
showed that the whale and hippopotamus are related and that both arose from
an ancestor in common with the cow and deer. This supported one of several
possible ideas. So we now have an independent measure of common ancestry.
(Footnote 2: cladograms of religion)
(Footnote 3: whales)
IV. The hijacking of evolutionary embryology
But Darwin and his immediate successors lacked this. In the absence of this
independent assessment, the field of evolutionary embryology collapsed. Worse
than collapsed--it was hijacked.
If there were a Modern Synthesis, there would have to have been some
UnModern Synthesis. This unmodern synthesis was called the Biogenetic Law,
and it was proposed by Ernst Haeckel. He claimed that ontogeny--the
development of the individual--recapitulated phylogeny--the evolution of the
species.
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SLIDE 20. Haeckel--evolutionary "tree" with privileged axis to man (not
woman)
According to Haeckel, evolution was not a branched bush, it was a linear chain.
The embryo was a truncated version of the adult form of a more primitive
species. Each animal evolved by adding a new terminal phase to the pre-existing
embryonic phases. Thus, the ape and the human did not share a common
ancestor; rather, the most primitive human arose from the most advanced ape.
SLIDE 21. Ontogeny recapitulating phylogeny
Here is Haeckel's view: The entire animal kingdom is but the dismembered
stages of the human embryo. Embryos of advanced species pass through
(recapitulate) the adult forms of more primitive species. Contemporary animals
are the way our descendents used to be!
The Biogenetic Law had three components:
1. Law of correspondence: Correspondence between fertilized egg and the
amoeba; between the gastrula and the coelenterates; between the pharyngula
and the fish.
2. Law of terminal addition: Evolution by adding on terminal stages.
3. Law of truncation: Truncation to allow for normal time of gestation.
This is very different from the Darwinian view (see Gould, 1977).
SLIDE 22. Evolutionary theory of biodiversity as branched bush, not linear
chain.
Creationists claim that evolutionary biologists have labored under a Haeckelian
delusion.
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SLIDE 23. Haeckel's infamous picture. Compared with current pictures
(from Ken Miller's website) of chick, fish, pig, and human embryos. Racist
claims of Haeckel.
They claim that Haeckel made an inaccurate diagram, that evolutionary
biologists have known this diagram was mistaken, and this use of this diagram
demonstrates how poor the evidence is for evolution. (That is to day, evolutionary
biologists have nothing else, so they will use this false diagram). The diagram is,
of course wrong. But it has been used ever since Romanes (1901) as a
simplification of von Baer's rules. All vertebrates do go through a stage where
they have pharyngeal pouches and slits, a notochord, dorsal neural tube, and
somites. The just happen to do it at slightly different times, so that in some
instances the limbs have formed, in other instances they haven't, and so forth.
The animals don't look identical. But they are similar in those things that
distinguish chordates from other phyla.
So they have several points. One is that Haeckel was a biologist who
faked his data. Actually, Haeckel's crimes are actually far worse. (Same slide)
First, he and his followers took evolutionary biology from the Darwinian
notion based on von Baer to his own recapitulationist view.
Second, Haeckel was a German supremacist who believed that the Aryan
race had the right to extinguish others. He was a member of the ultra-right wing
Thule Gesselschaft, which was one of the precursors of the Nazi party. The fact
that Haeckel falsified evolution is not a point against evolution. He had a political
agenda to which he shaped evolutionary biology (see Gould, 1977; Gasman,
1971).
And so it is not surprising that this view turned out to be wrong. It was
based on poor embryology and a progressivist ideology. It was not evolution as
Darwin knew it. It was wrong, and was proven wrong. Exceptions to the rule
mounted up. Indeed, von Baer was arguing against this view literally before
Haeckel was born. (Recapitulation did not originate with Haeckel. He popularized
it and made it more "scientific"). The ideology became suspect--humans were
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never rabbits or squids; there was no physiological mechanism for it; and its
racism was becoming apparent.
It is therefore is also not surprising that serious scientists questioned it. Indeed,
evolutionary embryology came to a grinding halt. Many of its practitioners went
into a new area that promised a better handle on inheritance and evolution-namely genetics.
SLIDE 24. Quotations about the demise of evolutionary embryology.
Bateson, especially, viewed genetics and succeeding morphology.
The Creationists' claims that evolutionary biologists used Haeckel's discredited
diagram because they had so little data is totally wrong. First, not many biologists
had realized these diagrams had been discredited. While Haeckel was viewed
with suspicion, Romanes had used these pictures and most authors had quoted
Romanes as their source. Second, evolutionary biologists have data galore. The
more interesting point is that since Creationists can no longer challenge
evolutionary biologists on their data, they attack their textbook pictures instead.
Footnote 4: Wells' critique of Haeckel's drawings.
But it was Stephen J. Gould, who in 1977, finally put an end to the tradition of
recapitulation in developmental biology.
SLIDE 25. Gould photo.
In Ontogeny and Phylogeny, Gould brought all the facts together and
demonstrated how Haeckel had stolen the field of evolutionary embryology. This
was the second publication of 1977. The first half of this book is exorcising
Haeckel's ghost so that some other theory could be put in its place. He proposed
his own hypothesis; but that same year, 1977, Nobel Laureate François Jacob
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proposed another hypothesis upon which much of evolutionary developmental
biology would be based.
Slide 26. François Jacob. Bricolage catalogue.
1. Evolution was bricolage--tinkering--not engineering. It used what was
available.
2. One should look at evolution not in the adult animals but in the developing
animals. Evolution works not only on adults but also on the recipes for the adults.
Look at changes in regulatory genes, not structural genes.
Here, he was returning to a model proposed by Richard Goldschmidt --evolution
was the inheritance of changes in development.
SLIDE 27. Goldschmidt. View that development is change in functional
biology over time; evolution is change in development over time. To go
from functional biology to evolution without development is like going from
displacement to acceleration without velocity.
When we say that the present-day one-toes horse evolved from a five-toed
ancestor, we are saying that during the evolution of the horse, the placement and
differentiation of cartilage cells has changed. This notion that evolution was the
inheritance of changes in development works whether one thinks of the changes
in the horse foot or the number of bristles on the back of a fruit fly.
Jacobs' view was also based on some of the pioneering work of Alan Wilson,
who showed the discrepancy between genetic evolution and morphological
evolution. One could get major changes in morphology with relatively small
changes in genes. One way of explaining this discrepancy (and one that has
worked remarkably well--as we will see) was to posit that there were regulatory
genes acting in the embryo, which controlled the development of particular
structures (King and Wilson, 1975; see Gilbert, et al. 1996;).
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V. The return of evolutionary developmental biology
The events that come now are very rapid. The first discoveries in evolutionary
developmental genetics showed the remarkable homology of genetic
instructions. Indeed, the developmental instructions for forming several
analogous organs were shown to be homologous.
For instance, the fly eye and mouse eye have very little in common as to their
origin or structure. However, Walter Gehring's group demonstrated that the
instructions to form both eyes are based on a set of homologous genes such as
Pax6.
SLIDE 28. Pax6 expression in the Drosophila eye/antenna imaginal disc,
and its absence in eyeless mutants. Mouse Pax6 expression in the
embryonic eye, and its absence in loss of function Aniridia mutants.
The instructions are so similar that fly imaginal discs will form an eye (a
Drosophila eye) when given the rodent Pax6 gene.
SLIDE 29. Ectopic fly eyes made by activating murine Pax6 in insect jaw
imaginal disc. (Halder et al., 1995).
Thus, whereas it was previously thought that eyes formed independently over 40
different times, we now find that each type of eye is but a variation on a theme.
By the early 1980s, the Hox genes of insects and vertebrates were shown to be
homologous.
First--(just like in the vertebrae) there was serial homology between the genes
within a species. They could be seen as variants of ancestral Hox genes.
Second, special homology between a particular Hox gene in one phylum and that
similar Hox gene in another phylum.
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Third, the entire Hox complex appears to be similar in nearly every organism
studied. Even their expression patterns are similar. These could not be
accounted for by convergent evolution.
Footnote 5: Wells, Behe and the argument against genes
SLIDE 30. Derivation of the homologous Hox genes of insects and
vertebrates. (Holland and Garcia-Fernandez, 1996).
Nature uses the same sets of genes in different ways. We specify our anteriorposterior axis in the same way as fruit flies. But we obviously use the genes
differently. We don't make wings or antennae.
SLIDE 31. Expression patterns of head and trunk genes in flies and
mammals. Same "head genes" used. (Hirth and Reichert, 1999).
So there must be important differences as well as important similarities. If we are
talking about descent with modification, we expect both underlying similarities
and secondary differences. Can these differences in developmental genetics
explain morphological differences?
We're just beginning--and it's fascinating.
Here's one example--from Sean Carroll's lab here in Madison. Why do insects
have only six legs while other arthropods have many more? The answer appears
to involve one of those Hox genes.
SLIDE 32. Ubx changes distinguish insect clade. (Galant and Carroll, 2002.)
In the insect clade--and only in this group-- has there been a mutation in the
Ultrabithorax gene. This mutation allows Ultrabithorax to repress Distal-less gene
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expression. Distal-less is critical in the formation of limbs. Ubx is thus able to
repress limb formation in the abdominal segments of the fly. Thus, the insects
have six thoracic legs; not eight legs like spiders, not ten legs like crabs, and not
dozens of legs like centipedes. Mutations in regulatory genes can give them new
properties.
(Note that the six-leggedness is not used as a homologous entity here. The
cladogram that this trait is superimposed upon is the cladogram derived from
molecular genetics and other morphological traits. The circularity is avoided by
the independent assessment of gene sequences.)
But one doesn't need a mutation in the actual protein. A change in where the
protein is expressed can also be critically important. Here's one of my favorite
examples. How does the duck get its webbed feet?
It’s a matter of gremlin gene expression.
SLIDE 33. Gene expression patterns in duck and chick hindlimbs. BMP4
activates apoptosis; but gremlin can inhibit BMP4. If present, it should
prevent apoptosis and allow webbing to be retained. (Merion et al., 1999.)
Can you get webbed feet if you add gremlin to the interdigital space?
YES.
SLIDE 34. Addition of Gremlin-containing bead to the interdigital space
inhibits BMOP signaling and allows webbing to be retained. (Merino et al.,
1999.)
So Jacob's model yielded some interesting results. Change the expression
pattern of a gene and you can get new structures. This is something my students
can understand. Emphasizing changes in gene expression in an embryo is a
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better way of explaining evolution than looking at changes in gene frequencies
within populations.
Changing the pattern of regulatory gene expression has also been shown to
correlate with the type of vertebra formed by the somites, and the type of
appendage formed by crustaceans.
Here's another example from Madison, Wisconsin--how to get feathers form
scales.
SLIDE 35. BMP2 and SHH expression in the scale and feather rudiments.
(Harris et al., 2002)
What about the creation of a new morphological structure--a novelty. Avian
feathers have long been proposed as an evolutionary novelty. But the
mechanism to produce feathers has remained elusive. However, a paper recently
published from John Fallon's laboratory provides a developmental mechanism by
which feathers can be generated from scales. They provide evidence that the
differences in the expression of sonic hedgehog and BMP proteins separate the
feather from the scale. Both the scale and the feather start off the same way,
with the separation of BMP2 and SHH- secreting domains. However, in the
feather, both domains shift to the distal region of the appendage. Moreover, this
pattern becomes repeated serially around the proximal distal axis. The
interaction between BMP2 and Shh then causes each of these regions to form its
own axis--the barb of the feather.
Matt Harris and others in the Fallon laboratory have shown that when you alter
the expression of Shh or BMP2, you change the feather pattern. The results
correspond exceptionally well to a proposed mechanism of feather production
from archosaurian scales.
Footnote 6: feathers
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Another question in evolutionary biology concerns how mammals formed
different types of teeth. Indeed, tooth morphology is critical to mammalian
classification.
Jukka Jernvall and colleagues in Irma Thesleff's laboratory at the University of
Helsinki have pioneered a computer-based approach to phenotype production
using Geographic Information Systems--the technology that ecologists use to
map the location of vegetation of hillsides. They have used this technology to
map gene expression patterns of incipient tooth buds--literally turning a mountain
into a molar. They have shown that gene expression patterns forecast the exact
location of tooth cusps and that the differences in teeth between mouse and vole
are predicated upon differences in gene expression patterns.
SLIDE 36.Tooth morphogenesis and gene expression (Jernvall et al., 2000)
1. The left side of the slide shows the fossil record of rodent teeth, demonstrating
that the vole retains the diagonal patterning of cusps, while the mouse has
evolved an orthogonal cusp pattern.
2. The right side shows the developmental topology of tooth cusp formation. The
mouse develops its orthogonal cusps on embryonic day 16; the day the vole
develops its diagonal cusps.
SLIDE 37. Gene expression patterns predict by about a day where the
cusps will be. They differ between species. (Jernvall et al., 2000.)
On embryonic day 15, the mouse has but one cusp, but gene expression
patterns of the enamel knot genes (Fgfs and Shh) show that a second cusp will
form orthogonally. Similarly, on embryonic day 15, the vole molar has but one
cusp, but the gene expression pattern shows that a second cusp will form
diagonally.
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In a recent paper, Jernvall and his colleague Salazar-Cuidad propose a
mathematical model for these differences, wherein small changes in a gene
network, again working through the interactions of BMPs and SHH--can account
for the different tooth morphologies.
They can generate different tooth morphologies by just changing the reaction
kinetics of diffusion.
SLIDE 38. Mathematical modeling of gene expression patterns. (SalazarCiudad and Jernvall, 2002.)
They find that a small increase in the bias of lingual growth and a stronger
binding constant of inhibitor is sufficient to change the vole pattern of tooth
growth into that of the mouse. Moreover, large morphological changes can result
from very small changes in initial conditions. Another conclusion is that all the
cells can start off with the same sets of instructions. The specific instructions
emerge as the cells interact. The model also predicts that some types of teeth
are much more likely to evolve in certain ways and not in others. These
predictions have been born out.
Footnote 7. Personal opinions.
SLIDE 39. Evolution of the vertebrate jaw (Kuratani, et al., 2001)
The last example involves the formation of another evolutionary novelty, he
vertebrate jaw. This was one of those problems of evolutionary embryology that
couldn't be decided in the early 1900s. Shiguro Kuratani has shown that the oral
apparatus of the jawed vertebrates is not derived from the oral apparatus of the
lamprey, as had long been thought. In the lamprey, the naso-hypophyseal plate
is retained and prevents the migration of neural crest cells rostrally. In jawed
vertebrates, this plate separates very early in development into the nasal and
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hypophyseal neural tissues, thereby making a path for the rostral migration of
neural crest cells. This permits the formation of a new structure, the jaw.
As Dr. Kuratani ends a recent paper:
"The clue to solve this problem, therefore, will not be obtained by comparative
anatomy of the adult structures, but rather by discrimination of conserved and
newly acquired patterns of gene expression…Molecular developmental biology
has taken the initial steps into this old question of comparative zoology, but it has
already suggested new directions in which a solution may lie."
The developmental genetic approach to evolution complements the traditional
population genetic approach. They are both needed.
SLIDE 40. New evolutionary synthesis
This slide summarizes differences between the population genetic and
developmental genetic approaches. Both are critical and necessary for evolution.
Many critics pointed out that population genetics cannot directly explain
macroevolution. But when you add developmental genetics to the theory, you
have a wonderful robust mix that can explain both evolution both within species
and in higher taxa. It turns out that we humans are closer to other animals than
we thought, and that the mechanisms by which the living world is generated are
highly conserved.
SLIDE 41. Biodiversity and Biohomology (picture from the Biohistory
Research Hall).
Our remarkable phenotypic biodiversity is underlain by an equally
remarkable biohomology.
I think that students (and their parents) will be able to readily
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understand evolution when presented as changes in gene expression
more readily than when presented as changes in gene frequency. One
can visualize these changes and thereby acquire an excellent way to
recall this information. Moreover, for most non-scientists, evolution is
about macroevolution, and the changes by which reptiles become
mammals or fish become land-dwelling tetrapods is more to the point
than how moths or beetles become a different colored moth or beetle.
We can now merge developmental genetics and population genetics to
explain the biodiversity of life on earth, and, as Darwin said, "there is
grandeur in this view of life."
Thank you.
23
Cited references:
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Alters, B. J. and Alters, S. M. Defending Evolution: A Guide to the Creation/Evolution
Controversy. Sudbury, MA.
Amundson, R. A. 2001. Adaptation, development, and the quest for common ground. In
S. Orzack and E. Sober, (eds) Adaptationism and Optimality. Cambridge University
Press.
Behe M. J. 1996. Darwin's Black Box: The Biochemical Challenge to Evolution. Free
Press, NY.
Darwin 1859. On the Origin of Species. John Murray, London.
Darwin 1874. The Descent of Man, and Selection in Relation to Sex. 2 vols, (second ed.)
John Murray, London.
Desmond, A. and Moore. J. 1991. Darwin: The Life of a Tormented Evolutionist. Norton,
NY.
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insect Hox protein. Nature 415: 910 - 913.
Gasman, D. 1971. The Scientific Origins of National Socialism. Macdonald/American
Elsevier.
Gilbert, S. F. (1988). Cellular Politics: Just, Goldschmidt, and the attempts to reconcile
embryology and genetics, In The American Development of Biology (ed. R. Rainger, K.
Benson, J. Maienschein) University of Pennsylvania Press, Philadelphia. pp. 311-346.
Gilbert, S. F. and M. Faber. 1996. Looking at Embryos: The Visual and Conceptual
Aesthetics of Emerging Form. In Tauber, A. I (ed.), The Elusive Synthesis: Aesthetics and
Science. Kluwer, Dordecht. p.128.
Gilbert, S. F., Opitz, J., and Raff, R. A. (1996). Resynthesizing evolutionary and
developmental biology. Developmental Biology 173: 357 - 372.
Gould, S. J. 1977. Ontogeny and Phylogeny. Harvard University Press, Cambridge.
Grant, P.R. 1986. Ecology and Evolution of Darwin's Finches. Princeton University
Press, Princeton, NJ.
Halder, G., Callaerts, P., and Gehring, W.J. 1995. Induction of ectopic eyes by targeted
expression of the eyeless gene in Drosophila. Science 267:1788 - 1792.
24
Harris, M. P., J. F. Fallon, and R, O, Prum. 2002. Shh-BMP2 signaling module and the
evolutionary origin and diversification of feathers. J. Exp. Zool./Mol. Dev. Evol. 294: 160
- 176.
Heschel, A. J. 1955. God in Search of Man: A Philosophy of Judaism. Farrar Straus &
Cudahy, New York.
Hirth F. and Reichert H. 1999. Conserved genetic programs in insect and mammalian
brain development. BioEssays. 21: 677 - 684.
Holland, P. W. H. and Garcia-Fernández, J. 1996. Hox genes and chordate evolution.
Dev. Biol. 173: 382 - 395.
Jacob, F. Evolution and tinkering," Science 196: 1161-1166
Jernvall, J., Keranen, S.V., and Thesleff, I. 2000. Evolutionary modification of
development in mammalian teeth: quantifying gene expression patterns and topography.
Proc. Natl. Acad. Sci. USA. 97: 14444 - 14448.
King, M. C. and Wilson, A. C.1975. Evolution at two levels in humans and
chimpanzees. Science 188: 107 - 116.
Kuratani S, Nobusada Y, Horigome N, Shigetani Y. 2001. Embryology of the lamprey
and evolution of the vertebrate jaw: insights from molecular and developmental
perspectives.
Philos. Trans. R. Soc. Lond. B (Biol. Sci.) 356: 1615 - 1632.
Maimonides. (Moshe ben Maimon).1190. The Guide for the Perplexed. tr. Shlomo Pines
(Chicago, 1963).
Maxam, A. and W. Gilbert , "A new method for sequencing DNA." Proc. Natl.
Acad. Sci. U S A. 74: 560-4.
Merino, R., Rodriguez-Leon, J., Macias, D., Ganan, Y., Economides, A. N., Hurle, J. M.
1999. The BMP antagonist Gremlin regulates outgrowth, chondrogenesis and
programmed cell death in the developing limb. Development 126: 5515 - 5522.
Pigliucci, M. 2002. Denying Evolution: Creationism, Scientism, and the Nature of
Science. Sinauer Associates, Sunderland, MA.
Ospovat, D. 1981. The Development of Darwin's Theory: Natural History, Natural
Theology, and Natural Selection, 1838-1859. Cambridge University Press, Cambridge.
Romanes, G. J. 1901. Darwin and After Darwin. Open Court Publishing, London.
25
Salazar-Ciudad I, Jernvall J.2002. A gene network model accounting for development
and evolution of mammalian teeth. Proc. Natl. Acad. Sci. USA 99: 8116 - 8120.
Wells, J. 2000. Icons of Evolution: Science or Myth? Regnery, Wshington, DC.
26
Footnotes
1. Paleontology has been critical in the evolution debate for over a century. It was critical
in abolishing the idea of a single act of creation. Dinosaurs and humans are both land
vertebrates, but their respective fossils are in separate strata. Those rocks containing
dinosaur fossils are invariably older than those containing human fossils. Similarly,
fossils of oceanic trilobites and bony fish are plentiful in the geological record, but they
are never found together. The fish emerged long after the trilobites became extinct. The
fact that most fossil species are no longer extinct also argues against modern Creationist
views such as "Intelligent Design." Intelligent Design ("ID") denies evolution and also
rejects the "young earth" hypothesis that the world is less than 10,000 years old. In this
view, life is irreducibly complex and each species is miraculously created by separate
acts of God. However, given that most of the species on earth are not here now, this view
of God makes the Creator either incompetent or evil. (For some of the statements of the
Creationists and how they twist science, definitely see
http://www.actionbioscience.org/evolution/nhmag.html;
http://www.millerandlevine.com/km/evol/index.html; Alters and Alters, 2001;
http://www.talkorigins.org/faqs/wells.html; Pigliucci, 2002). Jonathan Wells, in his
notoriously inaccurate book Icons of Evolution (2000), tries to make the claim that
Archeopterix is not a good transition species. Wells claims that there are problems over
the dating of Archeopterix, but this is a difference between 150 million years and 124
million years. Moreover, more fossils showing the bird-dinosaur connection have
recently come from China. One of them, the Dromeosaur, is a small bipedal dinosaur
with different types of feathers. Paleontology also provided independent evidence for
assessing homologies, and this was especially important prior to molecular genetics. No
one can "prove" a transition forms to a Creationists, because if you have two Divinely
inspired types, A and B, a given animal will be either in class A or class B. Moreover, if
you posit a particular animal as being "between" them, you now have two gaps rather
than one.
2. The use of Western religion to demonstrate cladistics goes far beyond this example.
For instance, the separation of the Anglican Church and the Episcopal Church is a good
example of geographic isolation. The closely related churches of the Anglican
Communion (Anglican Church, Episcopal Church, Anglican Church of Canada, the
Spanish Reformed Episcopal Church, etc.) represent a group of species within a genus.
One could imagine Angicus anglicus, Anglicus episcopaliensis, Anglicus canadiensis, etc.
Moreover, the argument over whether religious similarities are due to shared ancestry or
separate acts of creation is not a straw man argument. There are real controversies about
this. Indeed, this argument frames the controversy between orthodox Mormon scholars
(who claim that Jesus appeared separately in the United States and that an angel of God
gave to mankind a new gospel, the Book of Mormon) and secular scholars (who claim
that the similarities between Mormonism and other western religions is because
Mormonism is an offshoot of American Protestantism with which it has common
ancestry.
27
3. We now have remarkable fossil evidence concerning the evolution of whales from
terrestrial animals. Interestingly, the fossils of Pakicetus, Ambulocetus, and Indocetus
indicate that for all their similarities to whales and dolphins, these were probably
terrestrial mammals that lived in shallow rivers and lakes. Pigliucci (2002) points out that
today's hippos might be at a stage where they may become fully aquatic animals. Their
babies swim before walking, the mother nurses the young underwater, the male's testicles
remain inside the body, they are relatively hairless, and they do not sweat. Creationists,
especially those identifying themselves with Intelligent Design, have to deny that genes
have anything to do with evolution (since evolution does not occur). Thus, the Creationist
philosopher Paul Nelson will claim that biologists' definitions of homology are
tautological and we have no way of knowing whether or not a structure is similar by
common ancestry, special Creation, or similar environment (homoplasy). This is not so,
because we can access the historical record in the genes. Nelson
(http://www.arn.org/docs/odesign/od182/hobi182.htm) will use the same quotations used
here (by Sedgewick and Russell) to urge that developmental biology return to a gene-less,
more embryological, past. For Nelson and Wells, two of the major Creationists of the
Discovery Institute of Seattle, WA, were supposed to have a poster at this year's SDB
meeting. It is abstract 18 "Recovering the classical tradition in comparative embryology."
They did not come to present or defend it. For more, see
http://www.talkorigins.org/faqs/wells; http://www.nmsr.org/iconanti.htm; Pigliucci,
2002).
4. Creationist Jonathan Wells was trained in developmental biology. He is also a follower
of the Reverend Sun Myung Moon (whom he addresses as "Father"), and he identifies
with the Unification Church. Wells claims to have pursued his doctorate in biology so
that he could "destroy Darwinism" and its evils (see Pigliucci, 2002). His address on this
is at http://www.tparents.org/library/unification/talks/wells/DARWIN.htm. Wells (2000)
makes the rather strange claim that since Haeckel's erroneous picture has been reprinted
in biology books for so long, evolutionary biology must have been based on it, and
therefore all of evolutionary biology is wrong. Most biologists had been willing to use
this illustration as an oversimplification of von Baer's laws to illustrate that embryos pass
through similar stages. Once Richardson published the actual pictures of the embryos,
reprinting this picture became silly, and almost immediately the textbooks changed. My
website (zygote.swarthmore.edu) amended the figure within a month of the appearance of
Richardson's article. So did the website that Ken Miller had for his introductory biology
book. Other books, especially those without websites, had to wait longer. For more, see
Ken Miller's website (http://millerandlevine.com/km/evol/embryos/Haeckel.html) and the
http://www.talkorigins.org/faqs/wells site. The assertion that evolutionary biologists
knew that these pictures were fraudulent but used them anyway is also wrong. I am a
developmental biologist who also has a masters degree in the history of science. When I
wrote the first editions of my textbook, I did not know they were wrong. In fact, I hadn't
realized they were from Haeckel, and I quoted the Romanes (1901) volume as my source
of the picture (see Gilbert 1988, p. 153).
28
5. In order for Creationism to work, genes can't have anything to do with morphology. If
genes control morphology, than changes in genes can cause changes in morphology, and
that's evolution. So Creationist Jonathan Wells (see footnote 4) has an example so
ludicrous that it would be funny if it weren't such a sneaky slight-of-hand. In his talk
(accessible at http://www.tparents.org/library/unification/talks/wells/DARWIN.htm),
Well states, " According to the standard view, the development of an embryo is
programmed by its genes-its DNA. Change the genes, and you can change the embryo,
even to the point of making a new species. In the movie "Jurassic Park," genetic
engineers extract fragments of dinosaur DNA from fossilized mosquitoes, splice them
together with DNA from living frogs, then inject the combination into ostrich eggs which
had had their own DNA inactivated. In the movie, the injected DNA then re-programmed
the ostrich to produce a dinosaur. Experiments similar to this have actually been
performed, though not with dinosaur DNA. In every case, if any development occurred at
all it followed the pattern of the egg, not the injected foreign DNA. While I was at
Berkeley I performed experiments on frog embryos. My experiments focused on a
reorganization of the egg cytoplasm after fertilization which causes the embryo to
elongate into a tadpole; if I blocked the reorganization, the result was a ball of belly cells;
if I induced a second reorganization after the first, I could produce a two-headed tadpole.
Yet this reorganization had nothing to do with the egg's DNA, and proceeded quite well
even in its absence (though the embryo eventually needed its DNA to supply it with
additional proteins). So DNA does not program the development of the embryo."
When a philosophy professor emailed me, asking if this could be true, I answered (in
part) as follows:
"Damn, Wells! He's taken away my emergency retirement plan! I figured that if I
ever needed money after retirement, I could come out as a new-born Christian
Creationist. I could live off the royalties of the book I would write and get plenty of free
travel all over the world!! And now Wells steals my idea! One of the things I could
write about is how DNA doesn't control the phenotype, and hence, evolution can't be
possible. And it would be so easy to do. One of my examples would be the one that Wells
uses. Here, by merely rotating the egg, you can get two heads--a major phenotype if ever
there were. And genes had nothing to do with it. Moreover, if I blocked cytoplasmic
rotation, I wouldn't get a head. Again, genes don't play a role at all. It is such a neat story.
And the explanation is so simple, but not obvious to the person who hasn't had
biological training. Here's the trick: The early development of many embryos (esp.
Xenopus and Drosophila) doesn't have a thing to do with the nuclear genome. The
nuclear genome isn't even active until the 12 division or so. Rather, the early
development of the frog or fly has to do with its mother's genes! This was discovered by
Sturtevant (in snails) in 1923 (Inheritance of direction of coiling in Limnaea. Science 58:
269-270; http://devbio.com/chap08/link0803.shtml), and it was for her studies on the
molecular bases for maternal inheritance in Drosophila that Nüsslein-Volhard won the
Nobel Prize in 1995.
So what's going on in Xenopus? Basically, it's this: The egg is provisioned by the
mother with numerous mRNAs and proteins (from her genome). Three important proteins
put into the egg by the oocyte genome are beta-catenin, Dishevelled, and GSK-3. They
29
are all components of the Wnt signaling cascade. (1) GSK-3 will tether beta-catenin to a
proteolysis complex and cause -catenin's degradation. (2) Dishevelled protein will block
GSK-3, thereby protecting -catenin. (3) If -catenin is not degraded, it is able to enter
the nucleus. (4) There, it acts as a transcription factor to activate certain genes (of the
embryonic frog) to transcribe the messages that become the Siamois and Goosecoid
proteins. (5) These are the proteins that specify the dorsal axis of the frog embryo (the
neural tube, head, etc.) I.e., they are proteins which are involved in forming the
Organizer. (All this can be found on pages 308-322 of the 6th edition of my textbook).
So what does cytoplasmic reorganization have to do with it? Everything. Originally,
beta-catenin and GSK-3 are present throughout the egg cytoplasm. Dishevelled, however,
is confined to the cortical (outer) cytoplasm at the vegetal pole. The end result is to get
beta-catenin active only on the dorsal side of the embryo, and not on the ventral side. If it
is active on the ventral side as well as on the dorsal side, two heads will form, because the
beta-catenin would allow the specification of Organizers on both sides of the embryo.
Conversely, if beta-catenin were prevented from getting into the nuclei on the dorsal side,
that side would be come ventral tissue, and the embryo would become a bellypiece,
lacking neurons and a head. So the newly fertilized frog egg actually rotates. The sperm
organizes a set of microtubules that form a track allowing the cortical cytoplasm (on the
outside of the egg) to rotate 30 degrees with respect to the yolky internal cytoplasm.
Now, lying at the bottom pole of the unfertilized egg, tethered to the cortical
cytoskeleton, is a packet of Dishevelled protein. Upon rotation, this packet of Dishevelled
is translocated 30 degrees, and ends up pretty much opposite the point of sperm entry. It
is then released from the cortical cytoplasm and diffuses outward into the vegetal
cytoplasm. At this time, GSK-3 becomes active, and it begins destroying all the betacatenin found in the egg. However, in the future dorsal portion of the egg, GSK-3 is
blocked by the Dishevelled protein. Therefore, beta-catenin is preserved, and it can enter
the nucleus. Once inside the nucleus, it can activate the genes necessary for the dorsal
development of the frog embryo. (See picture on P. 321 of my text). If the cortical
rotation is blocked, no head will form. If the egg is rotated 90 degrees after its initial
rotation, the yolk is displaced, and another area will experience Dishevelled protein, and
two Organizers will form, leading to two heads.
No magic, no mysticism. Just a wonderful provision by the mother's oocytes. Of course
the tethering of the Dishevelled protein to the vegetal pole, etc, are all under genetic
control; but it is the genetic control of the mother's genome, not the embryos. The frog
embryo has also evolved its yolky cytoplasm both to provision the embryo with food, and
to serve as a ballast making sure that the internal cytoplasm doesn't rotate. It's a beautiful
case of an organism's development adapting to its environment.
As far as I'm concerned, Wells (and for that matter, Behe) know all about this stuff, but
are able to go far and fast by pulling the wool over the eyes of a population that has no
idea what's going on inside the embryo."
Similarly, Behe (1996) tries to make the point that the eye to complex to have evolved.
However, he never once mentions the studies on Pax6, showing that the instructions for
eye formation are very much the same throughout all animals. Instead of having to arise
30
de novo over 40 times, the instructions to form eyes probably evolved only once and
were modified many times.
6. Feathers are another novelty that Creationists (even today's!) say cannot have evolved.
Paul Nelson's website on design (http://arn.org/docs/odesign/od/ls172,htm) quotes a
particular scientific study wherein the author of the study acknowledges that most
approaches to the origin of feathers ask "why" they evolved, not "how" they evolved.
Agreed, this is because most evolutionary biologists have used a population genetics
approach and have looked at the fitness of a trait in adult populations. However, now we
can revisit these questions using developmental genetics. It will be interesting to see if
the Harris et al. paper ends up on Nelson's site.
7. Should anyone wish to know my personal opinions about religion and science, I should
be up front about them. I have been a religion major (as well as being a biology major) at
Wesleyan University, so I have a longstanding interest in these issues. I have been , at
various times in my life, a Reform, Conservative, and (now) Reconstructionist Jew, and I
have found the views of two Jewish philosophers helpful in formulating my opinions
about science and religion. Others might find them useful, too. The first view comes from
the 12th century rabbi-philosopher-physician Maimonides. In Guide for the Perplexed,
Maimonides noted that a pious man of his time would say that an angel of God had to
enter the womb of a pregnant woman to mold the organs of the fetus. This would
constitute a miracle. But, he added, how much more of a miracle would it be if God had
so empowered matter to be able to create the organs of a fetus without having to employ
an angel every time? I find this a fascinating compromise. Our job as developmental
biologists is to find out how matter--whether divinely ordained or not-- can organize
itself into embryos. (The fact that matter can do this without divine intervention is
remarkable and indicates that we should pay more respect to matter than we usually do.)
The second philosopher is Abraham Joshua Heschel, who noted that science and religion
are not the same, but they are related. Using his works, one can create a "genealogy" of
science and religion, showing their "common ancestry" in the concept of "Wonder".
(Gilbert and Faber, 1996.):
There has long been an appreciation that wonder is an experience between humans and
the world which can engender proper thought and action. It is a totally and typically
human experience. Plato said that ‘philosophy begins in wonder,’ and his embryologist
student Aristotle concurred that ‘it is owing to wonder that people philosophize and
wonder remains the beginning of philosophy.’ At the beginnings of modern science,
Francis Bacon reaffirmed wonder as ‘the seed of knowledge.’
Bur wonder has a short half-life. It decays rapidly into awe and curiosity, two potent
but less immediate products. According to the Jewish philosopher A. J. Heschel,
‘Knowledge is fostered by curiosity; wisdom is fostered by awe.’ So wisdom and
knowledge, faith and reason are cousins whose genealogies both trace back to wonder.
According to this view, science and religion are both supported by the ability to wonder;
and both will be diminished in a world whose sources of wonder are being removed.