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Phil. Trans. R. Soc. B (2010) 365, 1717–1733
doi:10.1098/rstb.2010.0023
Introduction
Speciation genetics: current status and
evolving approaches
Jochen B. W. Wolf1,*, Johan Lindell1 and Niclas Backström1,2
1
Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University,
Norbyvägen 18D, 75236 Uppsala, Sweden
2
Department of Organismic and Evolutionary Biology, Harvard University, 26 Oxford Street,
Cambridge, MA 02138, USA
The view of species as entities subjected to natural selection and amenable to change put forth by
Charles Darwin and Alfred Wallace laid the conceptual foundation for understanding speciation.
Initially marred by a rudimental understanding of hereditary principles, evolutionists gained
appreciation of the mechanistic underpinnings of speciation following the merger of Mendelian genetic principles with Darwinian evolution. Only recently have we entered an era where deciphering
the molecular basis of speciation is within reach. Much focus has been devoted to the genetic
basis of intrinsic postzygotic isolation in model organisms and several hybrid incompatibility
genes have been successfully identified. However, concomitant with the recent technological
advancements in genome analysis and a newfound interest in the role of ecology in the differentiation process, speciation genetic research is becoming increasingly open to non-model
organisms. This development will expand speciation research beyond the traditional boundaries
and unveil the genetic basis of speciation from manifold perspectives and at various stages of the
splitting process. This review aims at providing an extensive overview of speciation genetics. Starting
from key historical developments and core concepts of speciation genetics, we focus much of our
attention on evolving approaches and introduce promising methodological approaches for future
research venues.
Keywords: selection; reproductive isolation; next generation sequencing; gene expression;
hybrid; speciation research in the post-genomic era
1. INTRODUCTION
The formation of new species lies at the very heart of
evolutionary biology. Indeed, the vast diversity of life
on Earth can only be explained by speciation, a process that continuously generates independently
evolving lineages. One and a half centuries ago, this
‘mystery of mysteries’ was subject to bold speculation,
as the philosopher John Herschel communicates in a
letter to Charles Lyell (Herschel 1836). Several years
later Charles Robert Darwin and Alfred Russell Wallace made a considerable contribution to demystify
the origin of new species and laid the foundation for
evolutionary biology by suggesting natural selection
and common ancestry as cornerstones of organismic
evolution (Darwin & Wallace 1858). Yet, despite its
title, Darwin’s opus ‘On the Origin of Species by
Means of Natural Selection’ (Darwin 1859) did not
focus on the rise of new species, but instead emphasized natural selection as a mechanism for the
adaptive change of populations in response to the prevailing conditions. Furthermore, Darwin highlighted
the transition from populations to species as a gradual
* Author for correspondence ([email protected]).
One contribution of 11 to a Theme Issue ‘Genomics of speciation’.
continuum (Mallet 2008) without formally treating
the isolation factors that reduce gene flow among
populations (Mayr 1942; see also Barraclough 2010;
Mallet 2010). However, Darwin lacked an understanding of the genetic basis of heredity. This eluded
evolutionary biology until four decades later, following
the rediscovery of Mendelian principles of inheritance
in 1900. Yet, it was not until the theoretical framework
of population genetics was amalgamated with Darwinian evolution and gave rise to the Modern Synthesis
during the 1930s that the species problem was
seriously considered (Dobzhansky 1937; Mayr
1942). This fusion put a premium on a population
genetic viewpoint and hence allowed examining the
speciation process from a genic perspective. By explicit
modelling, the Modern Synthesis and influential derivates such as the Neutral and Nearly Neutral Theory
(Kimura 1983; Ohta 1992) conceptually reduced the
evolutionary process to several tractable parameters
like mutation, drift, selection and recombination,
which can be estimated with empirical data. From
the excitement about modes and mechanisms of speciation that characterized the Modern Synthesis, a
consensus had emerged that speciation represented
complete reproductive isolation of biological species,
which could most likely be acquired through
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J. B. W. Wolf et al.
Introduction. Speciation genetics
geographic isolation (Mayr 1942). Speciation research
fell into a state of dormancy and largely revolved
around the relative importance of different geographic
speciation scenarios for several decades. However, one
and a half centuries after ‘On the Origin of Species’ there
is once again much excitement about speciation. Over
the last two decades, the spectrum of researchers with
an interest in speciation has expanded considerably.
Given the breadth of scientific disciplines that contribute to contemporary speciation research, this review is
naturally limited in focus and will capitalize on
research concerned with the genetics of speciation.
Genetic approaches have always been central to speciation research, but despite significant progress over
the last years in speciation genetic research, many fundamental questions about the molecular basis of the
splitting process await to be answered. Which genetic
elements are of particular relevance to speciation?
How many loci are involved, how large is the effect
of a specific locus and how important is epistasis or
pleiotropy? Where in the genome are the determinants
located and what is the importance of the genomic
landscape? What is the role of recombination,
mutation, chromosomal rearrangements, gene conversion and other molecular forces? How does divergence
in gene expression compare with structural changes?
How crucial is sex-linkage? Are different functional
classes of genes relevant at different stages of the speciation process? What is the role of natural selection
and how can we best detect its genetic footprints?
Finding full answers to even a subset of these questions over a broad taxonomic range will probably be
wishing for too much. Still, focusing on several wellchosen speciation models, we may come close to an
educated guess. Being empiricists, we will focus on
the empirical side by highlighting where recent
advancements have been and are expected to be
made and only mention the relevant theoretical work
in passing. We provide the conceptual background
on general key concepts where deemed necessary. As
much of recent research has focused on the role of
natural selection in speciation, the review reflects this
bias. We start by addressing research concerned with
the genetic basis of intrinsic postzygotic isolation,
which has been the traditional stronghold of speciation
genetics. We then expand the framework of speciation
genetics into an ecological context and try to infer how
the field will be transformed, as novel genomic tools
allow for detailed analysis of organisms, where previously no genomic resources have been available.
2. THE ROOTS OF SPECIATION GENETICS
Speciation involves the build-up of reproductive isolating barriers between diverging populations which are
most palpable in malfunctional heterospecific hybrids.
The evolution of postzygotic isolation giving rise to
hybrid problems posed an important challenge to
Darwinism: how can natural selection allow the production of maladaptive phenotypes and unfit
hybrids? Most speciation theories have subsequently
focused on resolving this dilemma. The theories can
be divided into two groups corresponding to distinct
forms of postzygotic isolation. In extrinsic postzygotic
Phil. Trans. R. Soc. B (2010)
isolation, hybrid phenotypes fare poorly in their interaction with the environment, falling between the
niches of the parental phenotypes (Schluter & Conte
2009). In intrinsic postzygotic isolation, hybrids are
unfit because they suffer inherent developmental
defects, resulting in partial or complete sterility or
inviability (Orr & Turelli 2001). There are numerous
examples from nature where both extrinsic and intrinsic postzygotic isolation appear to be at work (e.g.
Rogers & Bernatchez 2006; Rieseberg & Willis 2007;
Fuller 2008). Some recent work suggests that extrinsic
postzygotic isolation may be more common and more
important than intrinsic postzygotic isolation, specifically in the early stages of divergence (Schluter 2009;
Schluter & Conte 2009; Johannesson et al. 2010).
However, given the relative ease with which the genetic
basis of reproductive isolation can be evaluated in laboratory model organisms, along with a great amount of
theoretical work on the topic, most of what we know
about the genetics of speciation deals with intrinsic
postzygotic isolation.
Four kinds of genetic problems have been identified
as the likely causes of intrinsic hybrid difficulties:
ploidy levels, chromosomal rearrangements, genic
incompatibilities and interaction between nuclear genomes and endosymbionts, which can arguably be
regarded as a special case of the latter (Rieseberg
2001; Coyne & Orr 2004; Hoffmann & Rieseberg
2008). These mechanisms vary in importance depending on the system. Ploidy levels, for example, are of
major importance in plant speciation (Rieseberg &
Willis 2007), where chromosomal rearrangements
has also been extensively discussed (White 1969;
Hoffmann & Rieseberg 2008). In research on genetic
model organisms such as Drosophila (Kulathinal et al.
2009), there has also been much interest in chromosomal rearrangements (Noor et al. 2001; Noor & Feder
2006). Nevertheless, it appears that genic incompatibilities may be the most important cause of intrinsic
postzygotic isolation; they play a common role in
both hybrid sterility and inviability, and affect both
animals and plants (Orr & Turelli 2001; Coyne &
Orr 2004). Genic incompatibilities in hybrids most
commonly involve between-locus interactions; an
allele at one locus from one of the parental species
does not interact well with an allele at another locus
from the other parental species (Turelli & Orr 2000;
Coyne & Orr 2004). This in line with early suggestions
of the Modern Synthesis that negative epistatic
interactions among genes constitute a plausible mechanism that can cause hybrid sterility and inviability.
The ‘Dobzhansky –Muller’ model, initially discussed
by Bateson (1909) and later developed by Dobzhansky
(1937) and Muller (1942) (we will refer to it as
the Bateson – Dobzhansky – Muller (BDM) model
throughout), was proposed as a solution to the problem of how hybrid sterility can evolve without
selection opposing any intermediate step. In short,
allopatric populations that evolve independently each
accumulate different mutations that contribute to genetic differences between the populations. Subjected to
evolutionary forces including genetic drift and natural
selection, specific mutations may function well in
the genetic make-up of their particular population.
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Introduction. Speciation genetics
However, because alleles from different populations
have not been tested together, such mutations are on
average less likely to function with alleles of a different
ancestral background in hybrid individuals. Hybrid
sterility or inviability may therefore simply evolve as a
by-product of genomic differentiation after extended
periods of geographic separation. Accordingly, the
evolution of BDM incompatibilities provides an elegant solution to the production of unfit hybrids,
because natural selection need not oppose any step
in this process (Orr & Turelli 2001). BDM incompatibilities are expected to accumulate with the square of
the number of substitutions separating two species
(Orr & Turelli 2001). The emergence of reproductive
isolation through BDM is thus expected to be a slow
process that gets ever more efficient as time progresses
(Coyne & Orr 1997; Price & Bouvier 2002). If the
evolution of epistatic BDM incompatibilities were
commonplace, this ‘snowball effect’ of accelerating
decline in reproductive compatibility should generally
be visible. A recent exploratory meta-analysis by
Gourbière & Mallet (2010), however, suggests that
for most of the investigated taxa, the decay of reproductive compatibility is better predicted by linear or
slowdown models. This finding calls the general
importance of BDM compatibilities into question
and much rather suggests that incompatibilities
accumulate linearly without BDM effects and provides
novel evidence for a role of reinforcement. Further
meta-analyses of this kind are needed to better judge
the relative contribution of these processes in generating reproductive isolation.
Much of the research on intrinsic postzygotic isolation and genic incompatibilities has focused on
Haldane’s rule, the preferential effect of sterility or
inviability on hybrids of the heterogametic sex
(Haldane 1922). Following decades of relative stasis
in speciation genetics, the field was remarkably reinvigorated in the mid-1980s by newfound interest in this
phenomenon (Coyne 1985). Four main ideas have
been suggested as general causes of Haldane’s rule:
the dominance theory, the faster-male theory, the
faster-X theory and meiotic drive (Coyne & Orr
2004), with the two former recognized as main factors
in causing Haldane’s rule. New genomic data have
underscored the importance of sex chromosomes in
speciation (Mank et al. 2007; Presgraves 2008;
Ellegren 2008a). While Haldane’s rule is commonly
viewed as important in the initial stages of speciation
(Kulathinal & Singh 2008), it may, however, be
argued that sex chromosomes are comparatively
more important in later stages of speciation, completing the process following initial differentiation
(Qvarnström & Bailey 2008).
There has also been considerable debate regarding
how many and what type of genes are important in causing reproductive isolation. While the population genetic
approach of the Modern Synthesis held that adaptation
and population differentiation was the cumulative effect
of numerous genes, each with small effect (Fisher 1930),
recent research on intrinsic postzygotic isolation has
focused on the effect of a small number of genes each
with large effect (Orr 2001). This view is taken to the
extreme in research on bona fide speciation genes, of
Phil. Trans. R. Soc. B (2010)
J. B. W. Wolf et al.
1719
which only a handful of examples are known (Wittbrodt
et al. 1989; Ting et al. 1998; Barbash et al. 2000;
Presgraves et al. 2003; Ortı́z-Barrientos & Noor 2005;
Brideau et al. 2006; Mihola et al. 2009; Phadnis &
Orr 2009; Tang & Presgraves 2009). Only recently,
the first case was documented in which both genes of
a pair of epistatically interacting loci causing hybrid
incompatibility (Brideau et al. 2006; Presgraves 2007).
While further research is needed to resolve the function
of factors causing intrinsic postzygotic isolation, exciting
new evidence points to a role both for epigenetic interactions and genetic conflict (Orr et al. 2007; Mihola
et al. 2009; Phadnis & Orr 2009; Presgraves 2010).
A somewhat special case of gene– gene interactions
is given by mitonuclear interactions and may deserve
some extra attention. Until lately, the effect of endosymbionts on speciation has received comparatively
little attention and has largely focused on incompatibilities caused by cytoplasmically inherited parasites
like Wolbachia (Bordenstein et al. 2001). While mitochondrial DNA was long regarded as a neutral
marker invaluable for tracing evolutionary history
(Avise 2000), accumulating evidence questions the
assumption of neutrality, with implications for evolutionary biology including speciation (Meiklejohn
et al. 2007; Dowling et al. 2008). Specifically, as mitochondrial function is closely tied to energy production
through oxidative phosphorylation and organismal fitness (Rand et al. 2004), maladaptive combinations of
mitochondrial and nuclear genes in hybrids may act
to reduce gene flow and drive population differentiation (Dowling et al. 2008). For example, hybrid
breakdown owing to mitonuclear incompatibilities
(leading to reduced energy production) has been
observed in population crosses of marine copepods
(Ellison & Burton 2008) and Nasonia parasitoid
wasps (Ellison et al. 2008). Interestingly, large-scale
analysis of the Nasonia nuclear genome implies
strong effects of natural selection on nuclear genes of
relevance for mitochondrial function, in line with
strong selection for mitonuclear coadaptation
(TNGWG 2010). Incompatibilities between nuclear
and mitochondrial genes have also been shown to
cause hybrid sterility in yeast (Lee et al. 2008). Clearly,
the role of mitochondrial DNA in speciation deserves
further attention (Levin 2003; Gershoni et al. 2009)
and may explain intriguing patterns such as asymmetric introgression between incipient species
(Turelli & Moyle 2007).
The nature of hybrid sterility and infertility has not
only been elucidated by studies concerned with intrinsic postzygotic isolation. Investigations of postmating
prezygotic isolation in externally fertilized organisms
such as sea urchins and mussels have importantly contributed (Palumbi 2009). A plethora of approaches
over the last two decades have revealed that proteins
on gamete surfaces (e.g. bindin and lysin) are of
major importance in reducing gene flow by disrupting
fertilization (Lee et al. 1995; Metz & Palumbi 1996;
McCartney & Lessios 2004). Egg and sperm proteins
seem to have engaged in an arms race driven by sexual
conflict, which may accelerate the formation of reproductive isolation (Gavrilets 2000; Swanson & Vacquier
2002). Considered in isolation this would make for a
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Introduction. Speciation genetics
simple story. A combination of ecological, genetic and
physiological approaches, however, suggests that speciation in these systems include manifold processes
that may be simultaneously necessary for the emergence of discrete clusters. These include sexual
conflict, sperm competition, cryptic female choice,
frequency-dependent selection and reinforcement, as
well as ecological aspects such as individual density
distributions (Birkhead & Pizzari 2002; Swanson &
Vacquier 2002).
Both the examples of intrinsic postzygotic isolation
and postmating prezygotic isolation in external fertilizers highlight a role for genic interactions in the
build-up of reproductive isolation (referring in the
former case to epistatic interactions within one
hybrid individual, in the latter between proteins relevant for communication between gametes). They
also strengthen the idea that only few genes of major
importance may suffice in driving two populations
apart (Orr 2001).
3. EXTENDING THE FRAMEWORK OF
SPECIATION GENETICS
The considerable amount of data that has been collected on the basis of genetically encoded hybrid
incompatibilities over the last decades has biased our
view of speciation towards the genetics of postzygotic
isolation between rather divergent lineages. Conceptually however, the genetics of speciation has a much
broader definition, with speciation genes being functional genomic elements that convey some degree of
ecological, sexual, pre- or postmating, pre- or postzygotic isolation. Furthermore, as different genes will
act during different stages of the speciation process,
speciation research should encompass nascent species
as well as species that have accomplished a certain
degree of reproductive isolation (Via 2009). For
example, while understanding Haldane’s rule and the
action of BDM incompatibilities is undoubtedly
highly relevant, it remains unclear to what extent
observed incompatibilities have contributed to the
initial branching of lineages or if they merely reflect a
subsequent accumulation of incompatibility factors
completing the speciation process. Research into the
genetics of intrinsic postzygotic isolation therefore represents a retrospective look at the speciation process
(Via 2009), and an exclusive focus on hybrid sterility
and inviability will impede a deeper understanding
of the molecular basis of all aspects and stages of the
speciation process. Phylogenetic approaches including
taxa which already have diverged significantly can give
important insight into the tempo and mode of speciation (Price 2010). However, a strict retrospective
inference precludes a role of ecology a priori and can
thereby only speculate about the conditions under
which the speciation process was initiated. The evidence that prezygotic isolation seems to evolve faster
than postzygotic isolation (Coyne & Orr 1997) and
that postzygotic isolation can be achieved much more
readily if driven by extrinsic factors (Schluter &
Conte 2009) suggests that other approaches to
understanding the speciation process are needed.
Phil. Trans. R. Soc. B (2010)
Fortunately, current speciation research is also
embracing approaches that focus on the causes of
initial divergence in populations that are only partly
isolated (Via 2009). From such work on evolutionary
young lineages that are at incipient states of divergence, it has increasingly been recognized that
barriers to gene flow can evolve as a result of ecologically based divergent or disruptive selection. This
perception is bolstered both from theoretical work
evaluating the role of natural selection in a growing
number of empirical systems (Gavrilets 2004;
Dieckmann et al. 2004a; Gavrilets & Losos 2009;
Barton 2010). Clearly, a central limitation of this
forward-looking approach is that one cannot foresee
whether the speciation process will be driven to completion. Still, we predict that an approach combining
both ecology and genetics in young systems will be
fruitful, particularly so if the recently emerging genomic tools are applied to the well-established
ecological model systems with long study histories
(Kruuk & Hill 2008). Merging both worlds will eventually paint a broader picture of the relevant
mechanisms involved in speciation. In the following
sections, we highlight some areas where recent progress has been made towards understanding the role
of ecology and selection in speciation.
(a) Ecological speciation in a tube
One way to address the importance of ecologically
imposed divergent selection in speciation is given by
experimental evolution studies on micro-organisms.
This approach dates back to one of Darwin’s contemporaries, William Dallinger, but had not gathered
weight until the early 1990s. A number of in vitro
experiments have demonstrated that fitness trade-offs
between heterogeneous environments are easy to
achieve and can be stably maintained (Rainey &
Travisano 1998; Buckling et al. 2009). The genes
involved in adaptations can potentially be mapped
and in recent years it has become possible to monitor
the evolution of whole viral and prokaryotic genomes
and this will likely be increasingly feasible in eukaryotes (Bomblies & Weigel 2010). From these studies
it emerges that ecological adaptations often seem to
entail lowered hybrid fitness between divergent
lineages by negative epistatic interactions sensu BDM
incompatibilities (Dettman et al. 2007; Duffy et al.
2007; Barrick et al. 2009). This establishes the link
between ecological adaptation and postzygotic isolation and suggests that BDM incompatibilitities can
arise as incidental by-products of positive natural
selection (Dettman et al. 2007; Bomblies & Weigel
2010). The observation that most of the hybrid incompatibility genes identified so far show signatures of
adaptive evolution further supports this idea (Orr
et al. 2007; but see Presgraves 2010).
(b) Ecology and the concept
of adaptive speciation
Darwin was a clear proponent of the idea that environmental differences can generate divergent selection
pressures that eventually drive two populations apart.
He foreshadowed the idea that the splitting process
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Introduction. Speciation genetics
itself may be adaptive and not only a by-product of
geographical isolation (Darwin 1859). However, in
contrast to the experimental evolution studies
described above (which are essentially allopatric in
their setup), natural populations might be connected
by gene flow for some period of time and experience
gradually changing environments. The only realistic
scenario for the splitting process itself to be adaptive
then occurs by frequency-dependent intraspecific
interactions that can result in disruptive selection
(Dieckmann & Doebeli 1999). The most radical representation of such ecologically mediated speciation
is that of ‘adaptive speciation’, which refers to speciation processes in which the ‘splitting is an adaptive
response to disruptive selection caused by frequencydependent biological interactions’ (Dieckmann et al.
2004b). While this concept can, under special
circumstances, also work in allopatry it is essentially
related to speciation under conditions of gene flow
(‘divergence-with-gene-flow’).
While much of the literature on ‘ecological speciation’ revolves around similar ideas as in ‘adaptive
speciation’, ecological speciation is broader in its definition (Rundle & Nosil 2005) and encompasses all
instances whereby reproductive isolation can evolve
as a by-product of adaptation to different environments (Schluter 2001, 2009; Rundle & Nosil 2005).
Nonetheless, the two concepts have several features
in common that make them explicitly different from
neutral speciation models in allopatry caused by the
random accumulation of negative epistatic mutations.
A central theme of both is the importance of natural
selection acting on a set of few key traits associated
with resource use, mate choice or, in plants, pollination. Consequently, it is predicted that in the early
phase of the divergence process, taxa are reproductively isolated only at a small number of locally
confined areas in the genome (‘genomic islands of
speciation’), while remaining indistinguishable
throughout the parts of the genome that are unaffected
by selection (Turner et al. 2005; Harr 2006). During
the course of genomic differentiation, this divergence
mix slowly attains a higher degree of phylogenetic concordance through independent responses to genetic
drift and selection within the new species (Nosil
et al. 2009). Ecologically motivated speciation scenarios are thus genic in their view and put a premium
on the early stages of speciation, where speciation
boundaries are still porous and branching patterns
are established by a few, but crucial changes.
(c) Establishing empirical evidence for
divergence-with-gene-flow
Quantification of divergent or disruptive selection in
the wild is not trivial. Therefore, indirect means are
usually sought to evaluate the role of adaptation in speciation. For example, evidence for prezygotic isolation
between subpopulations from different environments
is indicative of adaptive differentiation. Examples
where habitat-based prezygotic isolation has been
documented include cichlid fish (Kocher 2004;
Barluenga et al. 2006; Elmer et al. 2010), Galapagos
finches (Grant & Grant 2008), guppies (Reznick
Phil. Trans. R. Soc. B (2010)
J. B. W. Wolf et al.
1721
et al. 2008), pea aphids (Hawthorne & Via 2001),
butterflies ( Jiggins et al. 2001), monkeyflowers
(Bradshaw & Schemske 2003) and other flowering
plant species (Lowry et al. 2008). Further evidence
for ecologically driven divergence comes from studies
examining the level of differentiation between subpopulations that have adapted to different environments as
opposed to subpopulations that reside in similar
environments (Funk et al. 2006). With an increasing
availability of analytical tools (Foll & Gaggiotti 2006),
we can expect that the environmental factors determining genetic structure in populations will be identified in
new systems.
An important observation that relies on a model of
speciation that invokes adaptation is the phenomenon
of parallel evolution, where similar ecotypes have
evolved repeatedly upon recurrent colonization of
new habitats (Schluter & Nagel 1995). Hard evidence
for parallel evolution is difficult to collect as it needs to
be demonstrated that parallel divergence is the result
of independent colonization events and not of subsequent gene flow between similar ecotypes (Schluter
2009). Still, there are examples from natural populations indicating that parallel speciation may occur.
A prominent case is given by the divergence of threespined stickleback ecotypes (limnetic versus benthic
and marine versus fresh water) (Rundle et al. 2000;
McKinnon et al. 2004). Similar adaptations to limnetic
and benthic niches are observed in lake whitefish
(Rogers & Bernatchez 2007; Whiteley et al. 2008;
Bernatchez et al. 2010) and arctic char (Skúlason
et al. 1996; Orr & Smith 1998). Other cases where parallel speciation seems to be in progress include
adaptations to environments with and without predators in mosquitofish (Langerhans et al. 2007),
adaptations to areas of different wave exposure in
snails (Sadedin et al. 2009; Johannesson et al. 2010;
Butlin in press), and adaptations to different host
plants in walking sticks (Nosil et al. 2008) and pea
aphids (Peccoud et al. 2009).
(d) Adaptations from novel mutations or
standing genetic variation?
Common to the examples listed above is that parallel
divergence occurred within thousands rather than
millions of years. Given the speed of the process, it is
most probable that genetic variants underlying a
given adaptive phenotype are independently recruited
from standing genetic variation, since adaptation
restricted to selection of novel mutations would be
far slower (Barrett & Schluter 2008). There are
indeed some well-established cases of adaptive divergence occurring as a result of recent selection for
particular alleles recruited from ancestral polymorphism (Schluter & Conte 2009). For example,
phylogenetic studies in sticklebacks have shown that
stream living, less-armoured ecotypes have arisen
independently several times at different locations, but
that the alleles contributing to body armouring
(Ectodysplasin, Eda) were already present in their
common ancestor (Colosimo et al. 2005). In the comparable case of lake whitefish (Rogers & Bernatchez
2007; Whiteley et al. 2008; Jeukens et al. 2009;
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Introduction. Speciation genetics
Bernatchez et al. 2010), it is likely that standing genetic
variation has contributed since the ecotypes evolved
repeatedly, in parallel, in very recent times. A fascinating case has been reported for the apple maggot,
Rhagoletis pomonella. In this species, a particular ecotype started using domestic apple instead of
hawthorn and in less than two centuries this change
in behaviour has caused almost complete reproductive
isolation between these ecotypes (Feder et al.
2003a,b).
While many of the examples of parallel speciation
might be indicative of selection on standing genetic
variation, caution needs to be taken. In sticklebacks,
the Pituitary homeobox transcription factor 1 (Pitx1)
locus has been shown to be involved in the development of the pelvic apparatus. Comparable to the
situation of armour plating described above, most
sticklebacks develop a normal pelvic apparatus. In
over a dozen widely distributed populations, however,
phenotypes with reduced spines seem to have evolved
in parallel and seem to be under selection as a response
to habitat-related factors such as predator pressure or
calcium availability (see Shapiro et al. 2006 and references therein). Chan et al. (2010) have recently
demonstrated that recurrent deletions in a highly
mutable enhancer region of the Pitx1 gene, rather
than recruitment from ancestral variation, are
responsible for a phenotype with reduced pelvic
spines.
(e) The problem of recombination
In the early stages of adaptive divergence, reproductive
isolation is expected to be concentrated around a small
number of locally adapted genes. It remains an important challenge to understand how reproductive
isolation progresses from a genetic mosaic pattern to
genome-wide divergence. Particularly, under conditions with homogenizing gene flow, the association
between genes involved in local adaptation and those
influencing premating isolation are generally considered to be vital (Rundle & Nosil 2005; Bolnick &
Fitzpatrick 2007). A key problem in speciation-withgene-flow models is therefore to understand how
natural selection can maintain adaptive gene combinations when faced with the deteriorating force of
recombination. Several possibilities to overcome the
disruptive influence of recombination have been
suggested, including close physical linkage (Butlin
2005), reduction in effective recombination rate in
the regions under diversifying selection (Via & West
2008) and pleiotropy (Kirkpatrick & Barton 1997;
Kirkpatrick & Ravigné 2002). These scenarios are
hard to disentangle as long as the causative variants
for both isolation and adaptation have not been elucidated (Rundle & Nosil 2005). Still, to understand the
strength of selection needed to result in the build-up
of reproductive isolation, an effort to discriminate
them is essential. At present, the genetic elements governing the traits involved in ecological speciation remain
largely unknown. Chromosomal speciation models
postulate an important role for rearrangements in the
build-up of reproductive isolation among incipient
species (Rieseberg 2001; Hoffmann & Rieseberg
Phil. Trans. R. Soc. B (2010)
2008). Indeed, rearrangements have been found to be
associated with hybrid inviability for example in
Helianthus sunflowers (Rieseberg et al. 1999) and
Drosophila (Noor et al. 2001; Brown et al. 2004).
Chromosome rearrangements definitely provide a
means to resolve the problem of linkage, but of
course require that major causative variants for both
isolation and adaptation are located within the inverted
region.
Pleiotropic genes are particularly attractive candidates, as they entirely bypass the problems of linkage
and recombination. By definition, pleiotropy occurs
when a single gene influences several phenotypic
traits. Translated into the speciation context, they
convey habitat-specific selective advantage and at the
same time ensure assortative mating with reference
to the trait under selection. Examples from several
studies point towards their existence. Beak size in
Darwin’s finches is both relevant to ecologically mediated
fitness and species recognition (Grant & Grant 2008);
the genetic background to beak shape seems to be largely
confined to one locus involved in the calmodulin pathway
(Abzhanov et al. 2006). Empirical data also indicate
that pleiotropy might govern copper tolerance and pollinator shifts in monkeyflowers (Macnair & Christie
1983; Bradshaw & Schemske 2003), and the coupling
of reproductive isolation and host switch in pea aphids
(Hawthorne & Via 2001). In addition, wing colour and
mate preference actually map to the same gene (wingless)
in butterflies (Kronforst et al. 2006) and many floral traits
that affect pollinator shift in columbines seem to be
restricted to a small genomic region (Hodges et al.
2002). However, causative variants are not fine-mapped
and verified and the results could also be explained if
there is tight linkage between the locus governing local
adaptation and the locus governing reproductive isolation
(Rundle & Nosil 2005). Another way of establishing
evidence for pleiotropic genes could potentially come
from candidate gene approaches. While rapidly developing genomic tools will soon allow examining classes of
candidate genes (e.g. pigmentation genes, early development genes) or entire gene families (Mamanova et al.
2010), candidate gene approaches are at present still limited to a handful of genes. For example, the major
histocompatibility locus (MHC) has been extensively
studied in a behavioural ecological framework. Pleiotropy
with regard to parasite resistance and signal for mate
choice make it a good candidate for studies on ecological
speciation under conditions of gene flow (Eizaguirre et al.
2009). Another extensively studied class of genes that
may be relevant to speciation are pigmentation
genes like the melanocortin-1-receptor (MC1R) or the
Agouti signalling protein (ASIP1) that have been
shown to influence coat and plumage colour in several
organisms (Mundy et al. 2004; Hoekstra et al. 2006;
Linnen et al. 2009). It is intuitively clear that the
match between body coloration and substrate is relevant to predator-mediated selection, as has been
recently shown for Peromyscus mice (Mullen et al.
2009). Another convincing non-genic mechanism
that generates an immediate association between
ecological adaptation and mate choice is habitat
learning (Beltman & Haccou 2005), which has been
suggested to be relevant in several vertebrate systems
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Introduction. Speciation genetics
(Musiani et al. 2007; Wolf et al. 2008). One has to be
careful, however, to a priori attribute the link between
ecological adaptation and assortative mating to
learning, as simple non-genic mechanism of assortative
mating, in which the mating trait arises as a pleiotropic
effect of genes responsible for ecological adaptation,
is also credible in viral evolution (Duffy et al. 2007).
Pleiotropy certainly is an appealing idea, but to date
it remains unclear to what extent the different mechanisms of coupling the trait under selection and
assortative mating are involved. Regardless, the studies
mentioned above show that the coupling seems to be
possible and rather widespread.
(f) A role for sexual selection
While sexual selection in itself need not be linked to
ecological speciation (Schluter 2001, 2009), it has
been discussed as a means to enhance divergence in
an ecological context (Grant & Grant 1997; Edwards
et al. 2005; Ritchie 2007; van Doorn et al. 2009).
Under certain circumstances, the effect of a sexually
selected trait depends on the environment in which it
is displayed, so that the divergence in mating traits
will eventually be governed by adaptation to the
environment (‘sensory drive’; Boughman 2002). In a
recent study, Seehausen et al. (2008) established the
link between colour variants in cichlid fishes and
water turbidity and provided compelling evidence for
speciation through sensory drive in sympatry.
Although sensory drive may promote speciation in
some systems, it is conceivable that other modes of
sexual selection are the driving forces of speciation
(e.g. good genes (Andersson 1994) or Fisherian runaway selection (Fisher 1930; Kirkpatrick & Hall
2004)). Specific examples where sexual selection has
been argued to promote divergence include the rapid
diversification of cichlid fish (Seehausen et al. 1999;
Kocher 2004; Elmer et al. 2010) and cricket species
(Shaw & Parsons 2002; Mendelson & Shaw 2005).
Theory predicts that sexual selection is expected to
be more powerful in organisms with female heterogamety (Reeve & Pfennig 2003), such as birds and
lepidopterans. There is indeed some empirical indication that traits of importance for species
recognition are sexually selected in Heliconius butterflies (suggesting a role for the wingless locus;
Kronforst et al. 2006) and Ficedula flycatchers
(Sæther et al. 2007; Qvarnström et al. 2010). Interestingly, in the case of flycatchers there is character
displacement, presumably driven by reinforcement
(Sætre et al. 1997), and in crickets, butterflies and flycatchers there is also evidence for physical linkage of
trait and preference loci, which could partly resolve
the problem of recombination. One important point
is that in most cases where sexual selection has been
the suggested force of speciation, it is still to be
resolved if the differentiation has evolved as a
by-product of diversifying selection driven by environmental factors (ecological speciation) or through
fixation by sexual selection of different mutations in
populations with similar selection regimes (Ritchie
2007).
Phil. Trans. R. Soc. B (2010)
J. B. W. Wolf et al.
1723
A fresh perspective on how sexual selection could
facilitate speciation under sympatric conditions has
been put forth by van Doorn et al. (2009). In a
simple model, the authors explore how sexual selection and disruptive ecological selection can join
forces to curtail gene flow, promote local adaptation
and eventually lead to speciation. Key to their
model is the incorporation of condition-dependent
mate choice, which only involves a pre-existing
mate choice machinery instead of having to rely
on concomitant divergence of ecologically and arbitrary sexually selected traits. By the introduction of
this genotype-by-environment interaction they
entirely circumvent the problem of earlier models
to link ecological performance and assortative
mating without having to invoke the presence of
fortuitous pleiotropy between ecological and
mating traits.
4. GETTING TO THE GENES UNDER SELECTION
Much progress has been made over the last years in
identifying the genes responsible for BDM incompatibilities in model organisms (see above), but the
quest for genes underlying adaptive divergence in
organisms of ecological interest where few genetic
resources are available has only begun. Bringing wild
strains into the laboratory will not yield the same
clear-cut insights as in the study of postzygotic
hybrid breakdown even if the same genetic tools
existed as for model species like Drosophila. The fitness
effect of a given trait (and its underlying genetic basis)
should preferably be investigated under the full set of
environmental conditions in the wild and will be difficult to study under laboratory conditions (Calisi &
Bentley 2009). The quest is further exacerbated by
the fact that traits important for local adaptation are
likely to be quantitative and are hence thought to
have a complex genetic background (Weedon &
Frayling 2008; Hendry 2009). In the years to come,
many efforts will nonetheless be devoted to deciphering the genetic basis of speciation driven by adaptive
divergence. Although getting to specific genes will
understandably be difficult in most cases, much progress is expected in finding candidate regions of
interest and in answering more general questions
about the underlying genetic mechanisms. Is extensive
adaptive divergence based on few loci with major effect
(Gavrilets & Losos 2009) or by many loci of small
effect (Fisher 1930)? Do gene interactions between
traits undergoing adaptive divergence also lead to
intrinsic postzygotic isolation? Are candidate genes
special with regard to the level of pleiotropy or their
position in protein networks? How is the homogenizing effect of gene flow and recombination overcome?
In the following, we will shortly mention some
promising avenues for addressing these questions.
(a) Phenotype – genotype association
Most investigations conducted in natural populations
so far have used a limited number of genetic markers,
typically tens to thousands of microsatellites or amplified fragment-length polymorphisms (AFLPs), which
are suboptimal with regard to large-scale genome
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J. B. W. Wolf et al.
Introduction. Speciation genetics
scans (Butlin in press). The advent of massively parallel sequencing technologies holds much promise for
speeding up the progress in understanding the genetic
basis of (ecological) speciation (Noor & Feder 2006;
Ellegren 2008b; Vera et al. 2008; Gilad et al. 2009).
The scope of these recent fast developing methods is
nicely illustrated by a collation of 21 articles on next
generation molecular ecology (Tautz et al. 2010).
Once statistical challenges of how to appropriately
deal with short-read shotgun sequences in a population genetic context are overcome, population
genomic analysis will be directly based on the sequencing data itself and replace the marker-based
approaches. At present still, the most straightforward
application consists in scanning large proportions of
the genome for polymorphisms that may be used as
genetic markers for subsequent genotyping using
array-based high-throughput genotyping techniques
(Syvänen 2005). The increase of genetic markers by
orders of magnitudes is expected to boost genetic
mapping studies that have been so far often limited
by the number of available markers. The first step in
establishing the link between phenotype and genotype
usually involves obtaining a detailed linkage map. In a
few natural populations, this has already been achieved
(e.g. Wang & Porter 2004; Stemshorn et al. 2005;
Gharbi et al. 2006; Åkesson et al. 2007; Rogers et al.
2007; Backström et al. 2008). Nonetheless, such pedigree-based approaches require access to multigeneration samples of related individuals; that can be
extremely challenging in natural populations, and
again stresses the importance of long-term ecological
model systems for the study of speciation.
With the availability of larger marker sets one could
anticipate that mapping efforts will be focused on
other methods, such as association scans (linkage disequilibrium mapping) using population samples, an
approach most well developed in model species with
the available genome sequences (Nordborg & Weigel
2008; Goddard & Hayes 2009; Bomblies & Weigel
2010). In divergent natural populations or hybrid
zones, it may be of particular interest to make use of
the extended linkage disequilibrium resulting from
the admixture of differentiated populations (Rieseberg
& Buerkle 2002; Smith & O’Brien 2005). Recent progress in analytical approaches (Gompert & Buerkle
2009) further increases the applicability of this
method making a strict geographical sampling regime
dispensable. A striking example demonstrating the
potential of this approach comes from a study on the
genetics of introgression across Cottus hybrid zones,
which basically suggests that different forms of selection affect much of the genome and provides
numerous candidate regions for future studies (Nolte
et al. 2009). While extended linkage after admixture
is useful for identifying the genomic regions of interest,
short-range linkage disequilibrium is needed to be able
to resolve selection at the level of the gene. However,
adaptive divergence may put a lower boundary on
the resolution with which genes can be mapped, as
selection can reduce the effective (interspecific/interpopulation)
recombination
rates
in
regions
harbouring genetic determinants of local adaptation
(‘divergence hitchhiking’; Via & West 2008). This
Phil. Trans. R. Soc. B (2010)
results in large regions spanning significant portions
of the genome increasing the degree of differentiation
at marker loci located far from the target of selection
(but see Yatabe et al. 2007; Wood et al. 2008). Nevertheless, as exemplified in disease-mapping studies in
dog, there may still be potential for designing mapping
studies so that within-breed long-range linkage disequilibrium (admixture or divergence hitchhiking in
the case of incipient species) is used to find candidate
regions and then between-breed short-range linkage
disequilibrium (within species) allows for more
detailed searches (Sutter et al. 2004; Lindblad-Toh
et al. 2005).
Additional possibilities to characterize the genes
involved in early speciation spring from the ever
increasing characterization of gene function in model
species from where it will be possible to extract candidate loci for investigation in the focal species (Hoekstra
et al. 2004; Mundy 2005). This approach certainly
takes the risk that there might be different genetic
backgrounds to similar phenotypes also between closely related species or between populations within
species (Hoekstra & Nachman 2003).
(b) Phenotype uninformed methods:
evolutionary genomics
All the above-mentioned approaches require some previous knowledge about the phenotype involved in the
adaptive process (top down; mapping). An alternative
approach lies in the application of population genetic
approaches to detect selection directly from DNA
sequence data without a priori knowledge of the phenotypic effect (bottom-up; evolutionary genomics).
With an ever increasing availability of genome-wide
polymorphism and divergence data, it will be possible
to scan genomes of diverging populations for regions
with higher than expected differentiation indicative
of ongoing or recent diversifying selection (Akey
et al. 2004; Beaumont 2005; Excoffier et al. 2009).
Additionally, high-density marker data can be used
to trace regions indicative of recent directional selection (selective sweeps) within populations (Nielsen
2005; Nachman 2006). An example of where this
approach has been successfully applied comes from
wild mice populations (Harr 2006; Teschke et al.
2008). However, it is well recognized that population
structure and other demographic scenarios can
severely affect the expected distribution of parameter
values (Thornton & Andolfatto 2006; Pool & Nielsen
2007; Excoffier et al. 2009; Hermisson 2009).
Encouragingly, numerous methods have been developed to estimate the demographic scenario under
which to search for the footprints of selection (Hey &
Nielsen 2004; Hey 2006; Becquet & Przeworski
2007). Clearly, studies on rich datasets that infer selection under detailed demographic scenarios will set the
future standards (Nielsen et al. 2009).
Valuable insights into the genetic basis of adaptation may further come from comparative genomic
studies that set out to find signatures of selection by
comparing sequences of orthologous genes from two
or more organisms (Ellegren 2008a). Genes affected
by diversifying selection on protein structure are
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Introduction. Speciation genetics
expected to have a higher ratio of non-synonymous to
synonymous differences among taxa than genes that
evolve under purifying selection. For this approach
to be meaningful, however, the number of fixed
mutations must clearly exceed the number
of polymorphisms, which restricts it to comparisons
of lineages that have speciated millions of years ago.
Still, it may be informative if we consider which
genes or gene ontology classes are repeatedly identified
to be under positive selection, as these genes may also
be involved in earlier stages of the splitting process. A
complementary approach that can identify the spread
of beneficial mutations in single lineages consists of
contrasting polymorphism to divergence data between
species with McDonald – Kreitman (McDonald &
Kreitman 1991) and Hudson – Kreitman – Aguadetype (Hudson et al. 1987) approaches (Begun et al.
2007).
So far, past comparative genomic approaches have
been limited to a small number of organisms where
whole genome sequences have been available (Kosiol
et al. 2008). Having entered the era of massively parallel sequencing, this will rapidly change and the first
large-scale examples of comparative genomic analyses
on non-model organisms are being published (Künstner et al. 2010).
5. A ROLE FOR GENE EXPRESSION IN
SPECIATION
(a) Structural variation versus variation in
expression
Thirty-five years ago, King & Wilson (1975) expressed
their amazement that homologous protein and DNA
sequences appeared to be almost identical between
humans and chimpanzees. This influential paper
touched upon an important concept whose basic postulate is still valid. Functional polymorphism in genes
relevant to evolutionary change is not restricted to
coding variation, which ultimately alters amino acid
composition and protein structure; it also includes
regulatory variation modulating the expression of a
gene. Several lines of research have made clear that
changes in gene expression are indeed relevant in speciation (Tautz 2000; Wittkopp et al. 2008). This
applies to a broad variety of taxa and ranges from
colour patches in the wings of flies (Gompel et al.
2005) to beak size in Galapagos finches (Abzhanov
et al. 2006). While the evolutionary implications of
structural variation have been extensively explored in
an evolutionary framework both in theory and practice, scrutiny of the evolution of gene expression
remains a big challenge.
Analysis of the role of gene expression in speciation
faces many obstacles. Part of this relates to technological restrictions. For studying structural variation, the
one-dimensional DNA sequence can nowadays be
read with great ease and the amino acid composition
can directly be derived from the genetic code. However, it is technically more demanding to work with
RNA and quantify gene expression. In contrast to
DNA sequencing, where clear quality standards have
been established that enable comparative results
across laboratories, quantification of transcript
Phil. Trans. R. Soc. B (2010)
J. B. W. Wolf et al.
1725
abundance differs between technologies such as qRTPCR and microarray studies. Furthermore, gene
expression studies often fail to reflect the (major)
quantity of interest: protein abundance (Schrimpf
et al. 2009). Nonetheless, the development of promising new approaches (Wang et al. 2009) will facilitate
investigations of the role of gene expression in speciation. Instead, biological complexity may pose a greater
challenge. Numerous complex and interacting processes like transcription, transcript stability, splicing,
regulatory RNAs and translational efficiency eventually determine protein abundance in a cell and it is
difficult to make allowances for all. Another complicating factor is the sometimes widely different expression
profiles among tissues and developmental stages,
which makes it hard to pick the right time and place
to study the evolution of expression differences
between lineages. Similarly, expression profiles are
notoriously plastic (Cheviron et al. 2008), which
limits expression studies to species that can be bred
under common garden conditions with relative ease.
Despite the analytical difficulties associated with
studying gene expression, a body of literature has accumulated over the last years showing that regulatory
variants are a primary substrate for the evolution of
species (Wray 2007). In the past, it has been customary
to focus on structural sequence variation and consider
each gene as a separate unit of evolution in both population genetic theory and empirical practice. However,
phenotypic traits are controlled by a large number of
different genes and changes in their temporal and spatial
coordination have far-reaching consequences. Stern &
Orgogozo (2009) posit that once we start considering
the interactions of genes and transcripts, we may understand that not all genes are equal in the eyes of evolution,
and that evolutionarily relevant changes may accumulate
in certain hotspot genes located at specific positions in
regulatory networks. Results of experimental evolution
studies corroborate this claim (Cooper et al. 2003).
Tapping the full potential of such a perspective can
shed new light on evolutionary phenomena like parallel
evolution in divergent lineages that are difficult to explain
otherwise. For example, does parallel speciation commonly involve parallel changes in expression patterns,
following strong selection for particular beneficial alleles
(Unckless & Orr 2009)? The integration of network
thinking into evolutionary genetics may constitute a
similar quantum leap as the integration of Mendelian
genetics into Darwin’s evolutionary framework
(Koonin 2009). Without doubt, the burgeoning interest
in the contribution of gene expression to species
divergence is part of this transition.
(b) A role for selection on gene expression?
Under the assumption that most characters are controlled by a large number of interacting genes, we can
expect that the underlying genetic network may be largely resilient to slightly deleterious changes in one of its
elements. Likewise, advantageous mutations may not
be manifested significantly in a genetic pathway with
many developmental ramifications (Wagner 2000).
Many features of transcriptional networks may indeed
be described by non-adaptive processes and a non-
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J. B. W. Wolf et al.
Introduction. Speciation genetics
negligible number of regulatory changes may thus be
expected to evolve approximately in a neutral fashion
(Lynch 2007). Khaitovich et al. (2005) have laid out
the theoretical basis for a neutral evolutionary model of
gene expression which predicts an approximately linear
accumulation of expression differences with time as
well as a correlation of expression variance within a
species and expression differences between species. Several studies explicitly addressing this question are in line
with a predominantly neutral scenario (Khaitovich et al.
2004; Staubach et al. 2010). If divergence in gene
expression progresses simply as a function of time in a
largely neutral fashion, we may expect regulatory incompatibilities to arise analogous to the BDM model for
structural variation. Indeed, experimental evidence
suggests that divergence in gene regulation is a major
contributor to BDM incompatibilities between several
species of Drosophila (Haerty & Singh 2006), which
may be a more widespread phenomenon as hybrid misexpression between taxa is not restricted to drosophilids
(Cowles et al. 2002; Tirosh et al. 2009). Still, it may be
premature to argue that regulatory incompatibilities generally arise analogous to genetic incompatibilities sensu
the BDM model. Alternative scenarios such as compensatory changes among interacting gene products or gene
products and regulatory elements need to be taken into
consideration (Landry et al. 2007).
(c) Cis or trans?
The study of hybrid mis-expression has also proven to
yield valuable insights on the relative role of trans and
cis factors in the evolution of novel phenotypes.
Changes in cis-acting sites occur on the regulatory
sequences of the gene itself. This way, their effect is
restricted to the sequences of their own DNA (or
RNA) molecule. Trans factors (such as transcription
factors) on the other hand are separate molecules (proteins or RNAs) that can influence the activity of a
broad variety of targets. Studies in several model
species suggest that expression divergence is predominantly owing to changes in cis factors (Wray 2007;
Wittkopp et al. 2008). A broad study in yeast (Tirosh
et al. 2009) further suggests that upstream components involved in transduction of environmental or
internal signals to direct regulatory elements (sensory
trans factors) seem to be more often involved than
direct transcription and chromatin regulators (regulatory trans factors). Taken together, these results suggest
that not all divergence processes are strictly neutral.
Reviewing the empirical evidence to date, Fay &
Wittkopp (2008) conclude that adaptation often
occurs by changes in gene regulation and that cisregulatory sequences appear to play a special role
in adaptive divergence.
What is the evolutionary relevance of cis-regulatory
changes and how can they affect the speciation process?
It is often proposed that natural selection can operate
more efficiently on cis-regulatory mutations. First,
alleles in diploid organisms are largely transcribed independently suggesting that—in contrast to structural
mutations that are mostly recessive—mutations in cisregulatory sequences are often co-dominant and
thereby directly accessible to selection (see Wray 2007
Phil. Trans. R. Soc. B (2010)
and references therein). Second, modular organization
and tissue-specific expression governed by enhancer
elements reduce the degree of negative pleiotropy.
Wray (2007) and Prud’homme et al. (2007) provide a
broad array of empirical examples that nicely illustrate
the vast creative potential of cis-regulatory evolution.
In sticklebacks, for instance, cis-regulatory changes in
the Pitx1 gene seem to be associated with differences
in pelvic skeleton structure between marine and freshwater forms (Shapiro et al. 2004; Chan et al. 2010).
The repeated evolution of pelvic reduction in freshwater
populations is not limited to populations of the threespined sticklebacks, but can also be observed in the distantly related lineage of nine-spined sticklebacks
(Pingitius pungitius; Shapiro et al. 2006). This observation of repeated habitat-associated changes in the
regulatory region of Ptx1 is not only suggestive of a
role in cis-elements in parallel evolution, but it also
underlines the importance of studying the genetic
basis of speciation in combination with ecological
research. It will be of crucial importance to our understanding of regulatory divergence processes to apply
genomic tools to non-model species that have been
extensively studied on morphological, ecological and
behavioural grounds.
(d) Expression studies in non-model organisms
A few years ago genomic studies of gene expression
in non-model organisms were out of reach. Today, they
certainly still constitute a technological challenge, as
genomic resources are, with the exception of a few speciation models like Anopheles (Cassone et al. 2008),
usually unavailable. Interspecific microarrays have been
successfully applied (Cheviron et al. 2008; Renaut et al.
2009), but will always remain a compromise. We can
expect, however, that digital measures of expression on
the basis of next generation sequencing (RNAseq) will
be a major breakthrough (Gilad et al. 2009; Wang et al.
2009). As sequence and expression data are simultaneously generated, this approach has the advantage
that structural and expression divergence can be directly
compared. It further enables a much more detailed view
on expression, e.g. by considering allele-specific
expression patterns (Fontanillas et al. 2010) or by characterizing splicing variants (Harr & Turner 2010), which
are not tractable by interspecific microarrays. First
studies exploring the potential of RNAseq in nonmodel organisms which rely on distant genomic
resources are promising (Buggs et al. 2010; Goetz et al.
2010; Wolf et al. 2010) and document the dawning of
an era where high-resolution transcript-profiling in
non-model organisms will become commonplace
(Gilad et al. 2009).
6. CONCLUSION
Since the conception of evolutionary biology, interest
in speciation has gone through periods of intense discussion and times of relative stasis. Over the last two
decades speciation research has gained enough
momentum to address the genetics of the splitting process in earnest. This advancement has primarily been
driven by an interest in the genetics of intrinsic postzygotic isolation with particular reference to genic
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Introduction. Speciation genetics
incompatibilities. Despite considerable achievements,
this field undoubtedly awaits further insights. Experimental studies will continue to contribute to the
understanding of divergent selection in the accumulation of genic incompatibilities and the fast
development in massive parallel sequencing technologies now makes it affordable to monitor the
evolutionary process across entire genomes.
Technological and analytical developments and a
newfound interest in the role of ecology in promoting
differentiation have recently encouraged speciation
genetic research to broaden its perspective. From
being confined to the study of genic incompatibilities
in hybrid crosses, speciation genetics now extends to
research on the forces involved in the initial phase of
the speciation process and the role played by diversifying selection. This development enhances the chance
to establish the link between phenotypes and genotypes and to bring the study of speciation into the
wild. Population genomic analyses and studies on the
role of expression and copy number variation will
soon be common practice also in non-model organisms. A burgeoning field of great potential herein is
the genomics of hybrid zones where generations of
hybrid and backcross individuals lay the foundation
for genome scans, taking advantage of differences in
within- and between-population levels of linkage disequilibrium. Similarly, long studied ecological
models with well-established pedigree information
and knowledge on traits involved in reproductive isolation will remain highly valuable resources. In
particular, wild species that can be kept under controlled conditions bear the potential to reveal the
underlying genetic causes of speciation. Finally and
unquestionably, unravelling the mechanistic foundations underlying the ‘mystery of mysteries’ will
ever more benefit from combining the expertise from
many fields.
This review results from a symposium on speciation entitled
‘Origin of Species –150 Years Later’, held at the Sven Lovén
Center for Marine Sciences in Fiskebäckskil, Sweden.
We would like to thank the organizers Hans Ellegren,
Staffan Ulfstrand and Michael Thorndyke along with the
Wenner-Gren Foundation and the Royal Swedish Academy
of Sciences who made this meeting possible. We are also
grateful to Richard Bailey and one anonymous referee for
helpful comments and also thank Elizabeth Gold for
helping to improve the English throughout the manuscript.
We further acknowledge post-doctoral research funding
from the Volkswagen Foundation (grant: I/83496 to
J.B.W.W.), the Swedish Research Council FORMAS
(grant: 2008-1840 to J.L.) and the Swedish Research
Council (grant: 2009-693 to N.B.), respectively.
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