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PLASTICITY AND ROBUSTNESS IN DEVELOPMENT AND EVOLUTION
Published by Oxford University Press on behalf of the International Epidemiological Association
ß The Author 2012; all rights reserved.
219
International Journal of Epidemiology 2012;41:219–223
doi:10.1093/ije/dyr240
Plasticity and robustness in development
and evolution
Patrick Bateson1* and Peter Gluckman2
1
Sub-Department of Animal Behaviour, University of Cambridge, Cambridge, UK and 2Centre for Human Evolution, Adaptation
and Disease, Liggins Institute, University of Auckland, Auckland, New Zealand
*Corresponding author. Sub-Department of Animal Behaviour, University of Cambridge, Cambridge, CB23 8AA, UK. E-mail:
[email protected]
Accepted
14 December 2011
Biology presents many wonders, but one of the most
remarkable is how a complex multicellular organism
grows from a single cell. Until recently, the processes
involved seemed largely beyond understanding
and, even now, much remains to be discovered.
Nevertheless, some factual certainties have been
self-evident for a long time. An egg taken from a
duck’s nest and incubated by a hen does not hatch
out as a different species from its biological mother.
Many of its characteristics were latent from the
moment its mother’s egg was fertilized by its father’s
sperm. These ‘robust’ constancies of development are
profound and real. At the same time, the hatched
duckling is capable of adapting to many challenges
posed by its environment. It can cope with disabilities
generated by accidents or disease. It can learn to
recognize particular members of its species and acquire preferences for particular foods that are available to it. The plasticity of the bird is as remarkable as
its robustness.
Likewise every human being is at once both developmentally robust and plastic. No one will confuse a
human with a rhesus monkey. At the same time,
humans possess great capacity for change, a capacity
that, as in other species, emerges from the beginning
of its development. Here, however, lies a trap. It does
not follow that two distinct processes can be cleanly
separated, one leading to an invariant outcome and
the other generating differences between individuals
due to culture, education and differences in developmental exposures and experience. If this were true, it
might be appropriate to ask the question how much
of behaviour pattern is innate and how much is learned or, more generally, how much is genetic and how
much is due to the environment. This dichotomy is
neither true nor helpful and confuses folk biology
with real biology.1
Consider the human capacity for using language.
For the vast majority of individuals, language develops with a regularity that is truly astonishing.
The categories of sounds that are detected and the
vocabulary that is used are dependent on the linguistic environment in which the child grows up. Once
adult, the particular language and dialect acquired by
an individual tends to be highly stable. Nothing is
more evident than in the ease with which young children become multilingual and yet adults struggle with
a new language. Robust rules are required for the
plasticity needed in language acquisition; the robust
outcome is dependent on the individual’s plasticity.
The interplay between different types of developmental process is obvious.
When the processes generating robustness and plasticity are examined in greater detail, they are both
found to comprise a suite of different mechanisms
acting at various levels of biological organization
from the gene to the organism.1 Many different processes are involved in generating robust outcomes and
many different forms of plasticity can be recognized.
Unfortunately, the picture is further confused by the
inconsistent use of terminology by various authorities
to describe these various mechanisms. When terms
such as canalization, stabilizing selection or genetic
assimilation are used, it is important to understand
the context in which a particular author is using such
terms. For example, although robustness has been
defined as an insensitivity or resistance of the phenotype to environmental or genetic perturbations,2 the
persistence of robust characteristics may be achieved
by redundancy, repair when a system is damaged or
by active regulation.
Plasticity is equally a term that is applied across a
broad range of biological phenomena of very different
characteristics and significance. Muscles that are not
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INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
used diminish in size and those that are exercised
become larger. These are reversible phenomena. In
many other cases, and particularly those initiated
early in development, they are not. When one
kidney fails to form, the other kidney undergoes compensatory hypertrophy and the outcome is stable.
In social insects such as the honeybee, the particular
way in which the larvae are nourished establishes
many distinct aspects of the anatomical, physiological
and behavioural aspects of the phenotype for the rest
of the life course including whether the individual
devotes her life to reproduction or to caring for the
colonial nest.3 Temperature-dependent sexual differentiation in many reptiles is a further example of irreversible developmental plasticity leading to alternate
but robust phenotypes. Nutritional and related exposures in early life affect how the organism responds to
nutritional loads later in life.4 Similarly, the behavioural repertoires of an individual can be changed
by one of the many different types of learning
and, at the molecular level, the immune system responds to infection by developing a long-lasting reaction to the specific virus or parasite that caused the
infection.
The persistence of alternative developmental tactics
based on the processes of developmental plasticity,
whether manifest as distinct polymorphisms (such
as the worker or queen bee, both of which are derived
from the diploid chromosomal female embryo) or a
continuous range of phenotypes (sometimes termed
the reaction norm5), is found throughout the animal
and plant kingdoms. Their persistence implies that
they have assisted individuals in the lineage to survive
and reproduce successfully.
Understanding of the importance of such processes
in human biology and in understanding human disease is growing rapidly. For example, the size of
unborn offspring is influenced by the nutritional
and other physiological conditions, such as parity, of
the mother.6 When the fetus responds to an adverse
environment by reducing its growth, it makes an
adaptive trade-off. It increases the likelihood of immediate survival even though the risk of a shorter life
is enhanced by being born small. Nevertheless, the
potential exists for the offspring to survive and reproduce as opposed to a greater likelihood of intrauterine
death.7
More subtle trade-offs also exist. In response to maternal cues, offspring can make subtle changes in
their physiological development in expectation of
increasing the probability of survival and reproductive
success in an anticipated later environment. Such responses are adaptive when the mother’s condition
predicts accurately the environment in which her offspring is likely to live but leads to both short-term
and long-term health and survival problems when it
does not.8 Such responses will evolve and be sustained where the capacity to predict a relatively persistent environmental change exists. The fitness
disadvantage of erroneous prediction need not be
symmetrical.9 Erroneous prediction in one direction
may have few or no consequences on reproductive
success, whereas erroneous prediction in the other
may have serious consequences. The fitness costs of
predicting a high nutrient environment and ending up
in low nutrient environment may be much greater
than the reverse.
A key question is whether these vastly heterogeneous phenomena, described as adaptive plasticity,
have anything in common with each other. Whether
or not they are necessarily or even plausibly related,
they are all of great biological significance and they
work together with each other.
Modern understanding of an individual’s development goes well beyond accepting that interactions between the organism and its environment are crucial.
The conditional character of an individual’s development and its implications for post-natal health
and survival emphasizes the need to understand
the processes of development that underlie these subsequent interactions. This is what Conrad Waddington
termed ‘epigenetics’ more than half a century ago.10
More recently, epigenetics has become narrowly and
mechanistically defined as the molecular processes by
which traits defined by a given profile of gene expression can persist across mitotic cell division, but which
do not involve changes in the nucleotide sequence of
the DNA.11 The term has come to describe those molecular mechanisms through which both dynamic and
stable changes in gene expression are achieved, and
ultimately how variations in environmental experiences can modify this regulation of DNA. Most attention in this rapidly expanding field of research
has focused on the inter-related processes of DNA
methylation at cytosine nucleotides and associated
histone modifications. These processes lead to chromatin being either more or less accessible to transcriptional regulators.12 Although much remains to
be learned about the molecular mechanisms involved,
non-coding RNAs probably play an important role in
conferring specificity to these molecular processes.13
Epigenetically mediated variation in the contextspecific expression of genes is critical in shaping individual differences in phenotype. This is not to say
that differences in the copy number or nucleotide
polymorphisms leading to altered sequences of particular genes between individuals do not contribute
to phenotypic differences, but rather that individuals
carrying identical genotypes can diverge in phenotype
if they experience separate environmental experiences
that differentially and potentially permanently alter
gene expression.14
For historical and methodological reasons, the
best-studied process of epigenetic regulation is that
of DNA methylation. Generally, enzymatic mediated
methylation occurs at DNA sequences involving the
nucleotides cytosine and guanine. These sequences
occur in clusters known as CpG islands or more
PLASTICITY AND ROBUSTNESS IN DEVELOPMENT AND EVOLUTION
sporadically across the other regions. Methylation of
the promoter of a CpG site leads to alterations in the
ability of that region of DNA to be expressed.15
These and other molecular processes involved in
phenotypic development were initially worked out
for the regulation of cellular differentiation and proliferation. All cells within the body contain the same
genetic sequence information, yet each cell lineage
has undergone specializations to become a skin cell,
hair cell, heart cell and so forth. These phenotypic
differences are inherited from mother cells to daughter cells. The process of differentiation involves the
expression of particular genes for each cell type in
response to cues from neighbouring cells and the
extracellular environment, and the suppression of
others. Genes that have been silenced at an earlier
stage remain silent after each cell division. Such
gene silencing provides each cell lineage with its characteristic pattern of gene expression. Since these epigenetic marks are faithfully duplicated across cell
division, stable cell differentiation results.16
The biochemical mechanisms of gene regulation perhaps first evolved to suppress viral infection of the
genome, but were then co-opted to allow cell differentiation and thus the evolution of multicellular organisms. Subsequently, they may have been further
co-opted for other functions across evolutionary time
including sexual differentiation involving chromatin
silencing in birds and mammals and parental genomic
imprinting in mammals.17
The epigenetic processes not only have taken on different functions over the course of evolution, but may
also be important in evolution. Indeed, profound
changes have occurred in the way that biological evolution is considered. Individuals play an active role in
their own development. Moreover, their activities can
impact on their descendants and how they evolve. For
instance, complex sequences of behaviour that were
initially learnt may, in the course of evolution, have
been expressed spontaneously without involving plastic mechanisms if the time and energy costs of doing
so were lower.1 The same principle can apply to environmentally induced responses affecting other
physiological systems. Adaptability affecting evolution
is commonly termed the Baldwin effect, although
Baldwin and those who published at the same time
as him were preceded a generation beforehand by
Douglas Spalding. A more appropriate and inclusive
term is the ‘adaptability driver’.18
Advances in molecular understanding are feeding
into an understanding that links studies of development to those of evolution. A central question in
considering evolutionary change driven by the environment is whether transmitted epigenetic changes
induced by developmental exposures in one generation could facilitate genomic change in later generations. In principle, they could if they increased the
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fitness of the individual carrying the markers and
subsequent genomic reorganization enabled some individuals to develop the same phenotype at lower
cost.1
Both male- and female-mediated epigenetic inheritance may be either direct or indirect. Direct epigenetic
inheritance refers to cases where the epigenetic mark
is transmitted through meiosis. In animals, and
particularly in plants, a growing body of evidence suggests that such transmission can occur and have
adaptive advantage.19 Indirect epigenetic inheritance
refers to the phenomenon of parental effects whereby
exposures in one generation can affect epigenetic
state in the next generation. In mammals, alterations
in maternal nutrition during pregnancy probably
induce epigenetic changes in the mother’s offspring.20
This effect may also extend to a second generation
because the germ cells that will form the gametes
that generate the F2 generation are formed when
the F1 generation is embryonic. In general, epigenetic
inheritance may serve to protect the better-adapted
phenotypes within the population until spontaneous
mutation leading to phenotypic fixation occurs.
Methylated cytosines are more likely to undergo
mutation to a thymine due to non-enzymatic
processes than are unmethylated cytosines or other
nucleotides.21 As a result, CG sequences are underrepresented in the genome. The consequent mutation
might mimic the phenotype induced by the methylation of that sequence thus fixing the phenotype,
or give rise to a range of phenotypes on which
Darwinian evolution could act. If epigenetic change
could affect and bias mutation rates, such
non-random mutation would facilitate fixation.1
A willingness to move between the different levels
of analysis has become essential for an understanding
of development and evolution. Simplifications are necessary as aids to discovery. Even so, the notion that
the organism’s characteristics are based on two
sources of instruction, one from within and one
from without, is far too simplistic. Other metaphors
such as the supposed hard-wiring of the brain or the
blueprint for development are equally unhelpful. The
conventional opposition of nature and nurture relates
to two different domains and should not be contrasted directly; indeed, one is a state and the other
a process. Nature properly refers to the fully developed characteristics of an organism and these will
depend on circumstances, and nurture should refer to
the ways in which those characteristics were derived
through development.
Even with this issue out of the way, the developmental processes embraced within the terms robustness and plasticity are commonly separated into
opposing categories. Knowing something of the
underlying regularities in development does bring an
understanding of what happens to the child as it
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INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
grows up. The ways in which learning is structured,
for instance, affect how the child makes use of environmental contingencies and how the child classifies
perceptual experience. Yet, predicting precisely how
an individual child will develop in the future from
knowledge of the developmental rules for learning is
no easier than predicting the moves in a chess game.
The rules influence the course of a life, but they do
not determine it. Like chess players, children are
active agents. They influence their environment and
are in turn affected by what they have done.
Furthermore, children’s responses to new conditions
will, like chess players’ responses, be refined or embellished as they gather experience.
Sometimes, the normal development of a particular
ability requires input from the environment at a particular time. What happens next, or even much later
in the life course, depends on the character of that
input. The upshot is that, despite their underlying
regularities, developmental processes seldom proceed
in straight lines. Big changes in the environment may
have no effect whatsoever because of processes ensuring robustness, whereas some small changes can have
big effects even if not immediately manifest. For example, it is now clear that subtle changes in the early
developmental environment have major influences on
how the mature human or experimental animal responds to an environment that leads to obesity.22 The
only way to unravel this path dependency is to understand the regulatory processes and their interplay
with the processes that generate change.
By bringing together evidence from different levels
of analysis, ranging from the molecular to the social,
a much more powerful theoretical perspective can be
formulated. Its impact is not only on scientific
approaches to development and evolution, but also
on how humans think about themselves and how
they design public health measures when mismatches
between themselves and their environment occur.23
Robustness and plasticity are complementary and
intertwined and must be considered together. They
should not be seen as being in opposition to each
other.
Leverhulme Trust and P. G. acknowledges the support
of the National Research Centre for Growth and
Development.
Conflict of interest: None declared.
References
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Acknowledgements
Sir Patrick Bateson FRS is Emeritus Professor of
Ethology at Cambridge University and Sir Peter
Gluckman FRS is University Distinguished Professor
and head of the Centre for Human Evolution,
Adaptation and Disease at the University of
Auckland. They jointly authored the recently published book ‘Plasticity, Robustness, Development and
Evolution’ (Cambridge University Press 2011). They
are very grateful to Felicia Low for her editorial
help. P. B. acknowledges the support of the
16
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WHY EVOLUTION NEEDS DEVELOPMENT, AND MEDICINE NEEDS EVOLUTION
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protein-restricted diet persistently alters the methylation
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Published by Oxford University Press on behalf of the International Epidemiological Association
ß The Author 2012; all rights reserved.
International Journal of Epidemiology 2012;41:223–229
doi:10.1093/ije/dys005
Why evolution needs development,
and medicine needs evolution
Christopher Kuzawa
Department of Anthropology, Northwestern University, 1810 Hinman Avenue, Evanston, IL 60208, USA.
E-mail: [email protected]
Accepted
10 January 2012
For much of the past century, adaptive evolution has
been defined as the differential replication of genes
that influence the survival or reproduction of their
host. Although Darwin is perhaps best remembered
today for having co-discovered this principle of
natural selection, its evolutionary importance was
not widely accepted until several decades after his
death. This is in part because Darwin lacked an
understanding of the material basis of heredity. His
speculations about the mechanism of inheritance, reflected in his Lamarckian model of pangenesis, had
fatal flaws. Notably, Darwin envisioned maternal
and paternal hereditary contributions to offspring as
blending together at conception; his critics noted that
this would inevitably lead to the dilution of any
novelties, and thus could not explain the gradual
rise of complex adaptations via the accumulation of
small changes as Darwin’s model required. This left a
major problem unsolved.
Working with his famous peas, Mendel showed that
crossing a pea plant possessing yellow seeds with another having green seeds did not produce offspring
with yellowish-green seeds; rather, the offspring
were either yellow or green. Nor was it the case
that two pea plants, one having smooth and one
having wrinkled peas, would yield offspring with
slightly wrinkled peas, as would be expected if the
characteristics of parents were blended at conception.
Instead, inheritance, at least for these traits, appeared
to be all or nothing, implying that the mode of inheritance was particulate in nature (Figure 1). Mendel’s
work thus showed a means by which novel traits
could be passed on to offspring with high fidelity,
and helped pave the way for widespread acceptance
of the Darwinian idea of natural selection.
Without knowledge of the molecular basis for genetic transmission, it was inevitable that the first examples of inheritance to be worked out would be
simple traits like pea colour. Although this simplicity
helped early geneticists infer that inheritance had particulate rather than blending qualities, and thus
advanced the field of evolutionary biology
Figure 1 Traits that follow a Mendelian pattern of inheritance, in this case smooth and wrinkled peas, are determined predictably by genotype; environmental input and
developmental plasticity are not important. Although such
traits are rare, they were among the first clear examples of
heredity to be worked out using the simple technologies
available to 19th- and early 20th-century researchers. This is
one among many reasons that developmental biology was
largely ignored within the foundations of modern genetics
and evolutionary biology