genetics of climate change adaptation

8/11/2019 Genetics of Climate Change Adaptation

1/28

Genetics of ClimateChange AdaptationSteven J. Franks1 and Ary A. Hoffmann2, 1Department of Biological Sciences, Fordham University, Bronx, New York 10458;email: [email protected] of Genetics, University of Melbourne, Parkville, Victoria 3010 Australiaemail: [email protected]

Annu. Rev. Genet. 2012. 46:185208

First published online as a Review in Advance on August 29, 2012

The Annual Review of Genetics is online at genet.annualreviews.org

This articles doi:10.1146/annurev-genet-110711-155511

Copyright c 2012 by Annual Reviews. All rights reserved

0066-4197/12/1201-0185$20.00 Corresponding author

Keywordsevolutionary constraints, epigenetics, genetic response networks,global change, natural selection

Abstract The rapid rate of current global climate change is having strong efon many species and, at least in some cases, is driving evolution, pularly when changes in conditions alter patterns of selection. Climchange thus provides an opportunity for the study of the genetic bof adaptation. Such studies include a variety of observational and eximental approaches, such as sampling across clines, articial evolexperiments, and resurrection studies. These approaches can be cobined with a number of techniques in genetics and genomics, incing association and mapping analyses, genome scans, and transcripproling.Recent research has revealed a numberof candidate genestentially involved in climate change adaptation and has also illustthat genetic regulatory networks and epigenetic effects may be partlarly relevant for evolution driven by climate change. Although genand genomic data are rapidly accumulating, we still have much to about the genetic architecture of climate change adaptation.

185

Click here for quick links toAnnual Reviews content online,including:

Other articles in this volume Top cited articles Top downloaded articles Our comprehensive search

FurtherANNUALREVIEWS


2/28

Climate change:changes in globalclimatic conditions,e.g., temperature,precipitation, andfrequency of extreme

events such as stormsand droughts

Adaptive evolution:evolution via naturalselection in whichindividuals withphenotypes of highertness pass on moregenes to the next generation

Diapause: periodof suspendeddevelopment triggeredby environmental cuesthat occurs in many insects and otheranimals

Photoperiod: amount of light versus dark during a day,dependent on latitudeand time of year, andinuential in biologicalclocks

INTRODUCTION Global temperatures and patterns of precipita-tion are rapidly changing (53). Because theseenvironmental conditions have strong effectson most organisms, it is not surprising that cli-matic changes are inuencing the physiology,behavior, abundance, and distribution of many

species. In contrast to such ecological effectsof climate change, genetic effects of climatechange have been less well studied, althoughthere have been calls to change this (29, 82,135). Recent research results in ecological ge-netics andadvances in quantitative genetics andgenomicsareprovidinginformationonhowcli-mate change may have genetic consequences,but there are large gaps in our knowledge of thelikelihood and rate of adaptive geneticchanges,of the roles of regulatory and epigenetic effects,

and of the evolution of plasticity in providingrapid selection responses, and more generally in our understanding of the genetic architec-ture of adaptive evolution.

Evidence is accumulating that climatechange can cause genetically based adaptiveevolution in traits such as body size (37),thermal responses (62), dispersal (48, 124),and diapause/reproductive timing (35). Weare now starting to uncover the genetic basisof some of these traits, but whether evolution

in these traits is controlled by many inde-pendently acting genes of small effect or by fewer key regulatory genes within genetic andmetabolic networks remains an open question.Evolution can be caused by selection acting onstanding genetic variation, but there is also theintriguing possibility that climate change cancause heritable epigenetic changes, potentially serving as an alternative and rapid mode of evolution (125). Although evolution couldpotentially rescue populations from the effects

of climate change, there is not yet evidencethat this will commonly occur and thereby cir-cumvent a mass extinction and loss of geneticbiodiversity. In fact, a recent meta-analysispredicted major losses in genetic diversity fornorthern plants owing to climate change (1).

Here, we review how climatic conditionsand changes in these conditions can inuence

genes,howthegenetic effects of climate changcan be studied, and what the results of sucstudies might indicate about the genetic basiof evolution. We only briey cover quantitativegeneticandothermodelsaswellasevidencecollected so far in support of evolutionary responses to climate change, as this informatiohas been recently reviewed (40, 49, 112). Thesemodels are being applied to understand evolutionary processes and highlight the evolutionary responses needed to ensure persistence opopulations and species under climate changeas in the case of spawning salmon (107) anpine/birch trees (67). Monitoring of adaptivgeneticresponses to environmental change(44)and approaches to study the genetic basis oadaptive evolution in plant systems have alsbeen recently reviewed (3). Here, we focus orecent attempts to understand the underlyinggenetic basis of evolutionary responses to clmate change. We present a conceptual modeof the genetic basis of climate change adaptation, give examples of recent research, outlinapproaches to studies in this area, describe thusefulness and limitations of these various approaches, and point out areas out where futurresearch is likely to be most fruitful. A goal this review is to investigate how research othe genetic basis of climate change adaptatioadvances our understanding of the process oevolution in natural populations.

SELECTION TO EXPLOIT CONDITIONS OR TOLERATESTRESSES A general framework for depicting how organisms may evolve in response to variochanges in climate is given in Figure 1 . In thisframework, changes in climatic conditions

such as temperature, are separated from cuethat indicate conditions such as photoperiodOrganisms perceive the changes in conditioneither directly or through matching cues tonew conditions. For example, when the cue iphotoperiod, it remains the same with changing climatic conditions, but the way organismrespond to the cue is different (13). This poin

186 Franks Hoffmann


3/28

Response

Detection of change

Other cues(e.g., photoperiod)

Climate changecues

(temperature,moisture, CO 2)

Behavioraladaptation

Life historyadaptation

Physiologicaladaptation

Increased growth rate, distribution,abundance

Persistence of population despite loss of tness

Adaptation throughbehavioralavoidance

Adaptation throughlife historyavoidance

Adaptation throughphysiological

resistance

Stress response

Detectionof stress

Climate changecues

(temperature,moisture, CO 2)

Other cues(e.g., loss of tness)

a b

Figure 1 A framework for considering the direct evolutionary responses of organisms to climate change. Populationsmay be faced with (a) opportunities to take advantage of favorable climatic conditions for expandingdistributions or (b) increasingly stressful conditions in which extinction is possible. Evolutionary changes inthese situations may involve altered ways of detecting and responding to environmental conditions, leadingto changes in life history traits, physiological resistance levels, and migration.

is illustrated by a recent study showing that inpitcher plant mosquitos, circadian clock genes

and photoperiod response genes are linked, but selection can act to break down their geneticcorrelation and allow the cue and responsepathways to evolve independently(12).A recent model has shown that activities stimulated by environmental cues are likely to evolve with cli-mate change, with the outcome highly variableand dependent on the effects of the changes onthecues, responses,andtheir interactions (83).

The climatic changes detected by organismsact as agents of selection. Organisms evolve

in response to climatic changes in one of twogeneral ways: evolving to take advantage of thenewconditions by exploitingnovel or increasedresources (Figure 1 a ) or evolving to toleratenew conditions to which the population isnot currently optimally adapted (Figure 1 b ).Organisms can evolve to exploit new resources

by expanding their range and/or the periodacross which they are active. Most animal

range shifts correlate with climate and show expanding ranges at higher latitudes (123) andinto high elevation areas in animals (6, 87)and plants (71). Geographic expansions may lead to selection for increased dispersal to takeadvantage of favorable conditions (48). Shorterand milder winters in temperate climates canselect for earlier owering in plants and earlierarrival of bird and insect migrants, particularly at temperate and boreal latitudes (97). Thiseffect of increased season length has changed

the migration and breeding patterns of many species (28, 85, 97, 130).

On the other hand, populations are alsoexpected to encounter increasingly unfavor-able conditions (Figure 1 b ) associated withtemperature extremes, ocean acidication, andextreme events, such as droughts, res, and

www.annualreviews.org Genetics of Climate Change Adaptation 187


4/28

Phenotypicplasticity: theexpression of adifferent phenotype by the same genotype in adifferent environment

storms, which can inuence species distri-butions (140). Extreme conditions can select for increased resistance to stressful conditionsand/or ways of avoiding extremes, such as ear-lier owering (35). These effects may be direct,as in the case of increased resistance to drought or heat stress, or indirect, such as when a reduc-tion in food supply is countered by switching toanother food source, as inDarwinsnches(42).Increasedseasonlengthcanpotentially increasetness by providing more time for resource ac-quisition in some species but decrease tnessin others. For example, increased spring tem-peratures can lead to early snowmelt in alpineareas, expanding the growing season but alsosubjecting some overwintering plants to lethalfrost, with warming counterintuitively select-ing for increased cold tolerance (52). Indirect effects can also occur via changes in sex ratio, which can be altered in species such as turtlesin response to changes in temperature means as well as temperature variability (89).

Evolutionary changes to exploit or toleratea resource can occur through behavioral traitssuch as migration (103), life-history traits suchas diapause (13), and physiological traits suchas water-use efciency (33) (Figure 1 ). For in-stance, in pitcher plant mosquitoes there is anevolvedchange in response to photoperiod that allows mosquitoes to take advantage of longerfavorable breeding conditions (13). As well asresponding to altered seasonality, populationsmay also respond to increases in CO2 and re-gional increases in precipitation when adapt-ing to favorable effects of climate change. Forexample, Arabidopsis thaliana plants raised forve generations under CO2 concentrations of 700 ppm evolved to take advantage of this in-creased resource and showed higher seed pro-duction than control lines (132). An increase inthe frequency of extreme climatic events suchas droughts could select for either escape or tol-erance strategies (33).

These responses reect the direct effects of climate change, which are the focus of this review. There are several indirect effects beyondthe scope of this article that nevertheless may have important inuences on genetic responses

to climate change. These include alteredselection pressures when climate change affecbiotic interactions, triggering adaptive changeincompetitiveability or parasite/predatorresis-tance,andadaptivechangesinhostshifts,allowing organisms to evade biotic stresses (98). Clmate change can also indirectly inuence evolution by altering patterns of hybridization as consequence of shifts in species distribution with important genetic consequences (38).

EVOLUTIONARY MECHANISMSPerhaps the simplest way that climate changcan inuence the genetic constitution opopulations is shown in Figure 2 a . Supposethat there is a particular allele ( ) at a locuinuencing a trait such as thermal toleranceSuppose also that individuals carrying thallele have an increased tolerance, improvintheir tness (ability to survive and reproduceat high temperatures. Any increase in thermaextremes over time should then favor alle . To understand and predict the increase inallele frequency under this simple model, thalleles favored under climate change need tbe identied, along with their effects on tnesin different climatic conditions. Organismmay also respond to climate change throughphenotypic plasticity rather than evolution(31). However, in this case there would not be agenetic change in the population because plasticity involves the same genotypes expressindifferent phenotypes in different environments(114), in contrast to evolution, which involvechanges in allele frequencies. It is also possibthat climatic changes, particularly increases ithe variances of climatic conditions, could inuence the evolution of phenotypic plasticityIf variation in the degree of plasticity (rathethan variation of the trait itself) is geneticallbased, alleles leading to increased plasticicould be favored with increased climat variation if this allowed organisms to bettematch their more variable environment (78).

When climate change causes evolutiothrough shifts in allele frequencies, allelchanges do not act in isolation but need to b

188 Franks Hoffmann


5/28

Temperature

W

d u e t o

Selection

Time

T e m p e r a t u r e

Climate change

Time

F r e q u e n c y o f

Evolution

Natural environment

Protein network

Metabolic network

Phenotypic variation

Selection

Change in allelefrequency

Climate change

Maternal environment

Genenetwork

+

+

a

b

Figure 2Genetic effects of climate change adaptation. (a) With evolution, the change in climate results in changes inallele frequencies. This can occur via natural selection: Suppose that the tness of individuals carrying anallele increases with some climatic factor such as temperature. This means that selection on increases with increased temperature. Suppose that temperature increases with time. This climatic change should thenlead to an increase in the frequency of the allele, resulting in an evolutionary change via natural selection.(b) Allelic changes are embedded within networks. Allelic changes do not occur independently of otherchanges; combinations of alleles within gene networks may be required to produce adaptive phenotypes (90). These networks are affected by environmental and maternal inputs, and in turn inuence protein andmetabolic networks, although there are feedback loops and multiple points of environmental inputs.Selection acting on phenotypes therefore often inuences allele frequencies at a specic gene (red arrow)only indirectly.



6/28

Maternal effect: theeffect of maternalresources orenvironment on thephenotype of offspring

Resurrection studies: comparingphenotypes and/orgenotypes of offspringof ancestors anddescendants undercommon conditionsto detect evolutionary change

considered within a gene network and withinthe context of environmental effects and thecomplex way that genotypes map onto pheno-types (Figure 2 b and below). Allelic changesat a locus inuence only one component of agene network; this network also depends onmaternal effects as well as the environment anindividual experiences. Environmental effectsinclude plastic changes such as thermal accli-mation that can be triggered when temperatureextremes inuence the expression of particulargenes. Protein and metabolic networks are theresult of the gene network as well as furtherenvironmental inputs, and these in turn canimpact thegene network, e.g., by affecting generegulation. When genetic response networksare inuenced by environmental conditions,such as temperature or CO 2 level, the networkscould potentially facilitate adaptation by allowing for rapid responses to the changingconditions. However, if the genetic responsenetworks are inuenced by factors, such asphotoperiod, that do not change with climaticconditions, then a network could potentially become out of sync with new conditions, andadaptive changes would require evolutionary shifts that alter the structure of the network (14).

APPROACHES AND TECHNIQUES The genetic basis of evolutionary adaptation tostressful conditions related to climate change isstill poorly understood (108). Although moreand more genomes are being sequenced andannotated, patterns of molecular evolution arestarting to emerge across gene families, andknockout studiesarehelping to indicate numer-ousconnections betweengenes andtraits, thereremain large gaps in identifying the genetic ba-sis of adaptive evolutionary shifts to different climatic conditions. This issue can be explored with a variety of experimental approaches andgenetic techniques that can be broadly dividedinto those applicable to natural populations andthose applicable to experimental populations( Table 1 ). The source material for studies of natural populations cancome from those under

different climatic conditions, such as elevatioor latitudinal gradients, or from resurrectionstudies, in which ancestors and descendants inatural populations that have experienced climatic changes over contemporary time. Ancestors and descendants can also be compared iexperimental evolution studies, which allow thgeneticbasis of evolutionarychangeunder con-trolled conditions to be determined.

Comparing populations naturally occurringunder different conditions, includingclines, is aclassic technique of ecological genetics (27). gene ow among populations is limited, populations may become locally adapted to thclimatic conditions experienced. Experimentssuch as reciprocal transplants, used to determine the extent of local adaptation can also bapplied to help predict evolutionary responseto climate change. For example, Etterson &Shaw (31) found local adaptation butevolutionaryconstraints causedbygeneticcorrelations inan annual plant occurring in different climatiregions of the midwestern United States.

One of the most powerful ways to examinevolutionary changes in natural populations ito collect propagules of individuals before anafter a change in conditions and compare ancestors and descendants reared under commonconditions (34, 35). The advantage of this tech-nique, known as the resurrection approach, ithat it canshowa denitiveevolutionarychangein a natural population, but the disadvantage ithat thus far the technique has been possiblonly in rare circumstances ( Table 1 ). Thereis now, however, an ongoing effort to build collection of seeds that will make it possible apply the resurrection approach to detect evolution in a variety of plant species (99). Witthis approach, ancestors and descendants cabe compared to help elucidate the genetic basiof evolutionary change in natural populations

Temporal changes have also been exploiteto examine morphological evolution connectedto climate change. Body color in tawny ow(Strix aluco) in Finland has changed, most likelas a consequence of altered selection associate with snow cover in winter (62). Morph coloin this species has a high heritability (80%

190 Franks Hoffmann


7/28

Table 1 Methods for isolating genes involved in adaptive genetic responses to climate change, their potential advantages,and their limitations

Source material Description Advantage Limitation Reference Methods based mostly on comparisons of natural populations

Clinalcomparison

Comparisons of populationsfrom along clines

Possible to collect dataimmediately, takesadvantage of past evolutionand local adaptation

Not always possible todetermine if patternsreect climate change orother factors

118

Natural evolution Comparisons based on changesin natural populations acrosstime

The only source material in which populations haveactually adapted incontemporary time tochanges in climate

Often difcult to ndnatural examples of rapidevolution

36

Genome scan of populations

Population comparisonsinvolving a large number of markers to determine whichmarkers are moredifferentiated than expectedfrom neutrality

Relatively easy to apply, canuse a number of different types of markers, allows adirect comparison betweeneffects of selection andpopulation processes

Differentiated marker may be distant from markerunder selection dependingon linkage disequilibrium

102

DNA sequencecomparison of naturalpopulations

DNA hybridization onmicroarrays or othertechniques to identify highly diverged areas of the genome,often involving cline ends

Provides an unbiasedassessment of parts of thegenome involved in adaptivedivergence (within thetechnical limits of theapproach used)

Can be difcult to link toadaptive phenotypic variation; differences may also be related to historicalprocesses

126

Known geneticpolymorphisms

Follow polymorphismsconnected to climateadaptation across time

Can indicate changes inpolymorphisms with knownadaptive functions

Polymorphisms consideredmay only have minoreffects on traits; ignoresmost of genome

128

Knownmorphological

polymorphisms

Follow changes in phenotypicmorphs with a known genetic

basis across time

Morphs are often easily related to adaptive

functions, as in the case of changes in pigmentation

Only applicable to a specicclass of polymorphisms

62

Methods based mostly on comparisons of manipulated populations Articial

selection andexperimentalevolution

Traits related to climatechange adaptation selecteddirectly (articial selections),or populations are placed inenvironments simulatingclimate change effects(experimental evolution)

Traits can be accurately dened, selection pressuresset, and crosses andsequence comparisons usedto assess the genetic basis of selection reecting naturalenvironments; can assesspotential rates of adaptation

Limited by base populationfor selection, may not reect intermittent selection and tradeoffs,depends on species withshort generation time

7

Candidate genecomparisons

Sets of genes that arecandidates for adaptivedivergence considered alonggradients based on knownpolymorphisms or DNA sequencing

Provides a direct link toparticular genes andpolymorphisms; effects ontraits can be conrmedthrough functional analysis

Can be difcult to isolatethe critical polymorphisms,particularly if they are inpromoter regions or if regulatory elements areinvolved; approach willmiss many important genesnot characterized

69

(Contin



8/28

Table 1 ( Continued )

Source material Description Advantage Limitation Reference Transcriptome

comparisonsGene expression microarrays(can also be used for sometargeted genes)

Identies genes and genenetworks that aredifferentiated betweenpopulations and cline endsfor further adaptive studies

Ignores adaptive responsesthat have no effect on geneexpression

46

Quantitative trait locus mapping

Strains are made genetically homozygous and comparedfor quantitative traits

The same set of strains canbe scored for multiple traits,including correlatedresponses, sequenced strainscan be used for a variety of purposes, covers wholegenome

Strains are typically inbredto make them homozygousbefore sequencing, whichmeans that mapping may partly relate to effects of inbreeding depression;adaptive changes may havea different genetic basis,particularly if evolutionacts as a lteringmechanism; difcult forspecies with longgeneration times

86

Associationmapping

Genetic markers are compared with quantitative traitsassociated with climatechange adaptation

Undertaken in outbredpopulations, does not depend on short generationtimes, covers whole genome

Most signals obtained whenmultiple markers available;can be biased towardsdetecting genes of largeeffect; proximity to geneticpolymorphisms affectingtrait depend on markerdensity

11

and crosses suggest a simple genetic basis witha brown morph dominant over a gray morph.

In the past, there has been strong selectionagainst the brown morph over winter, but thishas weakened, and the brown morph has be-come much more common over the past threedecades, increasing from 20% or less to almost 50%, although the exact reason for the tnessadvantage of the brown morph remains un-clear. Body color has also been implicated inthermal selection in periwinkle snails ( Littorinaobtusata), which have a shell color polymor-phism with frequencies varying along the in-

tertidal rocky shore and evidence for selectionbased on direct manipulations of shell color(100).

This temporal approach can be combined with clinal selection. For instance, there is clinal variation in the frequency of the common alle-les at the alcohol dehydrogenasegene in Drosophila

melanogaster , and the clinal pattern has changedover a periodspanning> 20years; this change i

consistent with thermal selection on the alcohodehydrogenase polymorphism (128). The sameapproach continues to be used to explore selection on inversion polymorphisms in Drosophilspecies (109).

For individuals that can be raised undelaboratory conditions and that have short gen-eration times, it is possible to apply articiselection or experimental evolution. Witharticial selection, individuals are selected fobreeding on the basisof traits related to climate

change adaptation, such as thermal tolerancedrought tolerance, and dispersal ability (108)In experimental evolution studies, conditionare manipulated to represent changes inclimatic conditions (such as increased temperature or CO 2 levels), and the populationare allowed to evolve in response to the

192 Franks Hoffmann


9/28

Quantitative trait locus (QTL)mapping: a technused to map genetregions associated variation in traits

interest Candidate gene:a gene putatively associated with aparticular trait,phenomenon, orevolutionary chanon the basis of gecomparisons orfunction

Massively parallelsequencing (next-generation sequencing):techniques (Illumi454, SOLiD) in wDNA is sheared inmillions of smallfragments that aresimultaneously sequenced

Genome scan:a technique of genotyping individat many loci

throughout thegenome, oftenaccomplished thromassively parallelsequencing

Single nucleotidepolymorphisms(SNPs): loci show variation at singlenucleotides, used genetic markers

F ST : a measure inpopulation geneticgenetic differentiaamong populationbased on single ormultiple loci

conditions (7, 26). For example, Burke et al.(16) manipulated temperature conditions in which Drosophila were raised and identiedmany genes that changed expression patternsunder common conditions after evolving underelevated temperature. Functional analysisof these genes suggested many that may beconnected to thermal tolerance. An advantageof this approach is that treatments or selec-tion criteria can be precisely dened, and adisadvantage is that changes may not reect patterns of evolution under climate changein natural populations ( Table 1 ) in whichstressful conditions occur sporadically and un-evenly within an area. In some cases, it may bepossible to undertake selection directly in theeld, as in sticklebacks (Gasterosteus aculeatus )transplanted from marine to colder freshwaterenvironments; the transplanted populationsevolved an increase in cold tolerance of morethan 2 C despite only two rounds of selection(5), potentially allowing these populations tocounter increased levels of thermal variability.

All of these sets of source material (collec-tions from natural populations over space ortime, or individuals from articial selection orevolution experiments) can be combined witha variety of genomic and transcriptomic tech-niques to determine the genetic basis of evo-lutionary change ( Table 1 ). To determine thegenetic basis of variation in a trait, the standardapproaches are quantitative trait locus (QTL)mapping or association mapping, both of whichconnect phenotypic variation in one or moretraits to genetic variation at a number of loci(75). QTL mapping requires the use of recom-binant inbred lines and can only map traits to acoarse scale but requires fewer individuals thanassociation mapping. Association mapping canlocate genes more precisely and does not de-pend on the development of inbred lines but requires more individuals and may be biasedbecause of population structure (138), althoughstatistical approaches can be used to help ac-count for this (60). Both QTL and associationmapping can be used to nd a genes under-lying trait variation, but neither is designed toexamine evolution directly; although variation

at a particular locus might explain variation ina trait, this does not prove that the locus is nec-essarily involved in evolutionary responses innatural populations.

To identify the genetic basis of evolutionfollowing climate change, sets of source ma-terial from populations under different cli-matic conditions or before and after naturalor articial climatic changes can be comparedat the level of the whole genome, the tran-scriptome, or individual candidate genes. By using massively parallel sequencing (such as454 pyrosequencing or Illumina sequencing)or genome scans [genotyping with many sin-gle nucleotide polymorphisms (SNPs) or othermarkers], many genes throughout the genomecan be assessed for variation and comparedamong populations (30, 93, 111, 117). For ex-ample,Prunier et al. (102)usedgenome scans of black spruce ( Picea mariana) from populations varying in temperature and precipitation toidentify SNPs. Genes that had outlier FST val-ues were located in exons, had nonsynonymouspolymorphisms, showed signicant regression with climatic variables, had functional annota-tion consistent with climatic responses, wereconsidered prime candidates for adaptation toclimatic variation, and could potentially show responses to climate change. Another exampleinvolves theAntarctic clam, Laternula elliptica, apotential sentinel species for monitoring oceanacidication effects because it lives in a low cal-cium carbonate environment, and acidicationis expected to affect shell formation. Through454 sequencing of mantle tissue, a number of genes likely to be connected to shell deposi-tion were identied particularly through mak-ing connections to model mollusk species suchasmussels, providinggene targets forfunctionalanalysis and potential future monitoring (22).

Genomic comparisons and genome scanscan provide useful information on differencesamong populations (particularly for species with a reference genome), but much of thegenome is not expressed. By focusing ontranscribed genes or on the full transcriptome,it is possible to narrow the set of genes of interest to those actually expressed as well as



10/28

RNA-seq:a technique fortranscription prolingof expressed genes by sequencing andquantifying products

that cDNA derivedfrom mRNA

to evaluate differences in levels of expressionunder different conditions. Analysis of tran-scribed genes involves extracting mRNA andmeasuring expression level. This can be done with techniques such as quantitative real-timePCR for a small number of genes, microarraysfor a large number of genes, or massively paral-lel sequencing of expressed genes (RNA-seq) at the scale of the whole genome. One particularadvantage of examining gene expression in aclimate change adaptation context is that not only can different source material originatingunder different conditions be compared, but also the climatic factor can be experimentally manipulated and expression measured underthe different treatments. For example, individuals could be collected from a warmer anda cooler area along a thermal cline and geneexpression measured at both warm and cooltemperatures. Genes that differed in expressionbetween the source populations and between warm and cool temperature treatments might be particularly likely to play a role in thermaladaptation and evolution following changes intemperature, particularly if functional anno-tation points to connections with mechanismsinvolved in temperature or stress tolerance.Genome scans and genome-wide expressionproling have been highly successful in helpingto elucidate the genetic basis of toleranceto high altitude conditions in vertebrates(20).

Tests such as the McDonald-Kreitman test compare the ratios of synonymous to nonsyn-onymous substitutions at polymorphic sites tolook for genomic signatures of selection (79).Such tests can be used to help determine if past climatic changes may have left signatures of selection and are starting to be used in a variety of contexts, including adaptation of corals andDrosophila to thermal environments (119, 131).Identication of outlier FST values has alsobeen useful in identifying genes involved inlocal adaptation and adaptive evolution, withrecent advances making this technique evenmore effective (68).

These studies and comparisons could be fur-ther extended to include information on trait

variation and trait interactions within a phylogenetic framework (112). So far one study haconsidered geneticvariation that is phylogenet-icallycontrolled, showing that genetic variationfor desiccation resistance is very low for sesitive rainforest species of Drosophila, whereasmore-resistant widespread species tend to havhigher levels of variability, a pattern that remained signicant when species association were controlled for phylogeny and also evdentwhenspecieswerecomparedforcoldresistance (63). As argued by Salamani & Bell (11phylogenetic analyses could be extended to encompass variability among populations andalsinteractions among traits, particularly whenpopulations differ substantially in their thermaresponses, as in the case of the copepod Tigrio- pus californicus (64).

IDENTIFYING CANDIDATEGENE SETS There has been substantial progress in recent years identifying structural and regulatorygenes that are potentially involved in adapting to climate change. This work has mostlproceeded through functional analysis of specic genes using under- and overexpressioandthrough broad transcriptomic andgenomicscans. Despite these efforts, there has beemuch less progress in identifying natural varation in genes linked to climate change adaptation, which is likely to require adaptation ta suite of environmental alterations, includinchanges in seasonality, thermal conditions, water availability, and biotic interactions.

In Drosophila, early lists of candidate gene were compiled for thermal tolerance on thbasis of candidate gene work and transcriptomic studies (50). Additional genes and genregions have subsequently been identied (2324, 91, 106), and there has been some progresin comparing candidate genes across studiealthough results are mixed. Rand et al. (106 worked with D. melanogaster and successfullused QTL mapping to isolate the shaggy generegion of the X chromosome and demonstratethat this region is involved in differentiatio

194 Franks Hoffmann


11/28

of different temperatures. The alleles identi-ed were also differentiated in lines selectedfor high-temperature knockdownand in a sam-ple of populations from a natural thermal clinein North America, but not in a larger samplefrom Australia. These results point to the waysin which selection experiments can be used tond candidate genes relevant in nature. In thesame way, experiments on laboratory thermalselection in D. melanogaster have implicated the Hsr-omega gene as being important in thermaladaptation (58), andthese results have also beenlinked to clinal variation in natural populations(25).

Genomic comparisons can increase the list of candidates rather dramatically. Comparisonsof tropical and temperate populations of D.melanogaster from Australia suggest a lot of ge-nomic regions that are differentiated betweenthese populations and most likely under selec-tion (66), and this also matches genetic differ-entiation fora numberof quantitative traits (51,115), despite Australia being colonized by thisspecies for just over 100 years. Some of the ar-eas of substantial genomic differentiation areassociated with a cosmopolitan inversionon theright arm of chromosome III (66), which showsa pattern of clinal differentiation that has sub-stantially shifted in the past 20 years so that allpopulations have become more tropical in theirconstitution with respect to this chromosomalregion (2, 128). Populations from the ends of climatic clines in Australia and North Americaarealso differentiated forclasses of transposableelements expected to be adaptive, which show stronger differentiation than transposable ele-ments considered to be neutral (41).

Genomescreens arestarting to be employedto identify areas of the genome connected toclimate adaptation in animals. Redband trout (Oncorhyncus mykiss gairdneri ) from six mon-tane andsix desert environments were screenedfor 69 SNP polymorphisms, and ve polymor-phisms differentiated by climate (temperature) were identied, whereas the others appearedto show neutral patterns (88). Because thesepolymorphisms sampled only a small part of the genome, the results suggest that multiple

loci are involved in thermal adaptation in thisspecies. Across 61 human populations, SNPshave been identied that show strong associa-tions with climate (43), including those associ-ated with pigmentation.

Several screens of plant populations fromdifferent climates are starting to produce setsof candidate genes for climatic adaptation. Inboreal black spruce ( Picea mariana), a survey of more than 500 SNPs in genes potentially related to precipitation and thermal variabil-ity across 26 populations led to the eventualisolation of 26 SNPs in 25 genes that showeda strong association with the climate variables(102) These genes have a variety of putativefunctions, including phenology,growth, repro-duction, wood formation, and stress response,many of which make sense in a climate changeadaptation context.

A broad genome screen of SNPs and ageographically diverse set of almost 1,000accessions of A. thaliana across environmental variables produced numerous candidate genespotentially involved in climatic adaptation (43).Signals of adaptive shifts were tested further by an enrichment of functional nonsynonymouschanges and by growing plants in a commonenvironment and then testing whether countsof putative adaptive alleles could predict tnessin this environment. This analysis showed astrong correlation between tness in the com-mon environment and the number of favoredalleles, conrming the validity of the initialscreen. In a different set of experiments with Arabidopsis , plants from multiple inbred lines were grown in four sites differing in climate,and SNPs at each location were associated with survival and reproductive output (32);SNPs with substantial effects were identied,and these proved to be locally abundant at twoof the sites. The absence of strong selectivesweeps suggested that local alleles were favored via selection on standing variation rather thanthrough sweeps. Alleles affecting reproductiveoutput were locally common (locally selected),andthose affectingsurvival were more commonacross the species range, suggesting survivalalleles were widely favored at multiple sites.



12/28

Hsp70: one of theheat shock proteinsfound in many organisms; genescoding for theseproteins are typically

upregulated whenorganisms are exposedto heat or otherstressors

Several candidate loci involved in adaptationto different temperature and precipitationregimes were identied for future study.

Transcriptomic comparisons have usually involved a single population exposed to differ-ent climatic conditions to identify genes andgene ontogeny classes that tend to be dif-ferentially expressed and may point to candi-dates. Gene discovery from these efforts hasproven challenging given the sheer number of genes that typically show altered expressionpatterns that may be indirectly related to thetraits of interest (129). Recently, these types of studies have moved to consider multiple nat-ural/selected populations or lines when rearedunder the same conditions and challenged by the same sets of stressful conditions. For ex-ample, Levine et al. (72) compared the plastic-ity of expression in D. melanogaster from tropi-cal and temperate Australian populations whenreared under warm and cool conditions, andthey showed that plasticity in the expressionof genes differed depending on origin, withgreater expression of genes in the thermal homeenvironment of the population. Cassone et al.(17) found that lines with one arrangement of a chromosome inversion polymorphism in Anopheles gambiaeexhibiteda higher levelofup-regulation of genes from several pathways fol-lowingheat stress than lines with thealternativeform; this could account for the higher level of heat/aridity resistance in one of the arrange-ments but could also lead to trade-offs if thereis an increase in expression of genes unrelatedto the provision of stress protection. By link-ing changes in expression across multiple pop-ulations to environmentally induced changes inexpression, it is more likely that candidate locifor adaptive responses can be identied, par-ticularly when multiple stresses are considered(18).

Nevertheless, linking gene expression pat-terns across populations or lines with adaptivechanges is not straightforward. Changes inspecic genes may be restricted to a particularlife cycle stage; in D. melanogaster , variation inhsp70 expression levels among lines correlates with heat resistance at the larval stage, but at

the adult stage no association is evident (57Expression changes may also be unpredictablSouthern populations of the Atlantic killis( Fundulus heteroclitus ) are adapted to warmconditions and differ in heat shock proteiexpression from the cold-adapted northernpopulation, but there is no consistency acrosthe heat shock genes as to whether expression levels are increased or decreased in thsouthern population (46).

A challenge in transcriptomic studies of candidate genes is to move beyond simply describing patterns of up- and downregulation ogenes, which can depend on background levels (113). This can be achieved by linking paterns to those evident from other omics technologies, particularly metabolomics (129), aninterpreting changes within a network context (see below). Once networks are knowon the basis of studies of environmental responses, geneknockouts,andotherapproachesresearchers can begin considering the effects ogenetic variants at different phenotypic levels

Apart from genome and transcriptomescans, some very large genome-wide mappinefforts are starting to provide a detailed picturof the genes associated withchanges in traits responding to environmental cues. In A. thaliana,an assessment of genome-wide diversity acromore than 400 accessions planted in differenclimates and seasons led to the identicatioof 12 QTLs that affect owering time in aseason-location specic manner (73). For Dmelanogaster , genome-wide deciency mappinghas recently been used to identify 19 QTLinuencing heat resistance (120), DNA-DNAhybridization between multiple selected ancontrol lines was used to identify polymorphiregions responding to selection for desiccatioresistance (121), and next-generation sequencing of pooled samples was used to identify SNmarkers associated with novel thermal andpho-toperiodic conditions (93).AlthoughDrosophillines are typically measured under highly dened assays in laboratory environments, recen work points to ways in which identied QTLcan be linked to performance under differeneld conditions (74). Genomic approaches ca

196 Franks Hoffmann


13/28

Methylation:the addition of amethylation groupexample, to cytosi which is an impormechanism of

epigenetic regulat Vernalization: lithrough a cold per(winter), which acan important signatime of year in maplants

also be used for nonmodel organisms whenthere is a reference genome available from a re-lated species, as in the case of heat shock genesin Arctic charr, which were identied fromassociation mapping following comparisons tothe Atlantic salmon genome (104).

To summarize, a number of approaches arenow available to isolate candidate genes involved in climate adaptation across model andnonmodel species. Genome scans and tran-scriptomic studies are starting to produce longcandidate lists. However, moving from lists to validated candidates remains challenging andrequires studies of model organisms in whichgenetic manipulations are possible.

NETWORKS AND REGULATION Changes in genetic networks may play a largerole in contemporary evolution and climatechange responses. Traits important in climatechange responses, such as the timing of ow-ering (133) or stress responses (129), are of-ten controlled by genetic regulatory networks. These networks involve multiple genes andgene products, transcription factors, and pro-teins that interact with each other and with sig-nals from the internal andexternal environment to produce a phenotype suited to given condi-tions (136). Changes in specic genes withingenetic networks inuence the expression of genes, and changes within biochemical pathways ultimately dictate how genetic changes in-uence phenotypes. In some cases, the connec-tion between changes in genes and phenotypiceffects involved in climatic responses may berelatively simple. For instance, an increase inthe amount of Hsp70 produced by Hsp70 genesmay set the level of protection from denatura-tion during heat stress and inuence survivalin a range of organisms. However, even in thiscase a geneticregulatory network inuences theexpression of heat shock proteins through vari-ous interacting transcriptional factors that bindto the promoter region of Hsp70 genes to in-uence expression (94). Moreover, alternativesplicing, in which RNA transcripts arearrangedin multiple ways so that a single gene can code

for multiple proteins (15), can inuence the tis-sue expression of heat shock genes such as Hsr omega from D. melanogaster , which inuencesthe repression of protein synthesis (59).

Most adaptive changes in response toclimate change occur within a regulatory network of genetic effects, and processes suchas alternative splicing and the binding of tran-scription factors as well as posttranscriptionalregulatory mechanisms and the expressionand interaction of other elements could bekey mechanisms of evolutionary responses toclimate change. There is now a much greaterappreciation of the different levels of geneand metabolite regulation that mediate stressresponses (116). It is no longer consideredparticularly useful to split geneticvariation intosimple structural and regulatory categories.Changes in structural components of genes canaffect expression, and regulatory elements now encompass a range of processes, including cis -acting control elements, transcription factors,and metabolites, whereas regulatory processesinvolvenotonly transcriptional control but alsoposttranscriptional modication and controlof DNA through methylation (61, 129).

Some of these networks and interactions arequite well understood and can be linked to spe-cic genetic variants. For instance, the pathway controlling owering time and vernalization inplants (discussed below) involves the integra-tion of a number of pathways associated withdifferent environmental cues (134). Variationin abdominalpigmentation in Drosophila, whichpotentially inuences resistance to multiplestressors (96), is affected by a well-characterizednetwork of genes that includes regulatory ele-ments that respond to environmental cues andthereby inuence plastic responses (39).

When a large number of genes with vari-ation in expression patterns are embedded incomplex networks and there are strong pat-terns of correlations among the expression of thegenes,itmaybedifculttoextracttheeffectsof specic polymorphisms on traits involvedin climate adaptation. Expression changes ingenes upstream in networks might have largeand multiple effects on traits, but expression



14/28

Epigenetics:the study of generegulation andinheritance viamechanisms otherthan changes in gene

sequence, such as themethylation of cytosine

changes in these genes may be constrained be-cause they are more likely to have detrimentaleffects on tness. The combined effects of vari-ation in numerous components of networks canmean that the effects of specic genes are lost unless there is a level of control of the naturalgenetic background (92).

Nevertheless, adaptive shifts in traits such assize across gradients canbe inuenced by majorgene effects even when variation within pop-ulations has a complex basis; for example, inDrosophila much of the variation for body pig-mentation seems associated with genetic varia-tion in the expression of the ebony gene (122),even though numerous genes and interactingpathways could potentially be involved in pig-mentation pathways (39).

An important question is whether networks are conserved or whether there arealternative pathways to the same evolutionary outcomes (and whether these are predictable).For instance, for owering, the photoperiodresponse is conserved between Arabidopsis and cereals, but the vernalization response isnot (see below). Another important issue is whether the nature of networks can facilitate orretard evolutionary rates; models suggest that small networks can enhance rates under rapidenvironmental change through increasingthe expression of heritable variation (76). Adaptation to climate change may therefore bemore likely to involve these networks, but thisconcept needs to be tested empirically.

EPIGENETICS: AN ALTERNATIVE MODEOF CLIMATE CHANGE ADAPTATION It is now well established that the environment can inuence gene expression, and thus pheno-type, through epigenetic mechanisms (9, 54).In the contemporary sense, epigenetics refersto any inheritedchanges in the phenotype of anorganism that are not directly due to variationin gene sequence (9, 110). Several epigeneticmechanisms have been established, includingthe methylation of cytosine, modication of

chromatin structure, and alterations in generegulation due to small RNAs (9).

At least in some cases, phenotypic traits cabe passed on from parents (particularly the maternal parent) to offspring epigenetically foone or more generations without any changein gene sequence, providing a fundamentalldistinct and potentially very rapid phenotypichangethatisrelevanttorapidadaptationtocli-mate change (125). An extensive set of casestransgenerational epigenetic inheritance is nowknown (54). This includes examples in whicepigenetic mechanisms increase resistance to range of stresses, including thermal extremesin untreated F1 offspring (10, 45). Maternal effects that inuence traits such as resistance theat stress (56) are also likely to often reeepigenetic mechanisms that act across one otwo generations. Epigenetic mechanisms canalso inuence rates of recombination andmuta-tion, leading to genetic changes that are passeto offspring (45). Stressful conditions may leato epigenetic modications that mobilize trans-posable elements, causing major genetic alterationsandrearrangements (137). In these casesepigenetic mechanisms can lead to permanenchanges in traits.

Although it is known that epigenetimodications can play an important role ingene regulation and expression, their role inadaptation to stressful conditions in naturapopulations is not yet clear (9). Epigenetimechanisms passed across a generation thaincrease the tness of offspring under stressfuconditions may prevent populations fromdecreasing in size, losing genetic variatioand becoming extinct. Inherited epigenetimodications that are passed on to offsprinbecause of altered rates of recombination anmutation may permanently inuence pheno-typic variation and tness of populations (125However, the extent to which these modications facilitate persistence and evolution opopulations in changing climates is unknown.

CASE STUDIES To uncover the genetic basis of an adaptivevolutionary change in a quantitative trait t

198 Franks Hoffmann


15/28

a change in climate, we would ideally like tobe able to show that a particular trait (a) isgenetically based and heritable; (b) is underdifferential selection and has different tnessunder different climatic conditions (changes inclimate alter the pattern of selection); (c ) variesgeographically along latitudinal, altitudinal, orothergradients ina wayconsistent with climatic variation; and (d ) has changed in mean value ina population following natural or experimentalchanges in climate. We would want to (e) iden-tify genes and networks underlying variation inthe trait and ( f ) show that allele frequencies of one ormoreof these genes have changed withina population following a change in climate. Allsixofthesecriteriahavenotyetbeenmetwithina single study or system, although some studiesmentioned above have shown one or more of these components. We provide two examplesof traitsowering time and body sizethat have often been linked to climate change adap-tation. In the case of owering time, we areclose to meeting many of the criteria, whereas with body size we are only just starting to reacha very preliminary level of understanding.

Flowering TimeFlowering time is an important trait in plantsandhighly relevant forgenetic adaptation tocli-mate change. Climatic conditions have a strongeffect on reproductive phenology and the re-lationship between owering time and tness(101). Previous studies have shown that ower-ing time meets several of the criteria describedabove to demonstrate the genetic basis of anevolutionary response to climate change. Onestudy(35) found that in the annualplant Brassicarapa, owering time was heritable, early ow-ering plants had greater tness under drought conditions than late owering plants, and av-erage owering time was earlier in plants fol-lowing a natural drought than in plants frombefore the drought when ancestors and descen-dants were growntogetherunder commoncon-ditions. In many other species owering time isheritable (47), is under selection (52), and hasshifted following changes in climate (85).

One feature of owering time that makes it ideal for a study of the genetic basis of evolu-tion under climate change is that a substantialamount of information already is known about genes, pathways, and processes involved indetermining owering time (84, 133). In Ara-bidopsis ,oweringtimeiscontrolledbyageneticregulatory network involving four main pathways: photoperiod, temperature, gibberellin,and autonomous (Figure 3 ) (84). Internal(hormones such as gibberellins) and external(photoperiod, temperature) signals inuencethese pathways in a way that prevents a plant from owering too early or too late. Althoughthis regulatory network is quite complex; in-cludes hundreds of genes, transcription factors,and receptor proteins; and involves variation ingene expressionaswell asepigenetic regulation;

Photoperiodpathway

Autonomouspathway

Vernalizationpathway

Gibberellinpathway

Floral meristemidentity genes

FLC

FT, SOC1

CO FRI , VRN FCA

Figure 3Summary of the owering time genetic regulatory network. Shown are thfour main genetic pathways inuencing owering time in Arabidopsis thalphotoperiod, autonomous, vernalization, and gibberellin. These pathways in concert to regulate owering time. Some of the major genes involved inpathways are also indicated. Red lines indicate suppression, and black arrindicate promotion. For example, the gene FLC suppresses the owering promoters FT and SOC1, preventing owering until FLC is suppressed bgene products from the vernalization or autonomous pathways. The oralmeristem identity genes cause meristem tissue to differentiate into oral rthan vegetative tissue, which causes owering to begin. Evolutionary chain owering time due to climate change could be a result of changes in afrequencies of these owering time genes, changes in their expression orregulation, or changes in other genes with pleiotropic effects on owering



16/28

only a relatively small number of genes appearto vary in the wild and to inuence the ower-ing time phenotype in natural populations (70,118). These are thus prime candidate genes forexamining the genetic basis of owering time variation and evolution across taxa in naturalconditions.

Previous studies with Arabidopsis have foundassociations between owering time, variationsin candidate owering time genes, and climate.One study showed a cline in owering timein Arabidopsis from accessions from southernto northern Europe as well as a differentialeffect of loss-of-function mutations in theowering time gene FRIGIDA across this cline(118). McKay et al. (80) showed that a naturalcline in owering time in Arabidopsis coincided with variation in the owering time gene FLOWERING LOCUS C , which affected bothowering time and wateruse efciency. Li et al.(73) conducted a genome-wide associationmapping study in Arabidopsis and identied 12candidate genes associated with owering time,four of which were correlated with latitudeof origin. Some of the QTLs had previously been identied, including the FRIGIDA locus,but the majority of QTLs mapped to novelareas of the genome. The QTLs that affectedseasonal timing were associated with latitudi-nal variation and affected yield, suggesting animportant role in local adaptation to climaticconditions. Another study with A. thalianafound that genetic variation at owering timeloci inuenced climate niche breadth and that later owering genotypes had more restrictedrange potentials than early owering genotypesdid (4), suggesting that the owering timegenotype will strongly inuence response toclimate change in this species. Flowering timegenes linked to climate conditions have alsobeen isolated in nonmodel plants. In pearlmillet ( Pennisetum glaucum), initially a genomescanwas used to identifya signature of selectionalong a rainfall gradient in a MADS-box gene, PgMADS11, and association mapping was thenused to link polymorphism in this gene to ow-ering time variation in a separate population(77).

It is therefore known that at least in somcases owering time is heritable, is under seletion by climatic factors, varies across climatclines, and can evolve following changes in cmaticconditions.Additionally, candidate genehave been identied that are linked to variatioin owering time as well as to climatic condtions, and the function of many of these geneis known. Further work on owering time ilikely to provide more information on the genetic basis of adaptive evolutionary responseto climate change.

Body SizeBody size has been associated with climachange adaptation and climate variation iboth ectotherms and endotherms (37). In ec-totherms, size variation may show Bergmanclines (increasing body size at higher lattudes/elevations) thought to reect the advantage of large-bodied organisms in cold conditions and reverse Bergmann clines thought toreect adaptation to seasonality in which smaorganisms have an advantage when favorabseasonal conditions for development are shor(8, 21). In endotherms, size variation also ofteshows geographic patterns along climatic gradients, perhaps reecting the energy and wateneeded to maintain body temperature and thesurface area available for heat exchange (37Climate may also inuence size indirectly, sucasbyaffecting theavailabilityandnature of foosources, which dictate selection on body sizin Darwins nches during periods of drough(42). Changes in size in endotherms and ectotherms may have a genetic basis, althougenvironmental effects can be enormous and ooverriding importance in some cases (95).

Size variation can be highly heritable iendotherms and ectotherms, although thiscan depend on environmental conditions (19) The genetic basis of size is always assumto be complex given that a large number ogenes inuence growth rate and developmentand this conjecture is certainly supported bgenetic analyses of Drosophila lines (127), witsize mapping indicating contributions from al

200 Franks Hoffmann


17/28

genomic regions (139). Yet in D. melanogaster ,clinal variation in size (Figure 4 ) acrossmultiple continents (55) is associated with theright arm of chromosome 3 (65). In Australianpopulations, approximately two-thirds of size variation in males maps to this region, whichcontains a large inversion (105) and in whichassociation mapping indicates size genes lo-cated in two peaks. For wing size, at least 10%of the genetic variation is tightly associated with a promoter polymorphism in the Dcagene, which affects cell number (65, 69). Allelesin the Dca promotor region as well as Dcaexpression show clinal variation (Figure 4 ),and there is direct evidence from associationstudies and altered expression studies that increased expression of this gene is associated with decreased size (69, 81). Recent genomicanalysis of Drosophila selection lines and popu-lation comparisons emphasize the role of alleleshifts at multiple loci in changing traits (126),but adaptive changes might occur through only some of these loci, resulting in quite a different genetic basis for traits than indicated throughmapping variation among lines.

Size therefore represents a trait with acomplex relationship to tness and potentially linked to climate change adaptation throughmultiple selective factors. Because size can beeasily measured, it is an attractive trait for rou-tine monitoring in relation to climate change.However, the heritable basis of size shifts hasrarely been examined, and little is known about thegeneticbasis of adaptive variationin size po-tentially inuenced by a complex of genes andregulatory pathways.

CONCLUSIONSSince the modern evolutionary synthesis, it hasbeen a major goal of evolutionary biology touncover the genetic basis of adaptive evolution. The rapid evolutionary responses of at least some organisms to current climate changeindi-cates that studying contemporary evolutionary changes that result from climate change may provide opportunities to advance this goal. Todo so, it is important to combine ecological

0

10

20

30

40

50

60

70

80

10 15 20 25 30 35 40 45 50

10 15 20 25 30 35 40 45 50

10 15 20 25 30 35 40 45 50

A l l e l e f r e q u e n c y ( % )

24

23a

0.000

0.005

0.010

0.015

0.020

0.025

0.030

0.035

D c a e x p r e s s i o n l e v e l r e l a t i v e t o R p L 1 1

b

1.6

1.8

2.0

2.2

2.4

W i n

g a r e a ( m m

2 )

Latitude (S)

c

Figure 4 Associations between latitude and three interrelated variables measured apopulations of Drosophila melanogaster from the eastern Australian coast.(a) Frequency of two indel alleles (237, 247) in the promoter region of thgene (81). (b) Expression of Dca relative to a control gene, RpL11 (69). (c ) W

area of females reared under controlled conditions (55).

approaches to studying responses to climatechange with a variety of techniques in molec-ular and quantitative genetics and genomics.Recent advances, including genome sequenc-ing and transcription proling, help to uncover



18/28

the genetic basis of climate change adaptation.However, future studies need to be groundedin a thorough understanding of the ecologicalcontext of the environmental changes, needto use well-designed experiments, and needto draw on current knowledge of geneticregulation and interactions to avoid shingexpeditions involving enormous amounts of genetic information without clear questions. A better understanding of the genetic basis of adaptation to climate change will address such

topics as the number and relative importance ofgenes involved in evolutionary changes, the degree to which changes in gene regulation resulin evolution, and the role of additional mechanisms, such as epigenetics, in evolution natural populations. Although recent researchhas increased understanding of links betweegenes and traits and how genes vary acrosenvironmental gradients, our understanding ofthe genetic basis of evolutionary responses tchanges in climate is still quite limited.

Transcription proling: a techniquefor measuringtranscription levelsthrough quantifyingmRNA levels at expressed genes

throughout thegenome

SUMMARY POINTS

1. Climate changeis occurring, affecting many organisms, and, at least in some cases, leadingto evolutionary change that results in changed gene andallele frequencies in populations.

2. Studying evolutionary responses to climate change can help us to uncover the geneticbasis of adaptive evolution.

3. Methods of studying the genetic basis of climate change adaptation involve a choice ofsource material (e.g., sampling along latitudinal or altitudinal gradients and before andafter a natural or articial environmental change) as well as a variety of possible genetictechniques(e.g.,genome scans, transcriptome comparisons, candidategenecomparisons,and genetic mapping).

4. Substantial progress has been made recently in uncovering genes linked to traits of adaptive signicance and genes associated with climatic variation. However, much less isknown about genetic changes occurring as a result of climate change.

5. Body size in animals and owering time in plants are two examples of areas in whichfurther research into the genetic basis of climate change adaptation seems particularly promising.

DISCLOSURE STATEMENT The authors are not aware of any afliations, memberships, funding, or nancial holdings thmight be perceived as affecting the objectivity of this review.

ACKNOWLEDGMENTS Jason Sexton provided helpful comments on this manuscript. The work was supported by a facultfellowshipto S.J.F. fromFordham University,a NationalScience FoundationgrantDEB-1120241to S.J.F. and collaborators, and grants to A.A.H. from the Australian Research Council.

LITERATURE CITED1. Alsos IG, Ehrich D, Thuiller W, Eidesen PB, Tribsch A, et al. 2012. Genetic consequences of clima

change for northern plants. Proc. R. Soc. B. In press, doi: 10.1098/rspb.2011.2363

202 Franks Hoffmann


19/28

2. Anderson AR, Hoffmann AA, McKechnie SW, Umina PA, Weeks AR. 2005. The latitudinal cline in the In(3R)Payne inversion polymorphism has shifted in the last 20 years in Australian Drosophila melanogaster populations. Mol. Ecol. 14:85158

3. Anderson JT,Willis JH,Mitchell-OldsT. 2011.Evolutionarygeneticsof plantadaptation. TrendsGenet.27:25866

4. Banta JA, Ehrenreich IM, Gerard S, Chou L, Wilczek A, et al. 2012. Climate envelope modellingreveals intraspecic relationships among owering phenology, niche breadth and potential range size in Arabidopsis thaliana. Ecol. Lett. 15:76977

5. Barrett RDH, Paccard A, Healy TM,Bergek S,Schulte PM,et al.2011.Rapidevolutionof cold tolerancein stickleback. Proc. R. Soc. B 278:23338

6. Beever EA, Ray C, Wilkening JL, Brussard PF, Mote PW. 2011. Contemporary climate change altersthe pace and drivers of extinction. Glob. Change Biol. 17:205470

7. Bell G, Gonzalez A. 2009. Evolutionary rescue can prevent extinction following environmental change. Ecol. Lett. 12:94248

8. Blanckenhorn WU, Demont M. 2004. Bergmann and converse Bergmann latitudinal clines in arthro-pods: two ends of a continuum? Integr. Comp. Biol. 44:41324

9. Bossdorf O, Richards CL, Pigliucci M. 2008. Epigenetics for ecologists. Ecol. Lett. 11:1061510. Boyko A, Blevins T, Yao YL, Golubov A, Bilichak A, et al. 2010. Transgenerational adaptation of

Arabidopsis to stress requires DNA methylation and the function of Dicer-like proteins. PLoS ONE 5:e9514

11. Brachi B, Faure N, Horton M, Flahauw E, Vazquez A, et al. 2010. Linkage and association mapping of Arabidopsis thaliana owering time in nature. PLoS Genet. 6:e1000940

12. Bradshaw WE, Emerson KJ, Holzapfel CM. 2011. Genetic correlations and the evolution of photope-riodic time measurement within a local population of the pitcher-plant mosquito, Wyeomyia smithii . Heredity 108:47379

13. Bradshaw WE, Holzapfel CM. 2008. Genetic response to rapid climate change: Its seasonal timing that matters. Mol. Ecol. 17:15766

14. Bradshaw WE, Holzapfel CM. 2010. Light, time, and the physiology of biotic response to rapid climatechange in animals. Annu. Rev. Physiol. 72:14766

15. Brett D, Pospisil H, Valcarcel J, Reich J, Bork P. 2002. Alternative splicing andgenome complexity. Nat.Genet. 30:2930

16. BurkeMK, Dunham JP,ShahrestaniP, ThorntonKR,RoseMR,LongAD.2011.Genome-wideanalysisof a long-term evolution experiment with Drosophila. Nature 467:58790

17. Cassone BJ, Molloy MJ, Cheng CD, Tan JC, Hahn MW, Besansky NJ. 2011. Divergent transcriptionalresponse to thermal stress by Anopheles gambiae larvae carrying alternative arrangements of inversion2La. Mol. Ecol. 20:256780

18. Chapman RW, Mancia A, Beal M, Veloso A, Rathburn C, et al. 2011. The transcriptomic responses of the eastern oyster, Crassostrea virginica, to environmental conditions. Mol. Ecol. 20:143149

19. Charmantier A, Garant D. 2005. Environmental quality and evolutionary potential: lessons from wildpopulations. Proc. R. Soc. B 272:141525

20. Cheviron ZA, Brumeld RT. 2012. Genomic insights into adaptation to high-altitude environments. Heredity 108:35461

21. Chown SL, Gaston KJ. 2010. Body size variation in insects: a macroecological perspective. Biol. Rev.

85:1396922. Clark MS, Thorne MAS, Vieira FA, Cardoso JCR, Power DM, Peck LS. 2010. Insights into shelldeposition in the Antarctic bivalve Laternula elliptica: gene discovery in the mantle transcriptome using454 pyrosequencing. BMC Genomics 11:362

23. ClowersKJ,LymanRF, MackayTFC,MorganTJ.2010.Geneticvariationin senescencemarkerprotein-30 is associated with natural variation in cold tolerance in Drosophila. Genet. Res. 92:10313

24. Colinet H, Lee SF, Hoffmann A. 2010. Knocking down expression of Hsp22 and Hsp23 by RNA interference affects recovery from chill coma in Drosophila melanogaster . J. Exp. Biol. 213:414650



20/28

25. Collinge JE, Anderson AR, Weeks AR, Johnson TK, McKechnie SW. 2008. Latitudinal and coldtolerancevariationassociatewithDNA repeat-numbervariation in the hsr-omegaRNA geneof Drosophilmelanogaster . Heredity 101:26070

26. Collins S, Bell G. 2004. Phenotypic consequences of 1,000 generations of selection at elevated CO2 ina green alga. Nature 431:56669

27. Conner JK, Hartl DL. 2004. A Primer of Ecological Genetics . Sunderland, MA: Sinauer Assoc.28. Cotton PA. 2003. Avian migration phenology and global climate change. Proc. Natl. Acad. Sci. US

100:1221922

29. Dawson TP, Jackson ST, House JI, Prentice IC, Mace GM. 2011. Beyond predictions: biodiversityconservation in a changing climate. Science 332:5358

30. Ekblom R, Galindo J. 2011. Applications of next generation sequencing in molecular ecology of nomodel organisms. Heredity 107:115

31. Etterson JR, Shaw RG. 2001. Constraint to adaptive evolution in response to global warming. Scienc294:15154

32. Fournier-Level A, Korte A, Cooper MD, Nordborg M, Schmitt J, Wilczek AM. 2011. A map of locadaptation in Arabidopsis thaliana. Science 333:8689

33. Franks SJ. 2011. Plasticity and evolution in drought avoidance and escape in the annual plant Brassicrapa. New Phytol. 190:24957

34. Franks SJ, Avise JC, Bradshaw WE, Conner JK, Etterson JR, et al. 2008. The Resurrection Initiativstoring ancestral genotypes to capture evolution in action. BioScience 58:87073

35. Franks SJ, Sim S, Weis AE. 2007. Rapid evolution of owering time by an annual plant in response tclimate uctuation. Proc. Natl. Acad. Sci. USA 104:127882

36. Franks SJ, Weis AE. 2008. A change in climate causes rapid evolution of multiple life-history traits atheir interactions in an annual plant. J. Evol. Biol. 21:132134

37. Gardner JL, Peters A, Kearney MR, Joseph L, Heinsohn R. 2011. Declining body size: a third universresponse to warming? Trends Ecol. Evol. 26:28591

38. Garroway CJ, Bowman J, Cascaden TJ, Holloway GL, Mahan CG, et al. 2010. Climate change inducehybridization in ying squirrels. Glob. Change Biol. 16:11321

39. Gibert JM, Peronnet F, Schlotterer C. 2007. Phenotypic plasticity in Drosophila pigmentation caused bytemperature sensitivity of a chromatin regulator network. PLoS Genet. 3:26680

40. Gienapp P, Teplitsky C, Alho JS, Mills JA, Merila J. 2008. Climate change and evolution: disentanglienvironmental and genetic responses. Mol. Ecol. 17:16778

41. Gonzalez J, Karasov TL, Messer PW, Petrov DA. 2010. Genome-wide patterns of adaptation to temperate environments associated with transposable elements in Drosophila. PLoS Genet. 6:e1000905

42. Grant PR, Grant BR. 2002. Unpredictable evolution in a 30-year study of Darwins nches. Scienc296:70711

43. Hancock AM,Brachi B, FaureN, HortonMW,Jarymowycz LB,et al.2011. Adaptation to climate acrossthe Arabidopsis thaliana genome. Science 333:8386

44. Hansen MM, Olivieri I, Waller DM, Nielsen EE, GeM Working Group. 2012. Monitoring adaptivegenetic responses to environmental change. Mol. Ecol. 21:131129

45. HauserMT, Aufsatz W, Jonak C, Luschnig C. 2011. Transgenerational epigenetic inheritance in plants.Biochim. Biophys. Acta Gene Regul. Mech. 1809:45968

46. Healy TM, Tymchuk WE, Osborne EJ, Schulte PM. 2010. Heat shock response of killish ( Fundulu

heteroclitus ): candidate gene and heterologous microarray approaches. Physiol. Genomics 41:1718447. Hendry AP, Day T. 2005. Population structure attributable to reproductive time: isolation by time andadaptation by time. Mol. Ecol. 14:90116

48. Hill JK,Grifths HM,Thomas CD.2011.Climate changeandevolutionary adaptations at species rangemargins. Annu. Rev. Entomol. 56:14359

49. Hoffmann AA, Sgr o CM. 2011. Climate change and evolutionary adaptation. Nature 470:4798550. Hoffmann AA, Sorensen JG, Loeschcke V. 2003. Adaptation of Drosophila to temperature extremes:

bringing together quantitative and molecular approaches. J. Therm. Biol. 28:175216

204 Franks Hoffmann


21/28

51. Hoffmann AA, Weeks AR. 2007. Climatic selection on genes and traits after a 100 year-old invasion: acritical look at the temperate-tropical clines in Drosophila melanogaster from eastern Australia. Genetica129:13347

52. Inouye DW. 2008. Effects of climate change on phenology, frost damage, and oral abundance of montane wildowers. Ecology 89:35362

53. Intergov. Panel Clim. Change (IPCC). 2007. Climate change 2007: the physical science basis. Contrib.Work. Group I Fourth Assess. Rep., Intergov. Panel Clim. Change, Cambridge, UK

54. Jablonka E, Raz G. 2009. Transgenerational epigenetic inheritance: prevalence, mechanisms, and im-

plications for the study of heredity and evolution. Q. Rev. Biol. 84:1317655. James AC, Partridge L. 1995. Thermal evolution of rate of larval development in Drosophila melanogaster in laboratory and eld populations. J. Evol. Biol. 8: 31530

56. Jenkins NL, Hoffmann AA. 1994. Genetic and maternal variation for heat resistance in Drosophila fromthe eld. Genetics 137:78389

57. Jensen LT, Cockerell FE, Kristensen TN, Rako L, Loeschcke V, et al. 2010. Adult heat tolerance variation in Drosophila melanogaster is not related to Hsp70 expression. J. Exp. Zool. Part A 313A:3544

58. Johnson TK, Carrington LB, Hallas RJ, McKechnie SW. 2009. Protein synthesis rates in Drosophilaassociate with levels of the hsr-omega nuclear transcript. Cell Stress Chaperones 14:56977

59. Johnson TK, Cockerell FE, McKechnie SW. 2011. Transcripts from the Drosophila heat-shock genehsr-omega inuence rates of protein synthesis but hardly affect resistance to heat knockdown. Mol. Genet.Genomics 285:31323

60. Kang HM, Zaitlen NA, Wade CM, Kirby A, Heckerman D, et al. 2008. Efcient control of populationstructure in model organism association mapping. Genetics 178:170961. Kantar M, Lucas SJ, Budaki H. 2011. Drought stress: molecular genetics and genomics approaches. In

Plant Responses to Drought and Salinity Stress: Developments in a Post-Genomic Era, ed. I Turkan, pp. 44593.London: Academic

62. Karell P, Ahola K, Karstinen T, Valkama J, Brommer JE. 2011. Climate change drives microevolutionin a wild bird. Nat. Commun. 2:208

63. Kellermann V, van Heerwaarden B, Sgr o CM, Hoffmann AA. 2009. Fundamental evolutionary limits inecological traits drive Drosophila species distributions. Science 325:124446

64. Kelly MW, Sanford E, Grosberg RK. 2012. Limited potential for adaptation to climate change in abroadly distributed marine crustacean. Proc. R. Soc. B 279:34956

65. Kennington WJ, Hoffmann AA, Partridge L. 2007. Mapping regions within cosmopolitan inversion

In(3R)Payne associated with natural variation in body size in Drosophila melanogaster . Genetics 177:5495666. Kolaczkowski B, Kern AD, Holloway AK, Begun DJ. 2011. Genomic differentiation between temperate

and tropical Australian populations of Drosophila melanogaster . Genetics 187:2456067. Kuparinen A, Savolainen O, Schurr FM. 2009. Increased mortality can promote evolutionary adaptation

of forest trees to climate change. For. Ecol. Manag. 259:1003868. Le CorreV, Kremer A. 2012. Thegenetic differentiationat quantitative trait loci under local adaptation.

Mol . Ecol . 21:15486669. Lee SF, Chen Y, Varan AK, Wee CW, Rako L, et al. 2011. Molecular basis of adaptive shift in body size

in Drosophila melanogaster : functional andsequence analyses of theDcagene. Mol. Biol. Evol.28:239340270. LempeJ, Balasubramanian S,SureshkumarS, SinghA,SchmidM, WeigelD. 2005.Diversityof owering

responses in wild Arabidopsis thaliana strains. PLoS Genet. 1:1091871. Lenoir J, Gegout JC, Marquet PA, de Ruffray P, Brisse H. 2008. A signicant upward shift in plant

species optimum elevation during the 20th century. Science 320:17687172. Levine MT, Eckert ML, Begun DJ. 2011. Whole-genome expression plasticity across tropical and

temperate Drosophila melanogaster populations from eastern Australia. Mol. Biol. Evol. 28:2495673. Li Y, Huang Y, Bergelson J, Nordborg M, Borevitz JO. 2010. Association mapping of local climate-

sensitive quantitative trait loci in Arabidopsis thaliana. Proc. Natl. Acad. Sci. USA 107:2119920474. LoeschckeV, Kristensen TN,NorryFM.2011.Consistent effects of a majorQTLfor thermal resistance

in eld-released Drosophila melanogaster . J. Insect Physiol. 57:12273175. Lynch M, Walsh B. 1998. Genetics and Analysis of Quantitative Traits . Sunderland, MA: Sinauer Assoc.



22/28

76. Malcom JW. 2011. Smaller gene networks permit longer persistence in fast-changing environments PLoS ONE 6:e14747

77. Mariac C, Jehin L, Saidou AA, Thuillet AC, Couderc M, et al. 2011. Genetic basis of pearl milladaptation alongan environmental gradientinvestigatedbya combination ofgenomescanandassociationmapping. Mol. Ecol. 20:8091

78. Matesanz S, Gianoli E, Valladares F. 2010. Global change and the evolution of phenotypic plasticiin plants. In Year in Evolutionary Biology, ed. CD Schlichting, TA Mousseau, pp. 3555. Malden, MA Wiley-Blackwell

79. McDonald JH, Kreitman M. 1991. Adaptive protein evolution at the Adh locus in Drosophila. Nature351:6525480. McKay JK, Richards JH, Mitchell-Olds T. 2003. Genetics of drought adaptation in Arabidopsis thalian

I. Pleiotropy contributes to genetic correlations among ecological traits. Mol. Ecol. 12:11375181. McKechnie SW, Blacket MJ, Song SV, Rako L, Carroll X, et al. 2010. A clinally varying promot

polymorphism associated with adaptive variation in wing size in Drosophila. Mol . Ecol . 19:775784.82. McMahon SM, Harrison SP, Armbruster WS, Bartlein PJ, Beale CM, et al. 2011. Improving assessmen

and modelling of climate change impacts on global terrestrial biodiversity. Trends Ecol. Evol. 26:2495983. McNamara JM, Barta Z, Klaassen M, Bauer S, 2011. Cues and the optimal timing of activities und

environmental changes. Ecol . Lett . 14:11839084. Michaels SD. 2009. Flowering time regulation produces much fruit. Curr. Opin. Plant Biol. 12:758085. Miller-Rushing AJ, Primack RB. 2008. Global warming and owering times in Thoreaus Concord:

community perspective. Ecology 89:3324186. Morgan TJ, Mackay TFC. 2006. Quantitative trait loci for thermotolerance phenotypes in Drosophil

melanogaster . Heredity 96:2324287. Moritz C, Patton J, Conroy C, Parra J, White G, Beissinger S. 2008. Impact of a century of climat

change on small-mammal communities in Yosemite National Park, USA. Science 322:2616488. Narum SR, Campbell NR, Kozfkay CC, Meyer KA. 2010. Adaptation of redband trout in desert an

montane environments. Mol. Ecol. 19:46223789. Neuwald JL, Valenzuela N. 2011. The lesser known challenge of climate change: thermal variance a

sex-reversal in vertebrates with temperature-dependent sex determination. PLoS ONE 6:e1811790. Norry FM, Larsen PF, Liu YJ, Loeschcke V. 2009. Combined expression patterns of QTL-linked

candidate genes best predict thermotolerance in Drosophila melanogaster . J. Insect Physiol. 55:10505791. NorryFM, ScannapiecoAC,SambucettiP,Bertoli CI,Loeschcke V.2008.QTLfor thethermotolerance

effect of heat hardening, knockdown resistance to heat and chill-coma recovery in an intercontinentaset of recombinant inbred lines of Drosophila melanogaster . Mol. Ecol. 17:457081

92. Nuzhdin SV,Brisson JA, Pickering A, Wayne ML,Harshman LG, McIntyre LM.2009. Natural genetic variation in transcriptome reects network structure inferred with major effect mutations: insulin/TORand associated phenotypes in Drosophila melanogaster . BMC Genomics 10:124

93. Orozco-Terwengel P,KapunM, NolteV, KoerR, FlattT, Schl ottererC.2012.Adaptation of Drosophilto a novel laboratory environment reveals temporally heterogeneous trajectories of selected alleles. Mol Ecol . In press, doi: 10.1111/j.1365-294X.2012.05673.x

94. Ostling P, Bjork JK, Roos-Mattjus P, Mezger V, Sistonen L. 2007. Heat shock factor 2 (HSF2) contributes to inducible expression of hsp genes through interplay with HSF1. J. Biol. Chem. 282:707786

95. Ozgul A, Tuljapurkar S, Benton TG, Pemberton JM, Clutton-Brock TH, Coulson T. 2009. The dy-namics of phenotypic change and the shrinking sheep of St. Kilda. Science 325:46467

96. Parkash R,SharmaV, KalraB.2008. Climatic adaptations ofbody melanisationinDrosophila melanogast

from western Himalayas. Fly 2:1111797. Parmesan C, Yohe G. 2003. A globally coherent ngerprint of climate change impacts across natur

systems. Nature 421:374298. Pelini SL, Keppel JA, Kelley AE, Hellmann JJ. 2010. Adaptation to host plants may prevent rapid ins

responses to climate change. Glob. Change Biol. 16:29232999. Pennisi E. 2011. Banking seeds for future evolutionary scientists. Science 333:1693

100. Phifer-Rixey M, Heckman M, Trussell GC, Schmidt PS. 2008. Maintenance of clinal variation for shecolour phenotype in the at periwinkle Littorina obtusata. J. Evol. Biol. 21:96678

206 Franks Hoffmann


23/28

101. Primack RB. 1985. Patterns of owering phenology in communities, populations, individuals and singleowers. In Population Structure of Vegetation, ed. J White, pp. 57193. Dordrecht, The Netherlands:Springer

102. Prunier J, Laroche J, Beaulieu J, Bosquet J. 2011. Scanning the genome for gene SNPs related to climateadaptation and estimating selection at the molecular level in boreal black spruce. Mol. Ecol. 20:170216

103. Pulido F, Berthold P. 2010. Current selection for lower migratory activity will drive the evolution of residency in a migratory bird population. Proc. Natl. Acad. Sci. USA 107:734146

104. Quinn NL,McGowanCR, Cooper GA,KoopBF, DavidsonWS.2011. Identication ofgenesassociated

with heat tolerance in Arctic charr exposed to acute thermal stress. Physiol. Genomics 43:68596105. Rako L, Anderson AR, Sgr o CM, Stocker AJ, Hoffmann AA. 2006. The association between inversion In(3R)Payne and clinally varying traits in Drosophila melanogaster . Genetica 128:37384

106. Rand DM, Weinreich DM, Lerman D, Folk D, Gilchrist GW. 2010. Three selections are better thanone: clinal variation of thermal QTL from independent selection experiments in Drosophila. Evolution64:292134

107. Reed TE, Schindler DE, Hague MJ, Patterson DA, Meir E, et al. 2011. Time to evolve? Potentialevolutionary responses of Fraser River sockeye salmon to climate change and effects on persistence. PLoS ONE 6:e20380

108. Reusch TBH, Wood TE. 2007. Molecular ecology of global change. Mol. Ecol. 16:397392109. Rezende EL, Balanya J, Rodriguez-Trelles F, Rego C, Fragata I, et al. 2010. Climate change and chro-

mosomal inversions in Drosophila subobscura. Clim. Res. 43:10314

110. Richards CL, Bossdorf O, Muth NZ, Gurevitch J, Pigliucci M. 2006. Jack of all trades, master of some?On the role of phenotypic plasticity in plant invasions. Ecol. Lett. 9:98193111. Rokas A, Abbot P. 2009. Harnessing genomics for evolutionary insights. Trends Ecol. Evol. 24:192200112. Samani P, Bell G. 2010. Adaptation of experimental yeast populations to stressful conditions in relation

to population size. J. Evol. Biol. 23:79196113. SarupP,SorensenJG,KristensenTN, HoffmannAA,Loeschcke V,etal.2011.Candidategenesdetected

in transcriptome studies are strongly dependent on genetic background. PLoS ONE 6:e15644114. Schlichting CD, Pigliucci M. 1998. Phenotypic Evolution: A Reaction Norm Perspective. Sunderland, MA:

Sinauer Assoc.115. Sgr o CM, Overgaard J, Kristensen TN, Mitchell KA, C

genetics of climate change adaptation

Documents