PERSPECTIVES
axonal outgrowth and neuronal regenera-
tion via their interaction with myelin-associ-
ated inhibitors (11). That PirB appears to be
responsible for only 50% of the binding of Aβ
to neurons in culture echoes similar observa-
tions made with PrPC (12) and suggests that
other receptors also play a role in mediating
Aβ neurotoxicity effects. Finally, engage-
ment of this neuroimmune receptor might
play a role in hypothetical immunological
aspects of Aβ-mediated toxicity.
The plethora of Aβ receptors now iden-
tified has not yet resolved a nagging ques-
tion in the field: What features characterize a
canonical Aβ receptor? The crucial issue in
this debate is the lack of definition of what is
called “toxic” Aβ (1). Aβ preparations used
for receptor discovery are typically gener-
ated by incubating monomeric Aβ peptides
in buffer solutions. This results in hetero-
geneous mixes of monomers and various
aggregates that are in dynamic equilibrium
with each other. There is some evidence
that more stable intermediates with specific
conformations are formed, but it is unclear
how these complex mixtures behave, and
EARTH SCIENCE
Causes of the Cambrian Explosion
M. Paul Smith1 and David A. T. Harper 2
M
any hypotheses have been invoked
to explain the rapid diversifi-
cation of animal species in the
early Cambrian (541million to 515 million
years ago), ranging from starbursts in the
Milky Way to intrinsic genomic reorganiza-
tion and developmental patterning. Recent
hypotheses for the Cambrian explosion fall
into three main categories: developmental/
genetic, ecologic, and abiotic/environmen-
tal, with geochemical hypotheses forming
an abundant and distinctive subset of the
last (1). Most of these hypotheses have been
posited as stand-alone processes that were
the main cause of the explosion, yet many
of them are tightly interlinked and codepen-
dent. The rapid diversification of animals in
the early Cambrian is likely to have been the
result of a complex interplay of biotic and
abiotic processes (see the first figure).
One challenge relates to the precise defi-
nition of the explosion. Is it the first appear-
1
Oxford University Museum of Natural History, Parks
Road, Oxford OX1 3PW, UK. 2Department of Earth
Sciences, Durham University, Durham DH1 3LE, UK.
E-mail: paul.smith@oum.ox.ac.uk
www.sciencemag.org SCIENCE VOL 341 20 SEPTEMBER 2013
their standardization and fine structural
characterization is lacking (1, 13). Most
of the identified Aβ receptors seem to pre-
fer oligomeric forms of Aβ, but it is as yet
unclear what these oligomeric species look
like, or whether all identified receptors bind
to the same oligomers. Finally, and perhaps
most important, the structural basis of the
Aβ oligomer–receptor interaction remains
poorly characterized. Do the numerous “Aβ
receptors” simply reflect the “sticky” nature
of Aβ oligomeric species, or is there a par-
ticular “pathological conformation” in some
of the putative oligomeric intermediates that
promotes interaction with specific recep-
tors? For instance, FcγRIIb has a preference
for Aβ42 over Aβ40 oligomers, and the flex-
ible N terminus in Aβ42 is important for its
binding to FcγRIIb and for toxicity (10).
Even though PirB is a good candidate
for pursuing the basis of Aβ neurotoxicity,
the field must also get to grips with what is
meant by “toxic” Aβ oligomers. Exchange
of Aβ preparations and careful compari-
son of data across different laboratories
is required (1, 13). Of course, as has been
ance of animal groups, their diversification,
the emergence of marine ecosystems with
“modern” trophic structures, or all of these?
The timing of the diversification of animal
groups is now fairly well known, allowing
a clear distinction to be made between the
first appearances of high-level animal crown
groups in the Neoproterozoic (1000 million to
541 million years ago), followed by the main
diversification of animal groups, a substantial
increase in morphological disparity, and the
emergence of complex food webs in the early
Cambrian (2–4). Molecular clock estimates
predict that the earliest members of many
animal groups, including sponges, cnidar-
ians, and bilaterians, lived 850 million to 635
million years ago. Yet molecular clocks and
the fossil record together indicate that more
than 100 extant animal phyla and classes first
appeared in the Cambrian; only a handful pre-
date the start of the Cambrian. Two events are
thus distinguishable, with the origin of high-
level animal groups temporally distant to
the abrupt increase in diversity and disparity
within the Cambrian—the Cambrian explo-
sion in the strict sense (see the second figure).
Published by AAAS
noted elsewhere (14), the key question is not
so much whether sticky Aβ oligomers bind
a particular receptor, but whether such Aβ
receptor–mediated pathways are function-
ally meaningful and can ultimately be used
to create novel therapies.
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Acknowledgments: B.D.S. is a consultant for Janssen Phar-
maceutica, EnVivo Pharmaceuticals, and Remynd NV.
10.1126/science.1244166
The rapid diversification of animal species
in the early Cambrian was the result of a range
of interacting biotic and abiotic processes.
One essential component of the Cambrian
explosion is the advent of bilaterian develop-
mental systems. Bilaterians are animals with
a longitudinal plane of symmetry and spe-
cialized internal organ systems, and include
most living animals with the notable excep-
tions of sponges, cnidarians, and some minor
groups. It has been argued that the origin of
the bilaterian gut and the ability to feed on
large prey items (macrophagy) around 650
million years ago in turn enabled the evo-
lution of large body sizes and skeletons in
response to seabed predation pressures (5).
This ignores, however, an apparent >100-
million-year gap between the evolutionary
innovation and its consequences. Develop-
mental systems must have been in place to
enable the macroevolutionary cascade, but
the clues for the causes of the Cambrian diver-
sification must lie closer to 540 million years.
By then, stem bilaterians had already evolved
the developmental tool kit to exploit the com-
plex mosaic of opportunities that arose (6).
With macrophagy in place, the emer-
gence of complex food webs was a crucial
driver for diversity increase in the Cambrian
1355
 PERSPECTIVES

explosion (1, 7), partly because

of the tendency of burrowing Regolith
organisms to modify the physi- erosion
cochemical properties of their
substrates (ecosystem engineer- Epicontinental sea Ca2+ PO43⫺
ing) (8). In addition, it has been Continental
argued that the inherent “evolv- flooding Cell toxicity
ability” of bilaterian animals and Sea-level rise Increase in
their tendency to induce escala- Origin of nutrient flux
biomineralization
tory arms races may account for
much extant diversity (7). These Increase in
habitable volume Genome patterning
types of feedback are manifest in
the origins of planktic and free-
swimming animals, burrowing,
Explosion in
and biomineralization, which Continental shelf animal diversity
initially were new evolution-
ary products but rapidly became Origin of Food web

Downloaded from http://science.sciencemag.org/ on January 25, 2017

entrained in the diversification. burrowing complexity
In the case of biomineraliza-
tion, the presence of feedback Substrate Origin of
loops is evidenced by the near- oxygenation plankton/nekton
simultaneous appearance of both
predatory and defensive hard tis- Interconnected causes. Earth system, developmental, and ecological processes have been hypothesized as isolated, sin-
sues across a wide range of ani- gular causes of the major diversification of marine taxa early in the Cambrian. Instead, many of these processes sit within
mal groups (9, 10). These hard a series of cascading and nested feedback loops that together generated the Cambrian explosion. Each box corresponds
tissues mainly consist of two broadly to a stand-alone hypothesis or suite of related hypotheses (red, geological; blue, geochemical; green, biological).
types of calcium biomineral, The figure represents a narrow interval of time at the beginning of the Cambrian (541 million to 521 million years ago).
suggesting that the availabil-
ity of calcium is an important aspect of the Cambrian explosion, with many of the indi- and the depth to which light penetrates, pro-
event. It has been argued that the emergence vidual hypotheses instead acting as compo- viding a further driver for large increases in
of complex food webs is the result of cross- nents of interacting feedback loops between diversity. These early events then segue into
ing a threshold or tipping point (7), but it may Earth systems and biological processes. the complex interaction of abiotic and biotic
have been an end product of complex feed- Together, these interacting processes processes shown in the first figure. It would
back loops (see the first figure). generated an evolutionary cascade that led be valuable, therefore, to model the diver-
Recently, attention has returned to abi- to the rapid rise in diversity. The initiating sification in a holistic and interdisciplin-
otic processes as a possible cause of the event is likely to have been the early Cam- ary way, rather than focusing on individual
Cambrian explosion. A long period of Neo- brian sea-level rise that led to inundation of causal factors. A substantial challenge then
proterozoic erosion had resulted in very continental margins and interiors and the lies in determining the relative position of
low-relief continental interiors with highly rapid input of erosional by-products (11). each component process upstream or down-
weathered crystalline basement rock at the This sea-level rise would also have gener- stream in the cascade of events that pro-
surface, together with associated soils (rego- ated a very large increase in habitable area duced the Cambrian explosion.
lith). Major sea-level rise in the early, but lying between the base of wave turbulence
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rock and regolith and the rapid input of cal- lage, CO, 2013).
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cium (11), phosphate (12, 13), and other 4. C. J. Lowe, Science 340, 1170 (2013).
Millions of years

Cambrian

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Ediacaran

may have directly facilitated the origin of 8. R. H. T. Callow, M. D. Brasier, Earth Sci. Rev. 96, 207
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Each hypothesis outlined here is a via-
12. P. J. Cook, J. H. Shergold, Nature 308, 231 (1984).
ble mechanism for increasing mean spe- Times of change. The major diversification of 13. M. D. Brasier, R. H. T. Callow, Mem. Ass. Austral. Palaeon-
cies diversity within habitat, differentiation marine taxa at high taxonomic levels between 635 tol. 34, 377 (2007).
between habitats, and/or total regional bio- and 443 million years ago [after (2)]. The red box 14. S. T. Brennan, T. K. Lowenstein, J. Horita, Geology 32, 473
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diversity. However, it is unlikely that any indicates the time interval discussed in the text. EB,
single casual mechanism can explain the Ediacaran biota. 10.1126/science.1239450

1356 20 SEPTEMBER 2013 VOL 341 SCIENCE www.sciencemag.org

Published by AAAS
 Causes of the Cambrian Explosion
M. Paul Smith and David A. T. Harper (September 19, 2013)
Science 341 (6152), 1355-1356. [doi: 10.1126/science.1239450]

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