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Carroll, S. B. - 2001 - Chance and Necessity. The Evolution of Morphological Complexity and Diversity PDF
Carroll, S. B. - 2001 - Chance and Necessity. The Evolution of Morphological Complexity and Diversity PDF
The primary foundation for contemplating the possible forms of life elsewhere in the Universe is the
evolutionary trends that have marked life on Earth. For its first three billion years, life on Earth was a world of
microscopic forms, rarely achieving a size greater than a millimetre or a complexity beyond two or three cell
types. But in the past 600 million years, the evolution of much larger and more complex organisms has
transformed the biosphere. Despite their disparate forms and physiologies, the evolution and diversification of
plants, animals, fungi and other macroforms has followed similar global trends. One of the most important
features underlying evolutionary increases in animal and plant size, complexity and diversity has been their
modular construction from reiterated parts. Although simple filamentous and spherical forms may evolve
wherever cellular life exists, the evolution of motile, modular mega-organisms might not be a universal pattern.
Drawn out of the realm of pure chance, the accident enters into that of necessity, of the most implacable certainties.
J. Monod1
I
t is widely accepted that the evolution of any anatomical complexity. Increases in morphological complex-
particular organism or form is a product of the ity may lead to expansions into previously unoccupied
interplay of a great number of historical ecospace and accompanying expansions of species diversity.
contingencies1. Rewind and replay the tape of life Testing these relationships, searching for trends, and
again and again, as the now familiar argument goes, identifying potential causes requires analyses far beyond the
and there is no predicting (or reproducing) the outcomes. mere description of the global history from bacteria to whales,
Roses and redwoods, humans and hummingbirds, trilobites to the consideration of detailed histories of specific lineages.
and dinosaurs each owe their existence (or demise) to Singularities are dangerous territory for the formulation of
unfathomable combinations of innumerable rolls of the general trends and principles12; fortunately, however, aspects
ecological and genetic dice. of evolutionary history have been repeated in different
Lifes contingent history could be viewed as an argument lineages. Here, I will focus on events that have occurred and
against any direction or pattern in the course of evolution or trends that are manifest in a variety of macroforms with the
the shape of life. But it is obvious that larger and more com- aim of identifying some of the trends and potential underlying
plex life forms have evolved from simple unicellular ancestors forces that have shaped the size, complexity and diversity of
and that various innovations were necessary for the evolution macroscopic life. I will first review the evidence for global
of new means of living. This raises the possibility that there trends and then consider the histories of particular lineages
are trends within evolutionary history that might reflect the where the mechanisms underlying the generation of morpho-
existence of general principles governing the evolution of logical complexity and the evolution of diversity are begin-
increasingly larger and more complex forms. The first task of ning to be better understood. In particular, I will focus on the
this review is to examine the degree to which the evolution of relationship between genomic and organismal complexity
the shapes of life are a matter of chance a random walk in that can now be addressed by recent advances in the analysis of
morphospace or of necessity borne from the demands genes, genomes and development. I will develop the argument
of natural selection and the constraints imposed by physics, that one of the most important features that has facilitated the
genetics and development. The second task is to extrapolate evolution of plant and animal complexity and diversity is the
from the evolutionary trends on Earth to assess what they modularity of their construction from reiterated, differentiat-
might portend for the evolution of life elsewhere. ed parts. Finally, I will discuss which trends in the evolution of
There is a long history of support for the general notion of morphology are likely to apply wherever life may be found.
overall evolutionary trends towards increases in size2,
complexity2,3 and diversity46. However, there are two funda- Milestones in morphological evolution
mentally distinct mechanisms that have been proposed to The principal events of interest here are the major changes in
explain these trends7. One is a random, passive tendency to organismal size, form and complexity, and the major expan-
evolve away from the initial minima of organismal size8, sions in diversity, that have produced the many shapes of
complexity and diversity through an overall increase in macroscopic life. The foundations for inferences about the
variance (that is, there is nowhere to go but up9)10. The sequence and direction of evolution are the fossil record and
second is a non-random, active or driven process that the phylogenetic tree of life. Integration of palaeontological
biases evolution towards increased size or complexity11. and systematic data is required to establish the number of
There are relationships between size and complexity and times particular events occurred, the order in which impor-
between complexity and diversity that are intuitive. Increases tant sets of traits evolved, and to identify the possible sister
in organismal size through increases in cell number create the groups of major taxonomic groups. The fossil record is also a
potential for increases in diversity of cell type and, as a result, primary source of data on the time of origin of taxa. One must
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Mammals
Flowering
CENOZOIC
earliest records of particular groups and Quaternary 1.8
plants
the radiations of selected taxa are
shown. There is earlier biomarker Tertiary 65.0
evidence for eukaryotes around 2,700
Myr (ref. 91). For sources, see text.
Cretaceous 144
MESOZOIC
Jurassic 206
Triassic 251
Insects
Permian 290
Carboniferous 354
Aquatic arthropods
(365)Tetrapods
PALAEOZOIC
Devonian 409
(428) Cooksonia
Bilaterians
Silurian 439 (458) First land plants
Multicellular
Ordovician 490
algae
Cambrian 543
(575-543) Ediacarans
(Sub-eras) (610) Oldest radially symmetric impressions (animals)
Late Proterozoic (750) Green algae
PROTEROZOIC
900
(1,000-900) Multicellular algae radiation
Middle Proterozoic
(1,200) Multicellular red algae
1,600
Early Proterozoic (1,900-1,700) Earliest eukaryotes
(2,000) Cyanobacteria
2,500
ARCHAEAN
bear in mind that initial appearances in the fossil record set only a Size and multicellularity
minimum for the age of clades. Many of the most challenging and con- For the first 2,500 million years of life on Earth, most species rarely
troversial questions in evolutionary history concern the origin of major exceeded 1 mm in size and were generally much smaller. The earliest
clades (for example, multicellular eukaryotes, animals, land plants, reported bacterial microfossils from about 3,500 million years (Myr)
insects and flowering plants), which are also a focus of this review. averaged about 5 mm in diameter14. Early eukaryotic microfossils
The initial appearances and major radiations of selected taxa (acritarchs), while considerably larger, still ranged generally from
documented in the fossil record are summarized in Fig. 1. When about 40 to 200 mm in size (with a few larger exceptions, see ref. 15) for
considered in the light of the phylogenetic relationships of the major much of their first 600800-Myr history15. Organismal size increased
multicellular taxa (Fig. 2), there are three trends evident in the fossil appreciably with the evolution of multicellular forms. In bacterial
record that I will examine in greater detail. First, multicellularity and algal forms with cell walls, one of the simplest ways to become
evolved independently many times and in all three domains of multicellular was for the products of cell division to remain together to
life2,13. Second, following the evolution of multicellularity from form long filaments13. Many early multicellular eukaryotes were
different unicellular ancestors, macroscopic forms with new body millimetre-scale, linear or branched, filamentous forms15,16.
plans or physiologies and representing higher grades of morpholog- The size and shape of life did not expand appreciably until the late
ical complexity (for example, multicellular protists, animals and Proterozoic (Fig. 1). Radially symmetric impressions and trace
land plants) arose. And third, the emergence of new forms was often fossils indicate the presence of millimetre-scale metazoans around
followed (after sometimes considerable delays) by periods of rapid 550 Myr (ref. 17; reviewed in ref. 18). The enigmatic Ediacaran fauna
diversification (for example, the Cambrian explosion of animals, comprised of tubular, frond-like, radially symmetric forms
the rise of insects in the Devonian and Carboniferous, the radiation generally reached several centimetres in size (although some, such as
of flowering plants in the late Cretaceous, and the mammalian Dickinsonia, approached 1 m), as did macroscopic algae. Organismal
radiation in the early Tertiary; Fig. 1). I shall analyse these global sizes expanded considerably in the Cambrian, including bilaterians
trends in the evolution of size, complexity and diversity in more up to 50 cm in size, as well as sponges and algae up to 510 cm
detail and then consider some potential explanations. (ref. 19). Maximal body lengths of animals increased subsequently
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BACTERIA Ciliates
Methanosarcina Cellular Fungi
slime
molds Red
Actinomycetes
Cyanobacteria algae
Myxomycetes
Myxobacteria Foraminifera
by another two orders of magnitude, as did algal sizes (for ancestors, multicellular forms have evolved many times in different
example, kelp). lineages (Fig. 2). Thus, there have been both global (for example,
The largest extant organisms, giant fungi and trees, evolved from bacteria to vertebrates) and within-lineage (for example, animals and
independent small ancestors. Land plants are believed to have the green algae/plant clade) increases in the number of cell types. But the
evolved from charophyte green algae, and both green algae and plants maximum number of cell types in general plateaus in bacteria (at 3), in
evolved from a unicellular flagellate ancestor2022. Fossil spores protists (about 4), in protostomes (about 50), and perhaps in
indicating the earliest evidence of plant life date from the mid- vertebrates as well (there is strong suspicion that cell-type number is
Ordovician. The oldest plant-body fossil (Cooksonia) suggests that underestimated in vertebrates but also better studied in these animals).
early land plants were small20,21 and, on the basis of molecular phylo- Increases in cell-type number obviously increase the potential
genetic analyses, are believed to be comparable in organization and physiological and anatomical complexity of organisms through a divi-
life cycle to liverworts23. Many of the principal groups of land plants sion of labour among cells and the formation of specialized tissues and
have evolved large (>10 m) species at some point in their history. organs. Among the bacteria, for example, large cyanobacteria (blue-
Thus, increases in both mean and maximal organismal size occurred green algae) have evolved specialized heterocysts that differentiate at
in the evolution of multicellular bacteria, eukaryotes and multicellular regular intervals within a filamentous chain. These heterocysts enable
eukaryotes, and within the algal, fungal, plant and animal lineages. cyanobacteria to segregate the processes of nitrogen fixation (in
heterocysts) from photosynthesis (in surrounding vegetative cells)2.
Complexity Spore-forming bacteria are also prokaryotic forms that generate more
Complexity is one of those problematic terms that has been used to than one cell type. There are clear advantages to the evolution of hardy
describe so many objects and phenomena as to have lost any generally spores whose production is under the influence of environmental cues.
recognized precision or meaning. In describing organisms, two of the The shapes of forms with few cells types, from bacteria to slime moulds,
most common usages are in reference to the number of different cell are limited generally to filamentous or spherical morphologies. There
types2,13,24 or the number or functional specialization of parts. is little internal morphology in organisms before the evolution of
McShea3 has suggested four distinct categories of complexity that plants, fungi and animals. The evolution of internal complexity
include the specific case of cell-type number but can be used to accompanied the evolution of greater numbers of cell types and the
describe compositions and processes at different levels of biological organization of cells into tissues and organs.
organization, from molecular to ecological organization. Specifically, The evolution of cell-type number and internal complexity has been
these four types of complexity include: (1) the number of different addressed most frequently in the Metazoa, within which the different
physical parts (for example, genes, cells, organs or organisms) in a grades of cellular and anatomical complexity are readily apparent.
system; (2) the number of different interactions among these parts; Placozoans bear only four cell types while the Porifera (sponges) and
(3) the number of levels in a causal specification hierarchy; and (4) the Cnidaria (including jellyfish and sea anemones) possess 1012 (ref. 24).
number of parts or interactions at a given spatial or temporal scale. Furthermore, cnidarians have only two distinct germ layers (that is, they
These definitions are particularly appropriate in two aspects. First, are diploblastic), whereas bilaterians possess a third, mesodermal
they allow one to frame questions about the evolution of complexity germ layer and considerably more cell types. The evolution of the
more narrowly and specifically. Second, they enable the complexity of mesoderm and its derivatives had profound consequences for the
two independent variables to be compared in order to search for or to evolution of animal body cavities, locomotion and overall size. Among
refute correlations. For example, it is becoming possible to make the bilaterians, vertebrates possess the greatest number of cell types,
comparisons of morphological complexity with the complexity of the some of which can be attributed to the evolution of the neural crest25.
genetic systems and developmental programs that generate it. Another potential index of complexity is gene number. The number
In each sense of these criteria, the evolution of life has ascended of biochemical events within a cell can increase with and therefore bear
increased grades of complexity. This is most obvious from simple some correlation to gene number. However, the relationship between
measures of cell number and type (Table 1)2,24. From unicellular gene number and the number of different cell types in multicellular
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caused marked reductions in the diversity of the global biota in many
Figure 3 episodes of lifes history. Furthermore, the dynamics of species diversifi-
600
Patterns of cation and extinction are well studied only for a few groups that have left
Insects
diversification. a long and rich fossil record. For many organisms, particularly those
Terrestrial
Number of families
Terrestrial tetrapods made entirely of soft tissues or of small size, we just cannot say whether
400
tetrapods (blue total diversity increased or decreased over long periods of time.
line) and insects What we can say is that there are many episodes in the fossil record
(green line) of bursts of diversification within lineages. Eukaryotes in the
underwent 200 Proterozoic and early Cambrian27, animals in the Cambrian28,29,
exponential insects in the Carboniferous, flowering plants in the Tertiary, and
phases of other groups experienced periods of rapid radiation (Fig. 1). The
diversification geological and ecological settings and the potential catalysts of these
over periods of 0 periods of accelerated change differ immensely in their particulars.
S D Crb P Tr Jur Cret Tert
100 Myr or more. Perhaps one general theme is that many of these radiations reflect the
400 200 0
(Adapted from release from or the surmounting of some environmental or structural
Geological time (Myr)
ref. 30.) constraint(s), or a new way of life. The most obvious of these changes is
the transition from an aquatic to a gaseous environment. The invasions
of the land by plants and animals were accomplished by enormous
organisms, if any, is not well understood. Recent inventories of the changes in physiology and anatomy, which enabled exploitation of new
complete genomes of model organisms used for studies of gene ecospace. The subsequent radiations of land plants, terrestrial
regulation, cell differentiation and development offer the opportunity tetrapods and insects were explosive and their diversifications followed
to search for correlations between gene number and cell-type number largely exponential patterns for 100 Myr or longer (Fig. 3)30.
as indices of complexity.
Among unicellular organisms, total gene numbers range from as Passive or active global trends?
few as 470 genes in Mycoplasma genitalium to more than 4,000 in There are two central questions when evaluating long-term trends
Escherichia coli (Table 1). There is no apparent relationship between in evolution. The first is whether the trend is passive (that is, due to
gene number and phylogeny among unicellular organisms. Two the increase in the total variance in a clade, with the direction of
members of the Archaea have gene numbers in the middle range of change imposed by the boundary of some initial minimum value),
unicellular genomes, as do various bacteria. The smallest genomes are or active (that is, due to the biased replacement of primitive forms
thought to derive from larger genomes through gene loss. with more derived forms). The plot of change in morphology over
Gene number is not greater in the spore-forming bacterium Bacillus time distinguishes these two trends (Fig. 4a, b). Given the initial
subtilis than in other bacteria lacking cell differentiation. However, gene conditions of life (that is, a low minimum boundary), and that sim-
number is considerably greater in the yeast Saccharomyces cerevisiae ple, small unicellular forms have not been replaced, the global
(about 50% greater than the bacterial maximum), which is capable of trends in organismal size, complexity and diversity described above
forming three different cell types (two haploid forms and one diploid must at least in part be passive and due to an overall increase in
form). In the plant Arabidopsis thaliana and in two protostomes, the variance (Fig. 4a). However, the evolution of new traits (such as
fruitfly Drosophila. melanogaster and the nematode Caenorhabditis multicellularity, cell differentiation, internal complexity, support
elegans, gene number is 24 times greater than in S. cerevisiae. And in structures and modularity) can establish new levels of complexity
vertebrates, gene number is estimated to be on the order of 46 times and enable subsequent bursts of diversification (through further
greater than in the two reported protostome genomes. increases in variance). Thus, whereas global trends may be passive,
From these surveys, we can readily conclude that gene number and there may be active, directional trends nested within the overall arc
cell-type number have increased in the evolution of macroscopic forms of evolutionary history4. To identify these active trends and to
from unicellular ancestors. However, the quantitative relationship consider how they have influenced the shapes of life, we have to look
between the two indices is not at all clear. Gene number varies more than at the histories of individual clades.
eightfold among unicellular organisms. Although multicellular The second question in evaluating long-term evolutionary trends,
eukaryotes uniformly possess more genes than bacteria or achaea, active or passive, concerns whether the mechanism involved is exter-
organisms with fewer cell types may possess more genes (for example, nal (affected by selection, ecology or environment) or internal (under
A. thaliana compared with D. melanogaster) and the reasons for genetic, developmental or biomechanical control). It is important to
differences in gene number between species of similar cell-type com- note that the distinction between active and passive trends bears on
plexity (for example, C. elegans compared with D. melanogaster) are the question of the potential mechanisms responsible, not on the exis-
unknown. C. elegansand D. melanogaster belong to the same major pro- tence of a trend. Passive trends may well have interesting origins10. For
tostome clade, the Ecdysozoa, and it is known from analysis of principal example, the tendency for mammals to evolve at small sizes (Copes
developmental genes that the nematode has lost genes that were present rule, see below) begs explanation.
in its common ancestors26. In spite of this, the total gene number in C.
elegans exceeds that of D. melanogaster by 5,000 genes. One important Active trends within clades
contribution to the differences in gene content is the extent and pattern Most empirical work on evolutionary trends within clades has focused
of gene duplications and losses. These events are lineage-specific so the on animals because of their richer fossil record. Considerable emphasis
sampling of a few species chosen for reasons other than their phyloge- has been placed upon methodology because different approaches may
netic relevance may obscure a relationship, if any, between gene number yield different conclusions regarding the same phenomenon. Three
and morphological complexity. However, while total gene number may tests have been devised to distinguish passive from active increases: (1)
not be all that informative in regard to complexity, the number of genes the test of the behaviour of the minimum, which should increase if the
with particular developmental functions may be relevant. system is driven; (2) the ancestor-descendent pair test, which should
reveal increases in random samples of ancestor-descendent pairs that
Diversity are selected away from the boundary of the minimum; and (3) the
It is a given that lifes diversity has expanded from its origin. The more subclade test, which should reveal a skew in the mean of subclades
pertinent question is whether this expansion represents a continuous sampled from the tail of a distribution7. These tests have revealed
increase? The answer is most definitely no. Major extinctions have some active trends in the evolution of animal size and complexity.
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The evolution of size and Copes rule
One of the most scrutinized trends is that noted by E. D. Cope31 Passive trend Active trend
regarding the size increase in mammalian fauna during the Cenozoic
(65 Myrpresent). Cope attributed the pattern to a tendency for new
lineages to evolve at small sizes and an active drive towards increasing
size. An active drive has been attributed to various advantages of
larger size (for example, evasion of predators, increased brain size or
increased longevity; see ref. 8), but rigorous evidence for such a trend
was lacking. Stanley8 attributed Copes rule to be due to the tendency
for new groups to evolve at small size (that is, an initial minimum
value) relative to their optima such that there is a passive drift towards
larger mean body size in descendants through an increase in variance.
However, Alroy32, in an analysis of body mass estimates for over 1,500
North American fossil mammal species, found a consistent increase
between matched pairs of younger and older species. Similarly,
MacFadden33 found a driven trend in the evolution of body size of
horses within this era. These within-lineage comparisons indicate
that active trends do operate within overall passive trends.
Time
Time
A general applicability of Copes rule to other taxa and eras has not
been found. Neither Cretaceous molluscs34 nor planktonic
foraminifera10 show an active trend. Rather, trends of increasing size in
both of these taxa have been attributed to an overall increase in variance.
Carboniferous
5 For an illustration of the relationship between the evolution of
modular body plans, complexity, diversity and the architecture of the
underlying genetic systems that differentiate forms, we can return to the
10
example of the evolution of arthropod limb-pair types (Fig. 5). Cisne40
Late Permian
5
documented a trend of an increasing mean and maximum number of
limb-pair types in the first half of the Phanerozoic. The functional sig-
nificance of this potentially driven trend is obvious. Arthropod limbs
15 are the tools of its trade40 and the morphological specialization of
Recent limbs for feeding, locomotion, sensation, copulation, brooding young,
10 burrowing and defence is reflected in the variety of limb types (that is,
complexity). The most specialized orders, those with the greatest
5 number of different limb types, are also the most diverse in terms of the
number of species. This is illustrated by the malacostracan crustacean
lineage that evolved filtering maxilla as a new means of feeding. The
1 2 3 evolution of maxillopeds freed the serially similar pairs of trunk limbs
Tagmosis value
to become specialized for walking, swimming and burrowing40.
The diversification of the modular arthropod body plan and of
Figure 5 The evolution of limb-type complexity in aquatic arthropods. The number of arthropod limb types required the diversification of the genetic
orders is plotted against tagmosis, a value computed by considering both the total regulatory system that specifies regional and segmental identities in
number and different types of arthropod limbs. The minimum, mean, and maximum arthropods, namely, the Hox genes. The products of the Hox genes are
tagmosis value increased from the Cambrian to the late Permian, suggesting an active expressed in domains that subdivide the anteriorposterior axis of
trend. (Adapted from ref. 37.) bilaterians, and these proteins regulate the expression of many genes
within these domains58. The differentiation of serially homologous
limbs in arthropods is regulated by different Hox genes expressed in
limitations, such increases in complexity may allow the exploitation different developing limb primordia (reviewed in refs 16, 55 and 59).
of new morphospace and ecospace4,46. In the case of skeletons Comparisons of representatives of all arthropod classes and many
described above, the evolution of the biochemistry for forming hard different orders have revealed strong correlations between the regional
parts (chitinous cuticles and mineralized internal or external deployment of Hox genes and the patterns of limb differentiation
elements) opened up new ways of life that enabled bursts of (reviewed in refs. 16, 55 and 60). Thus, in taxa with similar sets of
diversification. This theme appears repeatedly in evolutionary repeating limbs (for example, centipedes and brachiopod crustaceans),
history. The invasion of the land by plants, tetrapods and insects the same Hox genes or combination of Hox genes are expressed in all of
triggered radiations that transformed terrestrial ecosystems. The the limbs of the same type. Whereas in taxa with different numbers
early phase of diversification of these groups (considering higher and kinds of limbs, relative shifts in Hox-gene expression domains are
taxonomic levels) was greater than that of later phases, until correlated with differences in limb number and identity.
later innovations (for example, flight in vertebrates or flowers in Arthropod limb-type diversity has evolved from ancestors with very
plants) led to further bursts of diversification. Once again, the similar complements of Hox genes61. This is contrary to initial expecta-
overall trends seem to be passive (and those at higher taxonomic tions that gene duplication and divergence would correlate with the
levels are to some degree the consequence of how the topology of duplication and increasing diversity of arthropod segment and limb
evolutionary trees are determined47,48), but that does not at all types62,63. Instead, it is apparent that the great diversification of limb
diminish the importance of mechanisms underlying the increases in types is due to the evolution of regulatory mechanisms operating at two
complexity or diversity in these lineages, the most complex and major hierarchical levels in arthropod development. First, at the level of
diverse of all macroscopic forms. the regulation of Hox genes along the anteriorposterior axis; and
Can we draw any generalities about deeper mechanisms underlying second, within the Hox-regulated hierarchies of genes that pattern
these overall trends, perhaps even the active trends that may be nested individual limbs. The evolution of axial diversity within the modular
within them? I argue here that one of the most critical features underly- body plans of other bilaterian phyla such as annelids and vertebrates
ing the evolution of large and complex animals and plants, and a key to has followed similar themes (reviewed in ref. 55).
their diversity, is their modular construction. The significance of the
construction of animals from repeated parts has long been recognized. Modularity, constraints and evolvability
Cope31, Bateson49, Gregory50, Rensch51, Bonner2, as well as Darwin (see These recent discoveries in developmental genetics and comparative
ref. 52) have suggested various advantages of modular construction, biology illustrate an important property bestowed upon evolving
including the facilitation of greater size and efficiency, and the organisms by modularity, that is, the ability to dissociate develop-
evolution of greater complexity and adaptation through the functional mental processes in one part of the body from another64,65. The
differentiation of repeated parts. Similarly, in plants, modular con- regional specification systems that subdivide developing animal and
struction allows for greater size and the differentiation of functional plant embryos into discrete territories make it possible for the devel-
roles among leaf and reproductive structures53. Modularity in plants opment and morphology of one territory to evolve independently of
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Table 1 Evolution of cell type and gene number complexity. Interestingly, protostomes and more basal deuterostomes
Number of Species Number of genes Reference possess similar complements of regulators that control cell-type, tissue
cell-types* in genome and regional identities.
1 Mycoplasma genitalium 470 76 Expansions in the number of regulatory proteins offer the poten-
Rickettsia prowazekii (intracellular 834 77
parasite) tial, but are not necessary for, the evolution of increased complexity
Haemophilus influenzae 1,709 78 and the expansion of diversity. The evolutionary trends in arthropod
Escherichia coli 4,288 79 and vertebrate axial complexity and diversity are due to the evolution
Campylobacter jejuni 1,654 80
Aquifex aeolicus (thermophile) 1,512 81 of genomic complexity at a different level than gene number, that is, at
Neisseria meningitidis 2,121 82 the level of the evolution of the regulatory elements that act in cis to
Archaeoglobus fulgidus (Archaea) 2,436 83
Methanococcus jannaschii (Archaea) 1,738 84
control gene expression. Within these phyla, no substantial increase in
Synechocystis sp. (cyanobacterium) 3,168 85 the number of genes involved in regional specification occurred.
2 Bacillus subtilis ~4,100 86 Rather, the evolution of advanced forms with greater numbers of dif-
Caulobacter crescentus ferentiated serial structures has occurred through an expansion in the
3 Saccharomyces cerevisiae 6,241 87 number of regulatory elements that control region-specific expression
4 Volvox of genes. The expansion of regulatory elements constitutes increases in
Ulva (sea lettuce) placozoans
genomic complexity in all four senses described earlier in the
7 Mushrooms
Kelp
number of different parts (regulatory elements) in a regulatory system,
~11 Sponge, cnidarians
in the number of different interactions of these parts, in the number of
~30 Arabidopsis thaliana (plant) ~24,000 88,89
levels in developmental hierarchies, and in the number of parts and
~50 Caenorhabditis elegans (nematode) 18,424 90
interactions at a given spatial scale. Regulatory evolution creates new
Drosophila melanogaster (fruitfly) 13,601 70 combinations of gene expression and therefore enables increases in the
~120 Zebrafish >80,000100,000 information content of genomes and the generative potential of
~120 Human ~80,000100,000 development without expansion of gene number. The role of regulato-
*From refs 2, 24. ry evolution is therefore key to understanding how morphological
complexity and diversity evolve in macroscopic forms.
another. It has been suggested that modularity (also called compart- Chance and necessity
mentation66,67) facilitates change by conferring upon organisms a Perhaps the most surprising conclusion one might draw from the
greater ability to escape internal constraints on morphology67. These consideration of the complexity of genes and genomes is that the
constraints include the physical limits imposed by biomechanics on generative potential of genomes is far greater than is realized in evolu-
organismal size and shape and genetic and developmental con- tion. Kauffman73 has pointed out that there is a vast difference
straints that limit the range of variation that is tolerated and available between the potential number of combinations of possible gene
within species (see ref. 64 for a discussion of constraints). If modular- expression states and those that actually exist in any organism. Given
ity and dissociation enhance the capacity to generate variation (that just two inputs into each gene, a system of 100,000 genes has 2100,000
is, evolvability), then this may confer a selective advantage on different possible states. Yet, if we use cell-type number as an indica-
modular clades that possess it66,67. Exploitation of this dissociability is tor of gene expression states, only 200300 states are realized (more
illustrated by the great variety of forms and functions seen in the states are realized in modular organisms through differential expres-
serially repeated parts of animals and plants. sion in different modules). Furthermore, given that multicellularity
seems to be readily evolved and that very few regulatory proteins can
Genomic complexity and regulatory evolution orchestrate markedly different cell physiologies, it is curious that
The generation of cell-type and body-part diversity depends upon more multicellular forms have not evolved.
transcriptional regulatory proteins that control the cell- or region- We do not understand why the actual complexity realized in
specific expression of target genes. The differences in gene expression evolution is far less than what seems to be possible genetically. The
between cell types within an organism can number in the hundreds observed limits of form seem to be due to a combination of both
to thousands, but these differences are often controlled by just a small chance and necessity, a product of historical contingency and
set of regulatory proteins. In B. subtilis for example, a small number imposed by external agents (for example, selection) and internal
of regulators control the differential expression of several hundred rules (for example, constraints). The demands of natural selection
genes during sporulation68. In the yeast S. cerevisiae, a small set of may exclude or favour certain forms, but it is widely agreed that
transcription factors orchestrates the regulation of genes involved in selection cannot be the whole story. Internally imposed constraints
cell-type differences69. In metazoans, cell-type differences (for also shape the world of possible morphologies and are themselves
example, muscle compared with neural) and body-region identity factors that can evolve74.
are regulated typically by a few proteins, whereas pattern formation
within tissues is regulated by a larger set of proteins55. Only about Are there universal rules to the shapes of life?
35% of the proteins encoded by animals genomes are transcrip- The parochial question nested within the mystery of the existence of
tional regulators70,71. Therefore, the total number of genes is not a life on other bodies is that of the existence of forms like the ones that
driver of cell type or other indices of morphological complexity. For have occurred on Earth. A few extrapolations seem to be reasonably
instance, greater gene number (for example, in C. elegans compared grounded in the overall trends of lifes history reviewed here. Assum-
to D. melanogaster, or in zebrafish compared to humans) does not ing a cellular basis of life elsewhere, the passive trends towards
dictate greater cell-type number or any other index of morphological increases in organismal size, complexity and diversity from some
complexity (indeed, C. elegans is a highly derived ecdysozoan that has initial minima are certain to prevail in any system. It must be kept in
lost certain morphological features (eyes) and Hox genes that were mind, however, that few macroscopic forms evolved in the first
present in the common ancestor it shares with Drosophila). 3 billion years of life on Earth. Therefore, the time required for any
It seems that most expansion in the genetic toolkit for bilaterian quantum change in morphology is entirely contingent upon the
development occurred in two intervals of bilaterian evolution. First, in particular history of any system. As for the shapes of life, macroscopic
the stem lineage leading to bilaterians, and later, in the evolution of forms are most likely to be multicellular and there is a finite set of
vertebrates from a chordate ancestor72. These two intervals of Hox simple geometries such as those that dominated the early history
gene expansion do correlate with the evolution of increased grades of of life on Earth (linear and branched filaments, cylinders and
1108 2001 Macmillan Magazines Ltd NATURE | VOL 409 | 22 FEBRUARY 2001 | www.nature.com
insight review articles
spheres) that are likely to satisfy the constraints imposed by 42. Budd, G. The morphology of Opabinia regalis and the reconstruction of the arthropod stem-group.
Lethaia 29, 114 (1996).
diffusion and biomechanics and that are therefore likely to be 43. Foote, M. Discordance and concordance between morphological and taxonomic diversity.
universal2,75. Paleobiology 19, 185204 (1993).
But the evolution of motile, modular mega-organisms may be a 44. Thomas, R. D. K. The skeleton space: a finite set of organic designs. Evolution 47, 341360 (1993).
45. Thomas, R. D. K., Shearman, R. M. & Stewart, G. W. Evolutionary exploitation of design options by
different story. Only after 3 billion years of physiological and anatom-
the first animals with hard skeletons. Science 288, 12391242 (2000).
ical evolution, vast changes in the environment and ecology (that 46. Stebbins, G. L. The Basis of Progressive Evolution (Univ. North Carolina Press, Chapel Hill, 1969).
were partly biogenic in nature), and extensive genetic and 47. Raup, D. M. On the early origins of major biologic groups. Paleobiology 9, 107115 (1983).
developmental innovations did such beasts emerge on Earth. And, 48. Smith, A. B. Systematics and the Fossil Record (Blackwell Scientific Publications, Oxford, 1994).
49. Bateson, W. Materials for the Study of Variation (Macmillan, London, 1894).
although some symmetrical body organization is likely of macro- 50. Gregory, W. K. Reduplication in evolution. Quart. Rev. Biol. 10, 272290 (1935).
forms75, there is no basis to assert that bilateral, radial or spiral forms 51. Rensch, B. Evolution above the Species Level (Columbia Univ. Press, New York, 1960).
were or would be inevitable. Nor, sadly, is their continued evolution 52. McShea, D. W. Complexity and evolution: what everybody knows. Biol. Philosophy 6, 303324 (1991).
assured as the ecological dice are now in the hands of a single species 53. Niklas, K. J. Plant Allometry: The Scaling of Form and Process (Univ. Chicago Press, Chicago, 1994).
54. Davidson, E., Peterson, K. & Cameron, R. Origin of bilaterian body plans: evolution of developmental
that is on a path to extinguishing a substantial fraction of all diversity regulatory mechanisms. Science 270, 13191325 (1995).
before the question of life elsewhere may be answered. 55. Carroll, S. B., Grenier, J. & Weatherbee, S. D. From DNA to Diversity: Molecular Genetics and the
Evolution of Animal Design (Blackwell, Cambridge, 2001).
1. Monod, J. Chance and Necessity (Vintage Books, New York, 1971).
56. Ma, H. & DePamphilis, C. The ABCs of floral evolution. Cell 101, 58 (2000).
2. Bonner, J. T. The Evolution of Complexity by Means of Natural Selection (Princeton Univ. Press,
57. Ambrose, B. A. et al. Molecular and genetic analyses of the silky1 gene reveal conservation in floral
Princeton, 1988).
organ specification between eudicots and monocots. Mol. Cell 5, 569579 (2000).
3. McShea, D. W. Metazoan complexity and evolution: is there a trend? Evolution 50, 477492 (1996).
58. Carroll, S. Homeotic genes and the evolution of arthropods and chordates. Nature 376, 479485 (1995).
4. Knoll, A. H. & Bambach, R. K. Directionality in the history of life: diffusion from the left wall or
59. Weatherbee, S. D. & Carroll, S. B. Selector genes and limb identity in arthropods and vertebrates. Cell
repeated scaling of the right? Paleobiology 26(Suppl.) 114 (2000).
97, 283286 (1999).
5. Gould, S. J. Full House (Harmony Books, New York, 1996).
60. Akam, M. Arthropods: developmental diversity within a (super) phylum. Proc. Natl Acad. Sci. USA
6. Foote, M. Cambrian and recent morphological disparity. Science 258, 18161818 (1992).
97, 44384441 (2000).
7. McShea, D. W. Mechanisms of large-scale evolutionary trends. Evolution 48, 17471763 (1994).
61. Grenier, J., Garber, T., Warren, R., Whitington, P. & Carroll, S. Evolution of the entire arthropod Hox gene
8. Stanley, S. M. An explanation for Copes rule. Evolution 27, 126 (1973).
set predated the origin and radiation of the onychophoran/arthropod clade. Curr. Biol. 7, 547553 (1997).
9. Maynard Smith, J. Time in evolutionary process. Studium Generale 23, 266272 (1970).
62. Lewis, E. B. A gene complex controlling segmentation in Drosophila. Nature 276, 565570 (1978).
10. Gould, S. J. Presidential Address. Trends as changes in variance: a new slant on progress and
63. Akam, M. The molecular basis for metameric pattern in the Drosophila embryo. Development 101,
directionality in evolution. J. Paleont. 62, 319329 (1988).
122 (1987).
11. Wagner, P. J. Contrasting the underlying patterns of active trends in morphological evolution.
64. Raff, R. A. The Shape of Life (Univ. Chicago Press, Chicago, 1996).
Evolution 50, 9901007 (1996).
65. Raff, R. & Sly, B. J. Modularity and dissociation in the evolution of gene expression territories in
12. Hawking, S. W. A Brief History of Time: From the Big Bang to Black Holes (Bantam Books, Toronto, 1988).
development. Evol. Dev. 2, 102113 (2000).
13. Bonner, J. T. The origins of multicellularity. Integ. Biol. 1, 2836 (1998).
66. Gerhart, J. & Kirschner, M. Cells, Embryos, and Evolution (Blackwell Science, Malden, 1997).
14. Schopf, J. W. Microfossils of the Early Archean Apex chert: new evidence of the antiquity of life.
67. Kirschner, M. & Gerhart, J. Evolvability. Proc. Natl Acad. Sci. USA 95, 84208427 (19998).
Science 260, 640645 (1993).
68. Fawcett, P., Eichenberger, P., Losick, R. & Youngman, P. The transcriptional profile of early to middle
15. Knoll, A. H. The early evolution of eukaryotes: a geological perspective. Science 256, 622627 (1992).
sporulation in Bacillus subtilis. Proc. Natl Acad. Sci. USA 97, 80638068 (2000).
16. Butterfleld, N. J. Bangiomorpha pubescens n. gen., n. sp.: implications for the evolution of sex,
69. Johnson, A. D. Molecular mechanisms of cell-type determination in yeast. Curr. Opin. Genet. Dev. 5,
multicellullarity, and the Mesoproterozoic/neoproterozoic radiation of eukaryotes. Paleobiology 26,
552558 (1998).
386404 (2000).
70. Adams, M. D. et al. The genome sequence of Drosophila melanogaster. Science 287, 21852195 (2000).
17. Martin, M. W. et al. Age of Neoproterozoic bilaterian body of trace fossils, White Sea, Russia:
71. Ruvkin, G. & Hobart, O. The taxonomy of developmental control in C. elegans. Science 282,
implications for metazoan evolution. Science 288, 841845 (2000).
20332041 (1998).
18. Knoll, A. H. & Carroll, S. B. Early animal evolution: emerging views from comparative biology and
72. Garcia-Fernandez, J. & Holland, P. W. Archetypal organization of the amphioxus Hox gene cluster.
geology. Science 284, 21292137 (1999).
Nature 370, 563566 (1994).
19. Briggs, D. E. G., Erwin, D. H. & Collier, F. J. The Fossils of the Burgess Shale (Smithsonian Institution
73. Kauffman, S. At Home in the Universe (Oxford University Press, New York, 1995).
Press, Washington DC, 1994).
74. Budd, G. E. Does evolution in body patterning genes drive morphological changeor vice versa?
20. Kenrick, P. & Crane, P.R. The Origin and Early Diversification of Land Plants (Smithsonian Institution
BioEssays 21, 326332 (1999).
Press, Washington DC, 1997).
75. Stewart, I. Lifes Other Secret (Wiley, New York, 1998).
21. Graham, L. E. Origin of Land Plants (Wiley, New York, 1993).
76. Fraser, C. M. et al. The minimal gene complement of Mycoplasma genome. Science 270, 397404 (1995).
22. Kirk, D. L. Volvox: Molecular Genetic Origins of Multicellularity and Cellular Differentiation
77. Andersson, S. G. E. et al. The genome sequence of Rickettsia prowazekii and the origin of
(Cambridge Univ. Press, Cambridge, 1998).
mitochondria. Nature 396, 133143 (1998).
23. Qui, Y.-L., Cho, Y., Cox, J. C. & Palmer, J. D. The gain of three mitochondrial introns identifies
78. Fleischmann, R. D. et al. Whole-genome random sequencing and assembly of Haemophilus influenzae
liverworts as the earliest land plants. Nature 394, 671674 (1998).
Rd. Science 269, 496412 (1995).
24. Valentine, J. W., Collins, A. G. & Meyer, C. P. Morphological complexity increase in metazoans.
79. Blattner, F. R. et al. The complete genome sequence of Escherichia coli K-12. Science 277, 14531462 (1997).
Paleobiology 20, 131142 (1994).
80. Parkhill, J. et al. The genome sequence of the food-borne pathogen Campylobacter jejuni reveals
25.Shimeld, S. M. & Holland, P. W. H. Vertebrate innovations. Proc. Natl Acad. Sci. USA 97,
hypervariable sequences. Nature 403, 665668 (2000).
44344437 (2000).
81. Deckert, G. et al. The complete genome of the hyperthermophilic bacterium Aquifex aeolicus. Nature
26. de Rosa, R. et al. Hox genes in brachiopods and priapulids and protostome evolution. Nature 399,
392, 353358 (1998).
772776 (1999).
82. Parkhill, J. et al. Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491.
27. Knoll, A. H. Proterozoic and early Cambrian protists: evidence for accelerating evolutionary tempo.
Nature 404, 502506 (2000).
Proc. Natl Acad. Sci. USA 91, 67436750 (1994).
83. Klenk, H.-P. et al. The complete genome sequence of the hyperthermophilic, suphate-reducing
28. Conway Morris, S. The Crucible of Creation: The Burgess Shale and the Rise of Animals (Oxford Univ.
archaeon Archaeoglobus fulgidus. Nature 390, 364370 (1997).
Press, Oxford, 1998).
84. Bult, C. J. Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii.
29. Budd, G. E. & Jensen, S. A critical reappraisal of the fossil record of the bilaterian phyla. Biol. Rev. 75,
Science 273, 10581073 (1996).
253295 (2000).
85. Kaneko, T. et al. Sequence analysis of the genome of the unicellular Cyanobacterium Synechocystis sp.
30. Benton. M.J. Models for the diversification of life. Trends Ecol. Evol. 12, 490495.
strain. DNA Res. 3, 109136 (1996).
31. Cope, E. D. The method of creation of organic forms. Proc. Am. Phil. Soc. 12, 229263 (1871).
86. Kunst, F. et al. The complete genome sequence of the Gram-positive bacterium Bacillus subtilis.
32. Alroy, J. Copes rule and the dynamics of body mass evolution in North American fossil mammals.
Nature 390, 249256 (1997).
Science 280, 731734 (1998).
87. Goffeau, A. et al. The yeast genome directory. Nature 387, 5105 (1997).
33. MacFadden, B. J. Fossil horses from Eohippus (Hyracoherium) to Equus: scaling, Copes law, and
88. European Union Arabidopsis Genome Sequencing Consortium & Cold Spring Harbor, Washington
the evolution of body size. Paleobiology 12, 355369 (1986).
University in St Louis and PE Biosystems Arabidopsis Sequencing Consortium. Sequence and
34. Jablonski, D. Body-size evolution in Cretaceous molluscs and the status of Copes rule. Nature 385,
analysis of chromosome 4 of the plant Arabidopsis thaliana. Nature 402, 769777 (1999).
250252 (1997).
89. Lin, X. et al. Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana. Nature 402,
35. De Robertis, E. M. & Sasai, Y. A common plan for dorsoventral patterning in Bilateria. Nature 380,
761768 (1999).
3740 (1996).
90. Rubin, G. M. et al. Comparative genomics of the eukaryotes. Science 287, 22042215 (2000).
36. De Robertis, E. M. The ancestry of segmentation. Nature 387, 2526 (1997).
91. Brocks, J. J., Logan, G. A., Buick, R. & Summons, R. E. Archean molecular fossils and the early rise of
37. Valentine, J. Late Precambrian bilaterians: grades and clades. Proc. Natl Acad. Sci. USA 91, 67516757 (1994).
eukaryotes. Science 285, 10331036 (1999).
38. Carlson, S. J. Evolutionary trends in the articulate brachiopod hinge mechanism. Paleobiology 18,
344366 (1992).
Acknowledgements
39. Saunders, W. B., Work, D. M. & Nikolaeva, S. V. Evolution of complexity in Paleozoic ammonoid
I thank A. Knoll for discussions and helpful pointers; R. Losick and A. Johnson for
structures. Science 286, 760763 (1999).
information on microbial gene regulation; G. Budd, J. Crow, N. King and J. True for
40. Cisne, J. L. Evolution of the world fauna of aquatic free-living arthropods. Evolution 28, 337366 (1974).
suggestions on the text; J. Carroll for preparation of the manuscript; and L. Olds for the
41. McShea, D. W. Evolutionary change in the morphological complexity of the mammalian vertebral
artwork. S.B.C. is an Investigator of the Howard Hughes Medical Institute.
column. Evolution 47, 730740 (1993).
NATURE | VOL 409 | 22 FEBRUARY 2001 | www.nature.com 2001 Macmillan Magazines Ltd 1109