Keller Et Al. 2013 Plasticidad Altitudinal

REVIEW

Widespread phenotypic and genetic divergence along altitudinalgradients in animals

I . KELLER*†‡ , J . M. ALEXANDER*, R. HOLDEREGGER*§ & P. J . EDWARDS*

*Institute of Integrative Biology, ETH Zentrum CHN, ETH Z€urich, Universit€atsstrasse 16, Z€urich, Switzerland

†Department of Fish Ecology and Evolution, EAWAG Swiss Federal Institute of Aquatic Science and Technology, Center of Ecology, Evolution and Biochemistry,

Kastanienbaum, Switzerland

‡Department of Aquatic Ecology and Macroevolution, Institute of Ecology and Evolution, University of Bern, Bern, Switzerland

§WSL Swiss Federal Research Institute, Birmensdorf, Switzerland

Keywords:

adaptation;

common garden experiment;

elevation;

molecular adaptation;

outlier scan;

phenotypic divergence.

Abstract

Altitudinal gradients offer valuable study systems to investigate how adap-

tive genetic diversity is distributed within and between natural populations

and which factors promote or prevent adaptive differentiation. The environ-

mental clines along altitudinal gradients tend to be steep relative to the

dispersal distance of many organisms, providing an opportunity to study the

joint effects of divergent natural selection and gene flow. Temperature is

one variable showing consistent altitudinal changes, and altitudinal gradi-

ents can therefore provide spatial surrogates for some of the changes antici-

pated under climate change. Here, we investigate the extent and patterns of

adaptive divergence in animal populations along altitudinal gradients by sur-

veying the literature for (i) studies on phenotypic variation assessed under

common garden or reciprocal transplant designs and (ii) studies looking for

signatures of divergent selection at the molecular level. Phenotypic data

show that significant between-population differences are common and taxo-

nomically widespread, involving traits such as mass, wing size, tolerance to

thermal extremes and melanization. Several lines of evidence suggest that

some of the observed differences are adaptively relevant, but rigorous tests

of local adaptation or the link between specific phenotypes and fitness are

sorely lacking. Evidence for a role of altitudinal adaptation also exists for a

number of candidate genes, most prominently haemoglobin, and for anony-

mous molecular markers. Novel genomic approaches may provide valuable

tools for studying adaptive diversity, also in species that are not amenable to

experimentation.

Introduction

The geographical distribution of many species is so

broad that various characteristics of their environment

vary either abruptly or in a clinal manner within their

range. A common pattern observed in response to

such environmental heterogeneity is local adaptation,

where, at a given location, the fitness of local indi-

viduals is higher than that of immigrants from other

environments (Kawecki & Ebert, 2004). Local adapta-

tion is possible if populations contain ecologically rele-

vant genetic variation and if divergent selection

between different environments is strong relative to the

rate of gene flow (Morjan & Rieseberg, 2004). The dis-

tribution of adaptive genetic diversity and the factors

promoting or preventing adaptive divergence are of

fundamental interest to evolutionary ecologists but

remain poorly characterized in most natural popula-

tions (see Hereford, 2009a for recent review). It is also

largely unclear how consistently different species

respond to similar selection pressures. A better under-

standing of these issues has direct implications for

Correspondence: Irene Keller, Department of Clinical Research,

Murtenstrasse 35, 3010 Bern, Switzerland.

Tel.: +41 31 631 3018; fax: +41 31 631 4888;

e-mail: [email protected]

ª 2 01 3 THE AUTHORS . J . E VOL . B I OL .

1JOURNAL OF EVOLUT IONARY B IO LOGY ª 20 1 3 EUROPEAN SOC I E TY FOR EVOLUT IONARY B IO LOGY

doi: 10.1111/jeb.12255

conservation and management, for example, by

improving our ability to assess the future of populations

in rapidly changing environments or to anticipate the

effect of changes to population connectivity.

In addition to the environmental changes observed

in space, anthropogenic climate change is expected to

lead to temporal changes, but its implications for local

climatic conditions are likely to vary widely. Thermal

environments at high latitudes, for example, may

become more similar to the current thermal environ-

ments at lower latitudes. Other environmental vari-

ables, notably day length, are not expected to change,

which may lead to completely novel environmental

conditions. This suggests that range shifts (Parmesan &

Yohe, 2003; Parmesan, 2006) may be insufficient

for locally adapted populations to track their pre-

ferred (multidimensional) environment and additional

responses are necessary. Phenotypic plasticity provides

one mechanism to deal with environmental variability,

but plastic responses may be possible only within

certain limits, and evolutionary change may be neces-

sary in the face of large and consistent environmental

change (e.g. Gienapp et al., 2008). Indeed, a number of

case studies report evidence of such microevolutionary

changes in response to global warming in natural popu-

lations (reviewed in Bradshaw et al., 2006; Hoffmann &

Sgr�o, 2011).Spatial gradients can serve as surrogates for at least

some of the temporal changes anticipated under climate

change (Reusch & Wood, 2007), providing an opportu-

nity to investigate the historical and current responses

of natural populations to climate-related selection pres-

sures. Altitudinal gradients are particularly relevant in

this context because they are also climate gradients.

Some of the environmental changes along altitudinal

gradients are specific to certain locations or biogeo-

graphical regions, whereas others, namely decreasing

temperature, decreasing atmospheric pressure and

increasing intensity of solar radiation (K€orner, 2007),

are physical properties shared by altitudinal gradients

worldwide, allowing particular effects to be studied in

numerous replicated systems.

Altitudinal gradients offer a valuable contrast to lati-

tudinal gradients, especially with respect to geographi-

cal scale. Altitudinal gradients are typically steep, with

environmental transitions occurring at spatial scales

that are small relative to the dispersal distances of many

species. This has several important implications. First, it

means that the effects of divergent selection may often

be opposed by gene flow, which, if strong enough, acts

to homogenize allele frequencies between environ-

ments. Altitudinal gradients thus provide the opportu-

nity to investigate whether, and under which

conditions, adaptive divergence is possible in the face of

gene flow. Second, the small geographical scale of alti-

tudinal gradients also implies that confounding effects,

such as distinct regional evolutionary histories, are less

of an issue than in latitudinal surveys, which are often

performed across thousands of kilometres (e.g. Balany�aet al., 2006).

Many examples exist of phenotypic transitions associ-

ated with the changing environment along altitudinal

gradients. Plants often show conspicuous intraspecific

differences in growth form or leaf morphology between

high and low altitudes (K€orner, 2003), whereas pheno-

typic differences in animals can involve body size clines

(Chown & Klok, 2003) or, perhaps more conspicuously,

transitions from one generation per year at high alti-

tudes to two or more at lower altitudes (Hodkinson,

2005). What is often less clear, however, is whether

these phenotypic differences have a genetic basis or

result entirely from plastic responses to the

environment.

As a step towards a better understanding of the distri-

bution of adaptive genetic diversity along altitudinal

gradients, we surveyed the literature for studies on

genetic divergence in phenotypic traits and at func-

tional loci in animal populations. Our particular goal

was to identify general patterns emerging from these

studies by asking (i) whether some taxa are more prone

to differentiation than others, for example due to differ-

ences in specific species traits, (ii) whether adaptive

divergence is apparent at all geographical scales or

whether it tends to be rare between nearby populations

where gene flow may be high and (iii) whether differ-

ent species show similar responses to selection pressures

associated with altitude.

Literature survey

We performed a literature survey to identify studies

investigating genetic differentiation between animal

populations (both aquatic and terrestrial) along altitudi-

nal gradients. We used ISI Web of Knowledge to con-

duct a search for papers on (altitud* OR elevation*)AND (gradient OR transect OR cline) AND (genetic OR

‘common garden’ OR transplant) NOT plant to obtain a

list of ca. 500 publications. Based on the abstracts, we

retained two types of studies. The first consisted of

papers reporting measurements of phenotypic traits for

individuals from different altitudinal origins studied

under common garden conditions or in a reciprocal

transplant design. Data on phenotypic traits collected

directly in the field were included only in three cases

where additional information supported a genetic basis

for the trait (wing melanization, Ellers & Boggs, 2002,

2004a; macroptery, Fairbairn & King, 2009; and heat-

shock protein expression, Dahlhoff & Rank, 2000). The

second group contained papers providing molecular

evidence of adaptive genetic differences between popu-

lations at different altitudes. These studies typically

investigated associations between genotypes and alti-

tude or used outlier locus detection (e.g. Storz, 2005) to

identify loci showing unusually high between-popula-

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2 I . KELLER ET AL.

tion differentiation. The focus was on intraspecific phe-

notypic or genetic diversity. Papers on incipient species

pairs were included only if there was evidence of

on-going gene flow between the two species. Additional

studies were identified based on the bibliography in rel-

evant papers as well as from thematically related review

articles (Leinonen et al., 2008; Conover et al., 2009;

Hereford, 2009; Nosil et al., 2009).

Phenotypic data

Data availability and methodological limitationsA total of 68 publications met our selection criteria for

phenotypic data, and these contained data from 44 dif-

ferent species: 24 arthropods, 19 chordates and one

mollusc. From 66 of these papers (Table S1), we were

able to extract data for at least one phenotypic trait

from tables or from figures using g3data (http://www.

frantz.fi/software/g3data.php).

Among the arthropods, Diptera was the best-

represented order with 14 different species, followed

by Lepidoptera and Orthoptera with three species each.

Among the chordates, two-thirds of the species were

amphibians or reptiles. The maximum altitudinal dis-

tance between sampling locations ranged from 126 m

(Eales et al., 2010) to 4000 m (Le�on-Velarde et al.,

1996). Most studies were performed at a relatively

small scale with a median Euclidian distance of

135 km between the two most distant source popula-

tions (range: 5–3900 km, distances were estimated

using Google Maps if not provided in the original

publication).

The majority of papers reported data on phenotypic

traits recorded from individuals reared under the same

environmental conditions. Although such common gar-

den experiments are valuable to investigate the genetic

basis of traits (but see caveat below), the adaptive

significance of between-population differences cannot

be inferred. Such an assessment would require results

from reciprocal transplants or at least from multiple

common garden experiments, which try to mimic the

range of natural conditions associated with changes in

altitude. Such reciprocal transplant experiments have

been performed only for three species (the frog Rana

sylvatica, Berven, 1982a,b; the butterfly Colias philodice

eriphyle, Ellers & Boggs, 2004b; the lizard Psammodromus

algirus, Iraeta et al., 2006), in all cases in addition to

common garden experiments.

Further, to exclude effects of the native environment

on phenotypes, experimental animals should be reared

in a common environment for two or more generations

prior to measurement (Kawecki & Ebert, 2004). This

was the case in only about one-third of the studies, all

of them on flies. Another 13% of the studies used

wild-caught individuals (F0), whereas the majority used

laboratory-reared offspring of wild-caught animals (F1;

38%). In these cases, the phenotype may still be

affected by the native environment through maternal

effects (Kawecki & Ebert, 2004).

Analysis and graphical overviewsWe used the assembled data to investigate whether

populations from different altitudes show genetically

based differences in phenotypic traits, initially ignoring

the adaptive significance of these differences. Further,

we investigated whether the altitudinal trends observed

for a given trait were similar across species. This second

analysis was conducted for 14 trait categories measured

in at least five different species, where each trait cate-

gory included several related traits as indicated in Figs 1

and S1. Melanization was also included due to its

potential relevance for thermoregulation, even though

this trait was only studied in three species. To account

for differences in the range of trait values, all observa-

tions were standardized within trait and study to mean

0 and variance 1. These standardized trait values were

then regressed against the altitude of the source popu-

lation assuming a linear relationship. Regressions were

calculated separately for each trait, study, common gar-

den environment and other subgroups (e.g. sex, age

class or study year) if available. Figures 1 and S1 show

the regression slopes for different trait categories, and

Table 1 provides a summary of the main patterns.

Studies including only one high- and one low-

altitude source population, where regression slopes

were estimated based on only two data points, were dis-

tinguished from studies with multiple populations from

each elevation. Additionally, we retained information

about statistical significances as reported in the original

publications, distinguishing between significant effects

of altitude and of population. The latter category

included (i) studies using only two source populations,

in which case altitudinal and population effects could

not be distinguished (e.g. Conover et al., 2009), (ii)

reports that did not formally test for altitudinal effects

or (iii) studies where significant population differences

were not associated with altitude. We did not distin-

guish between significant main effects and significant

two-way interactions involving altitude or population.

This inclusion of significant interaction terms explains

why slope estimates near zero are sometimes displayed

as statistically significant in the figures.

Molecular dataThe second focus of our literature survey was on stud-

ies looking for signatures of divergent altitudinal selec-

tion at the molecular level. Many of these studies made

use of outlier locus detection (e.g. Storz, 2005) to deter-

mine whether between-population divergence at a

given gene or anonymous marker was significantly

higher than the genomic average. Additionally, we

included studies showing altitudinal clines in the

frequency of particular alleles at candidate genes or

anonymous regions of the genome. Similar to the


JOURNAL OF EVOLUT IONARY B IO LOGY ª 20 1 3 EUROPEAN SOC I E TY FOR EVOLUT IONARY B IO LOGY

Divergent altitudinal adaptation 3

(a)

(b)

(c)

(d)



4 I . KELLER ET AL.

Fig. 1 Observed changes in phenotypic traits in animals along altitudinal gradients. Shown are slopes from linear regression of trait value

against altitude of the source population, with trait values standardized to mean 0 and variance 1 within trait and study. Separate

estimates are shown for each data set, where data sets can be different common garden environments, latitudes, age classes, sexes, etc.

Each row represents a different species and summarizes data from one or several studies, as indicated in the ‘ref’ column. Several related

traits were combined into each trait category as specified in the ‘traits’ column. Shading indicates if the original publication reported

statistically significant effects of altitude (blue) or population (orange), a nonsignificant (n.s.) effect (red) or did not provide test results

(empty circle). Note that we did not distinguish between main effects and interactions involving altitude or population. The inclusion of

significant interaction terms explains why some slope estimates near zero are displayed as statistically significant. The size of the circles

indicates the number of source populations available to estimate the slopes (small: 2 sources; large: > 2 sources). Asterisks indicate traits for

which the sign of the slope was reversed to produce consistent patterns across traits. For the wing size traits, for instance, wing loading is

the only trait where a smaller trait value would indicate a larger wing. Consequently, if unadjusted, an increase in wing size with altitude

would result in a negative slope for wing loading but a positive slope for all remaining traits.

(a) Traits: a, wing/thorax ratio; b, wing loading*; c, wing length; d, wing width; e, wing centroid size; f, wing area. Ref: 1 = Bears et al.

(2008), 2 = Bubliy & Loeschke (2004), 3 = Dahlgaard et al. (2001), 4 = Norry et al. (2001), 5 = Sambucetti et al. (2006), 6 = Collinge et al.

(2006) 7 = Pitchers et al. (2012), 8 = Stalker & Carson (1948), 9 = Tantowijoyo & Hoffmann (2011), 10 = Belen et al. (2004), 11 = Karan

et al. (2000), 12 = Karl et al. (2008). *Sign of slope reversed.

(b) Traits: a, chill coma recovery time*; b, cold shock survival; c, lower limiting T for embryonic development*. Ref: 1 = Beattie (1987),

2 = Bridle et al. (2009), 3 = Sarup et al. (2009), 4 = Sorensen et al. (2005), 5 = Collinge et al. (2006), 6 = Parkash et al. (2010), 7 = Karl

et al. (2008). *Sign of slope reversed.

(c) Traits: a, tadpole; b, at metamorphosis; c, pupa; d, at hatching; e, adult. Ref: 1 = Ficetola & De Bernardi (2005), 2 = Jasienski (2009),

3 = Sommer & Pearman (2003), 4 = Buckley et al. (2010), 5 = Bears et al. (2008), 6 = Stillwell & Fox (2009), 7 = Karan et al. (2000),

8 = Karl et al. (2008).

(d) Traits: a, embryonic development time (dt); b, larval dt; c, postdiapause dt; d, pupal dt; e, egg-adult; f, hatching-adult. Ref: 1 = Beattie

(1987), 2 = Jasienski (2009), 3 = Marquis & Miaud (2008), 4 = Tsuchiya et al. (2012), 5 = Bubliy & Loeschcke (2004), 6 = Folguera et al.

(2008), 7 = Norry et al. (2001), 8 = Sambucetti et al. (2006), 9 = Collinge et al. (2006), 10 = Etges (1989), 11 = Belen & Alten (2006),

12 = Blanckenhorn (1997), 13 = Karl et al. (2008), 14 = Tanaka & Brookes (1983), 15 = Dingle et al. (1990), 16 = Berner et al. (2004).

Table 1 Number of animal species showing significant phenotypic differences between altitudinal populations reared in a common

environment for different traits. Patterns are summarized based on the detailed figures. (A) An increase in trait value with altitude is

supported by all statistically significant tests based on > 2 populations (i.e. all large blue circles > 0 and no large orange circles). (B) A

decrease in trait value with altitude is supported by all statistically significant tests based on > 2 populations (i.e. all large blue circles < 0

and no large orange circles). (C) Statistically significant differences between populations are not or not consistently associated with altitude.

This category includes only species in which altitudinal effects were formally tested. In particular, estimates based only on two populations

(small circles) are not considered. In parentheses, we indicate the number of studies relying on animals reared in a common environment

for two or more generations before the experiments. Traits are listed in the order in which they appear in the text.

Trait category

Putative agent(s)

of selection

Expected

altitudinal

pattern

Number of species showing

# species

# different

taxonomic

groups* Details

(A) Consistent

increase

(B) Consistent

decrease

(C) Pop differences

not associated

with alt

Wing size Air density Increase 3 (3) 0 2 (2) 9 3 Fig. 1a

Heat tolerance T Decrease 0 2 (1) 2 (2) 5 3 Fig. S1a

Cold tolerance T Increase 3 (2) 0 2 (2) 6 3 Fig. 1b

HSP expression T, other stressors Unclear† 0 2 (0) 3 (2) 5 4 Fig. S1b

Desiccation

tolerance

Water availability Variable‡ 0 0 2 (2) 5 1 Fig. S1c

Mass T, resource availability Increase (?) 3 (1) 0 1 (1) 7 6 Fig. 1c

Body length T, resource availability Increase (?) 0 2 (0) 0 7 4 Fig. S1d

Development time T, season length Decrease (?) 0 3 (0) 3 (2) 13 5 Fig. 1d

Growth rate T, season length Increase (?) 0 0 1 (0) 6 3 Fig. S1e

Longevity Decrease (?) 0 1 (0) 3 (2) 6 2 Fig. S1f

Viability Unclear 0 0 2 (2) 11 3 Fig. S1g

Fecundity Unclear§ 1 (1) 1 (1) 3 (3) 11 4 Fig. S1h

HSP, heat-shock protein; T, temperature.

*Number of different orders (for Arthropoda) or classes (for Chordata, Mollusca).

†HSP expression is a very complex and general response to cellular stress, and predictions are difficult. The observed response may depend

heavily on common garden conditions (e.g. if these are closer to high- or low-altitude conditions).

‡Water availability often changes with altitude, but the direction of the change may vary among regions.

§If mortality risks increase with altitude due to increased environmental stochasticity, this could select for higher fecundity early in life.

However, the data set contains only two estimates of fecundity early in life and no trends can be inferred.




genome scan approaches, these patterns should ideally

be compared to those at putatively neutral genetic

markers to exclude the possibility that clines result

from purely neutral processes (e.g. isolation by dis-

tance; Storz, 2002). Such data from neutral loci were,

however, not always available (see comments in

Table 2).

We identified 30 studies that present evidence of

divergent selection under the criteria outlined above

(Table S1). These studies investigate 22 different spe-

cies, and the taxonomic focus was less biased towards

particular groups (i.e. Diptera) than in the phenotypic

data set.

Genetically based phenotypic variation alongaltitudinal gradients

In many studies, phenotypic traits measured in com-

mon garden environments varied significantly between

populations from different altitudinal origins. Among

the statistical tests performed in the original publica-

tions, 73% detected significant differences between

source populations or altitudes (including main and

interaction effects; Fig. 2). A very similar proportion of

significant test results was observed when we consid-

ered only studies using experimental animals bred in a

common environment for at least two generations

(70%; based on 142 tests from 27 studies).

We then asked whether traits measured in multiple

species tended to show the same changes along altitudi-

nal gradients. For the trait categories measured in five

or more species, clear predictions of the variation with

altitude could be formulated for three (Table 1),

whereas for several additional trait categories, the

expected patterns were more difficult to predict

(Table 1). In the following discussion, we particularly

focus on species showing statistically significant associa-

tions with altitude for particular traits (as reported in

the original study), especially if these are consistent

across data subsets or studies (columns A and B in

Table 1). We additionally report all species for which

significant between-population differences in a given

trait were detected, but for which trait values did not

change linearly with altitude (column C in Table 1).

This latter category includes only species for which alti-

tudinal effects were formally tested. The results from

additional studies in which the experimental design

precluded testing altitudinal effects or where such

effects were either not tested or not significant are

shown in Figs 1 and S1 but not considered in Table 1

and the following discussion.

First, air density decreases with altitude, and in addi-

tion to its significance for respiration, this also implies

that more power is needed for flight. A possible adap-

tive response includes an increase in wing size relative

to body size (e.g. Dillon et al., 2006). In our data set,

traits related to wing size were investigated in seven fly

species, a butterfly and a bird (Fig. 1a), but only for

two traits – wing to thorax ratio (a in Fig. 1a) and wing

loading (b in Fig. 1a) – relative to body size. In all three

studies reporting significant altitudinal effects, wing size

increased consistently with altitude (Fig. 1a; Table 1).

Air temperature is a second environmental variable

that shows consistent altitudinal clines, dropping an

average 5.5°C per 1000 m (e.g. K€orner, 2007). Not sur-prisingly, traits potentially relevant to thermal adapta-

tion were well represented in our data set, including

diverse morphological, physiological, developmental

and behavioural traits. The most obvious prediction is

that the average cold tolerance of individuals should

increase with altitude, whereas heat tolerance should

decrease (Table 1). For heat tolerance, some significant

between-population differences were reported in all

five species (Fig. S1a), but only in two cases were these

differences related to altitude. In both, heat tolerance

decreased with altitude as predicted. Cold tolerance was

investigated in four Drosophila species, one frog and one

butterfly (Fig. 1b). In three of these species, an increase

in cold tolerance was observed in populations from

higher altitudes, while in a further two significant pop-

ulation differences were reported that were not associ-

ated with altitude (Table 1). Interestingly, the latter

studies were all conducted with populations from equa-

torial regions (< 30° north/south), whereas all studies

with higher latitude populations did find a positive cor-

relation of cold tolerance with altitude. Heat-shock pro-

teins (Fig. S1b), which are involved in general

responses to cellular stress (Morris et al., 2013), showed

either decreasing expression levels with altitude (two

species) or between-population differences that were

not consistently associated with altitude (three species;

Table 1).

Clinal change with altitude is also predicted for body

melanization, a morphological trait that probably has

thermoregulatory relevance, as darker bodies absorb

more energy (Clusella Trullas et al., 2007). Body melan-

ization along altitudinal gradients was studied in only

three species, with the expected positive correlation

with altitude being found in each case (butterfly Colias

philodice eriphyle, Ellers & Boggs, 2002, 2004a; Drosophila

melanogaster, Sub-Saharan Africa: Pool & Aquadro,

2007; India: Parkash et al., 2008, 2010; Drosophila ameri-

cana, Wittkopp et al., 2011). In addition to the thermo-

regulatory advantages, darker individuals could be

better protected against elevated UV radiation at higher

altitudes, and in some Drosophila populations, body pig-

mentation also shows a strong positive correlation with

desiccation tolerance (Parkash et al., 2008; but not

Wittkopp et al., 2011; see Fig. S1c for results on desicca-

tion tolerance).

The altitudinal patterns expected for traits related to

body size are less clear (Table 1). According to Berg-

mann’s rule (e.g. Gardner et al., 2011), endotherms

tend to be larger in cooler environments due to the



6 I . KELLER ET AL.

Table

2Candidate

loci

andanonymousmarkers

(outlierloci)showingevidence

ofadaptivedifferentiationalongaltitudinalgradients

inanim

als.

Species

Common

name

Gene/M

arker

Gene

functio

n

Potential

selective

agent

Evidenceof

adaptivesignificance

Comments

Reference

Elevated

Fst

Altitudinal

cline

Candidate

genes A

nascanoptera

Cinnamonteal

Hemoglobin

aA,bA

subunit

O2transp

ort

O2partialpressure

•ElevatedFst

onlyforbA

Wilsonetal.(2013)

Anasflavirostris

Speckledteal

Hemoglobin

aA,bA

subunit

O2transp

ort

O2partialpressure

•McCracke

netal.(2009)

Anasgeorgica

Yellow-billedpintail

Hemoglobin

aA,bA

subunit

O2transp

ort

O2partialpressure

•ElevatedFst

onlyforbA

McCracke

netal.(2009)

Lophonettasp

ecularioides

Crestedduck

Hemoglobin

aD,aA

,bAsu

bunits

O2transp

ort

O2partialpressure

•Bulgarella

etal.(2012)

Zonotrichia

capensis

Rufous-collaredsp

arrow

ND3

NADH

dehyd

rogenase

subunit3(m

itochondria

l)

Enyzmein

oxidative

phosp

horylatio

n

(OXPHOS)pathway

Possibly

temperature

•Cheviron&Brumfield

(2009)

Crocidura

russula

White-toothedsh

rew

Controlregion

Secondhyp

ervaria

ble

domain

(HVII)

ofthe

mito

chondria

lcontrol

region

Non-coding

Possibly

temperature

•Non-shiverin

g

therm

ogenesisis

influencedbyinteractio

n

betw

eenhaplotypeandsex

Ehingeretal.(2002),

Fontanillasetal.(2005)

Homosapiens

Human(Tibetans&

Andeans)

EGLN1

eglninehomolog1

Enzymein

the

hyp

oxia-inducible

factor(HIF)pathway

O2partialpressure

•Putativehigh-altitude

allelesreducehemoglobin

concentratio

n.High

altitudevaria

nts

differ

betw

eenTibetans

andAndeans

Bigham

etal.(2010),

Sim

onso

netal.(2010),

Pengetal.(2011)

Homosapiens

Human(Tibetans)

EPAS1

EndothelialPASdomain-

containingprotein

1(=

Hyp

oxia-inducible

factor-

2a[HIF-2a])

Transcrip

tionfactor

invo

lvedin

the

inductio

nofgenes

regulatedbyoxygen

O2partialpressure

•With

inTibetans,

EPAS1

allelesare

correlated

with

erythrocytecountand

hemoglobin

concentratio

n

Yietal.(2010),Bigham

etal.(2010),Peng

etal.(2011)

Homosapiens

Human(Andeans)

NOS2A

Nitric

oxidesynthase

2A

Enzymein

the

hyp

oxia-inducible

factor(HIF)pathway;

invo

lvedin

nitric

oxide

(NO)synthesis,

which

plays

arole

invaso

dilatio

n

andincreasedbloodflow

O2partialpressure

•Bigham

etal.(2010)

Homosapiens

Human(Tibetans)

PPARA

Peroxiso

meproliferator-

activatedreceptoralpha

Enzymein

the

hyp

oxia-inducible

factor(HIF)pathway

O2partialpressure

•Putativehigh-altitude

allelesreducehemoglobin

concentratio

n.Outlier

statusofPPARAwas

notconfirmedin

Peng

etal.(2011)

Bigham

etal.(2010),

Sim

onso

netal.(2010),

Pengetal.(2011)

Homosapiens

Human(Andeans)

PRKAA1

Protein

kinase,AMP-

activated,alpha1

catalytic

subunit

Enzymein

thehyp

oxia-

inducible

factor(HIF)

pathway;

regulatio

n

ofcellularATP

O2partialpressure

•Bigham

etal.(2010)

Peromyscusmaniculatus

Deermouse

Albumin

Maintenanceof

biochemicalequilibria

inbodyfluids

Unclear,possibly

O2

partialpressure

•Storz

&Dubach(2004)

Peromyscusmaniculatus

Deermouse

Hemoglobin

a-globin

(HBA-T1,HBA-T2)

andb-globin

(HBB-T1,

HBB-T2)

O2transp

ort

O2partialpressure

•Storz

etal.(2009)




Table

2(Continued)

Species

Common

name

Gene/M

arker

Gene

functio

n

Potential

selective

agent

Evidenceof

adaptivesignificance

Comments

Reference

Elevated

Fst

Altitudinal

cline

Salm

otruttasp

p.

Europeantrout

UBA

Microsatellite

with

in3′

untranslatedtailofmajor

histocompatib

ility

complex

(MHC)regionIA

Immunedefense

Parasite

community

••

Kelleretal.(2011)

Agabusbipustulatus

Waterbeetle

a-Gpdh

a-Glycerophosp

hate

dehyd

rogenase

Energymetabolism

inflightmuscle

Unclear

•Sizeofwingandflight

muscle

decreaseswith

altitude

Drotz

etal.(2001,2012)

Sepsiscynipsea

Dungfly

MDH

Malate

dehyd

rogenase

Enzymein

citric

acid

cycle

Unclear,possibly

temperature

•Kraush

aaretal.(2002)

Droso

phila

melanogaster

Fruitfly

4candidate

genes

onchromoso

me2

invected,masterm

ind,

cric

klet,CG14591

Metabolism,

neurogenesis

Unclear,possibly

temperature

Varia

tionatthese

genes

underliesaltitudinalclinein

larvaldevelopmentaltim

e

Menschetal.(2010)

D.melanogaster

Fruitfly

ebony

Severalfunctio

nsin

biogenic

aminesynthesis

pathway

Possiblyclim

ate

Substitu

tionsin

the

enhanceroftheebony

locusare

associatedwith

abdominalmelanisatio

n

Rebeizetal.(2009)

Lycaenatityrus

Copperbutterfly

PGI

Phosp

hoglucose

isomerase

Glycolytic

enzyme

Possiblytemperature

•Individuals

from

low

sites

with

high-altitude-likePGI

genotyperesemble

high-

altitudeindividuals

with

resp

ectto

development

ratesandchill-coma

recovery

time

Karletal.(2008,2009)

Anonym

ousloci

Inversions

Droso

phila

buzzatti

Fruitfly

Chromoso

me2

Unkn

own

Possiblyclim

ate

•Rodrig

uezetal.(2000)

D.persim

ilis

Fruitfly

Chromoso

me3

Unkn

own

Possiblyclim

ate

•Noneutralreferenceloci

Dobzhansky

(1948)

D.pseudoobscura

Fruitfly

Chromoso

me3

Unkn

own

Possiblyclim

ate

•Dobzhansky

(1948),

Schaefferetal.(2003)

D.su

bobscura

Fruitfly

Allchromoso

mes

Unkn

own

Possiblyclim

ate

•Noneutralreferenceloci

Burla

etal.(1986)

D.robusta

Fruitfly

Chromoso

mes2,3,X

Unkn

own

Possiblyclim

ate

•Karyotypic

differences

underlievaria

tionin

severallifehistory

traits

Stalker&Carson(1948),

Levitan(1978),Etges

(1989)

Anophelesfunestus

Mosq

uito

es

Chromoso

mes2,3

Unkn

own

Possiblyclim

ate

•Ayala

etal.(2011)

AFLPandmicrosatellite

loci

Ranatemporaria

Commonfrog

8AFLPloci(2.0%)*

Unkn

own

Unkn

own

•Bonin

etal.(2006)

Microtusarvalis

Voles

12AFLPloci(0.8%)

Unkn

own

Unkn

own

•Fischeretal.(2011)

Rattusrattus

Rat

22AFLPloci(8.8%)

Unkn

own

Unkn

own,possibly

plaguepresence

•Plagueis

presentonly

athigheraltitudes

Tollenaere

etal.(2011)

Salm

otruttasp

p.

Europeantrout

5AFLPloci(2.2%)

Unkn

own

Unkn

own

•Kelleretal.(2012)

Droso

phila

buzzatii

Fruitfly

1Microsatellite

Unkn

own

Unkn

own

••

Barkeretal.(2011)

Droso

phila

melanogaster

Fruitfly

1Microsatellite

Unkn

own

Unkn

own

•Collingeetal.(2006)

*PGI,phosphoglucose

isomerase.

*ForAFLP-basedstudies,thepercentageofoutliers

amongallpolymorphic

loci

isgivenin

parentheses.



8 I . KELLER ET AL.

thermoregulatory advantages arising from a smaller

surface to volume ratio. Some ectotherms also comply

with Bergmann’s rule, although the underlying mecha-

nisms are likely to be different (Gardner et al., 2011);

furthermore, the opposite pattern is also common

(Blanckenhorn & Demont, 2004). Our data set, which

contained information for seven ectotherms from differ-

ent taxonomic groups, showed that in three species,

body mass tended to increase with altitude (Fig. 1c).

Body length changed in the opposite direction, with a

significant decrease with altitude reported from two

insects (Fig. S1d; Table 1).

In temperate regions, the period available for growth

shortens with increasing altitude (K€orner, 2007). At thesame time, the completion of different developmental

stages may take longer, especially in ectotherms,

because lower ambient temperatures slow down physi-

ological processes. An expected adaptation to these

conditions involves a compensatory response, with

high-altitude individuals developing or growing faster

than low-altitude individuals under a given thermal

regime (i.e. countergradient variation; e.g. Hodkinson,

2005). Such a pattern was indeed observed in all three

species for which development time was found to be

significantly associated with altitude (Fig. 1d; Table 1),

although the same number of between-population

differences was found that were unassociated with

altitude. Similarly, none of the observed between-popu-

lation differences in growth rate were associated with

altitude (Fig. S1e; Table 1).

Viability, longevity and fecundity were additional

life-history traits, which were repeatedly investigated,

almost exclusively in flies. A possible expectation here

could be that more variable and unpredictable high-

altitude environments favour a faster pace of life, char-

acterized by high investments in reproduction early in

life (Tieleman, 2009) and, perhaps, reduced longevity

(Table 1). Fecundity early in life has been estimated in

only two species (indicated by asterisks in Fig. S1h). All

three traits showed some significant between-popula-

tion differences, although demonstrations of altitudinal

patterns were rare (Fig. S1f–h; Table 1). Remarkably,

all four studies using multiple rearing temperatures

found that the decrease in longevity with altitude was

strongest in the coldest environment, that is, the condi-

tions most strongly resembling high-altitude conditions.

Overall, our literature survey provided clear evidence

for significant, genetically based phenotypic differences

Fig. 2 Number of significant (dark grey) and nonsignificant (light grey) results as reported in the original publications for different

geographical scales in animal species. The results from studies performed at a scale of less than 100 km are plotted again at a higher

resolution in the small inset and show that significant phenotypic differences between populations can be observed even at very local

scales. The numbers above the bars indicate the number of independent studies contributing to each distance class. Significant effects

include main effects or interactions involving population or altitude.




between populations of different altitudinal origin.

Comparisons across species identified several traits for

which parallel clinal patterns were observed in two or

three species, and for which the phenotypic changes

consistently occurred in the predicted direction (melan-

ization, wing size, cold and heat tolerance, mass, devel-

opment time; A or B in Table 1). However, in all of

these cases, several species also showed significant

between-population differences that were not, or at

least not consistently, associated with altitude (C in

Table 1). Overall, the available data are clearly limited.

The number of species for which data on a given trait

category were available was typically small (≤ 13) and

skewed towards particular taxonomic groups; further-

more, for several species, only two source populations

had been studied, making it impossible to distinguish

population effects from altitudinal effects.

Evidence of adaptive genetic divergence frommolecular studies

Almost all vertebrates rely on haemoglobin (Hb) for the

transport of oxygen. Hb is therefore an obvious candi-

date gene for adaptation to the changing O2 partial

pressure along altitudinal gradients, and the genes cod-

ing for different Hb subunits have been studied in a

number of species, most prominently birds (Table 2).

All of these studies found evidence of divergent selec-

tion for at least some of these genes. In deer mice, Storz

et al. (2009) further demonstrated that the b-globinvariant common in high-altitude populations has

indeed a higher O2 affinity.

Additional genes with a potential role for adaptation

to low O2 partial pressure have been detected in

humans through genome scans (Table 2). For example,

one enzyme from the hypoxia-inducible factor pathway

(EGLN1) has been identified as a potential target of

selection in both Tibetans and Andeans, but the haplo-

types common at high altitudes differ between the two

regions. Other genes have been implicated in high-alti-

tude adaptation in only one of the two populations

(Table 2).

Evidence of divergent selection along altitudinal gra-

dients is also available for other candidate genes,

including mitochondrial loci and several allozymes. For

many of these loci, a role in adapting to thermal condi-

tions is very plausible (Table 2), and in some cases, a

direct link between genotype and phenotype of

relevance for altitudinal adaptation has been demon-

strated. For example, Fontanillas et al. (2005) found

that nonshivering thermogenesis (i.e. mitochondrial

heat production in brown fat cells) in white-toothed

shrews was influenced by an interaction between sex

and mitochondrial haplotype. Copper butterflies from

low-altitude sites but with high-altitude-like genotypes

at an allozyme locus (phosphoglucose isomerase)

resembled high-altitude individuals with respect to

development rates and chill-coma recovery time (Karl

et al., 2008). And finally, in D. melanogaster, four candi-

date genes on chromosome 2 underlie altitudinal clines

in developmental time (Mensch et al., 2010), and muta-

tions in the cis regulatory elements of the ebony locus

underlie altitudinal pigmentation clines (Rebeiz et al.,

2009).

Chromosomal inversion polymorphisms have also

been repeatedly found to show altitudinal clines in

flies, where the presence of large polytene chromo-

somes has made chromosomal rearrangements more

amenable to study (Table 2). Several lines of evidence

suggest that climatic variables may play an important

role in maintaining spatial patterns in the frequency of

particular inversion genotypes. For instance, inversion

polymorphisms in Drosophila subobscura show similar

latitudinal clines on three continents (Balany�a et al.,

2006). The position of the clines has shifted in recent

decades, probably due to rising global temperatures

(Balany�a et al., 2006), and similar temporal changes

have been observed for a D. melanogaster inversion

polymorphism in Australia (Umina et al., 2005). Some

inversion polymorphisms also show consistent clines

with altitude and latitude (Etges et al., 2006 and refer-

ences therein) or recurrent seasonal fluctuations (Dobz-

hansky, 1943). Finally, several studies have

demonstrated a link between particular inversion poly-

morphisms and resistance to extreme temperatures

(reviewed in Hoffmann et al., 2004).

Six studies have also screened panels of anonymous

markers (e.g. AFLPs, microsatellite loci; Table 2) and

identified loci showing patterns consistent with diver-

gent selection along altitudinal transects (i.e. elevated

differentiation and/or genotype-altitude associations).

In the four AFLP-based studies, between 0.8% and

8.8% of all polymorphic loci showed evidence of adap-

tive differentiation (Table 2). It should be noted, how-

ever, that these studies used varying approaches for

identifying outliers. Furthermore, rather than being the

actual targets of selection, the anonymous markers

detected using these approaches are more likely to be

in linkage disequilibrium with unknown divergently

selected loci.

Synthesis

Pervasive evidence for genetically based phenotypicdifferentiationOur survey of the literature provides evidence for

genetically based phenotypic divergence along altitudi-

nal gradients for a wide range of species and traits,

including wing size, cold tolerance, mass and develop-

ment time (Fig. 1). This finding suggests that pheno-

typic divergence between populations is not rare, even

if its prevalence may be overestimated in our data set

due to a possible bias towards publishing significant

results. Our analyses also show that genetically based



10 I . KELLER ET AL.

phenotypic differentiation is taxonomically widespread,

with some significant differences between populations

being detected in all the groups studied.

Furthermore, in some cases, significant phenotypic

divergence occurred at local geographical scales (Fig. 2).

For example, eight studies detected significant diver-

gence between populations separated by ten kilometres

or less (Fig. 2, inset), which in several cases was well

within the dispersal range of the species. In Anolis

lizards, the morphological divergence was larger than

neutral genetic divergence (FST < QST; Eales et al.,

2010) and, similarly, Sarup et al. (2009) detected signif-

icant phenotypic divergence between Drosophila buzzatii

and D. simulans populations that were undifferentiated

at neutral molecular markers.

Are the observed differences adaptively relevant?The finding that phenotypic differentiation can be

maintained – at least sometimes – in the face of gene

flow strongly suggests that some between-population

differences are maintained by strong divergent natural

selection. And this conclusion is supported by addi-

tional lines of evidence from both the phenotypic and

molecular data sets. First, several phenotypic traits

showed consistent clines in multiple species in the

direction predicted from known environmental gradi-

ents, and secondly, many of the molecular studies iden-

tify loci showing signatures of divergent selection

(Table 2).

We can also predict that the level of genetic differen-

tiation at loci with a putative role in altitudinal adapta-

tion should increase with the altitudinal distance

between sites, assuming that the latter provides a rough

proxy for the intensity of divergent selection. Neutral

loci, on the other hand, should not show such an

association unless gene flow between different altitudi-

nal environments is reduced across the entire genome,

for example due to dispersal barriers or immigrant invi-

ability becoming stronger as the altitudinal contrast

increases. Consistent with these predictions, we found

that FST increased with maximum altitudinal distance

at candidate loci, but not at neutral loci (Fig. 3). How-

ever, these analyses were based on a subset of only 15

studies, and the data set did not lend itself to statistical

analysis. First, altitudinal distance in these data was

highly correlated with geographical distance (Pearson

correlation coefficient 0.77), making it impossible to

distinguish between the effects of the two variables.

Secondly, the representation of different taxonomic

groups was very uneven across altitudinal distance clas-

ses (e.g. all studies at > 4000 m are from birds). Despite

these limitations, it will be interesting for future studies

to investigate whether genetic differentiation increases

with altitudinal distance, and whether this increase is

genome-wide or limited to genomic regions with a

direct role in altitudinal adaptation.

Most of the phenotypic traits discussed above were

specifically selected by researchers because their adap-

tive relevance seemed likely and, for some of the traits,

clear expectations as to how they should respond to the

environmental change associated with altitude could be

formulated. As discussed above, a number of traits

showed patterns consistent with these predictions

(Table 1). However, in all cases, some species did not

conform to our expectations, for example showing no

significant between-population differences or differ-

ences that were unassociated with altitude. There are

many possible explanations for these conflicting results.

First, a given phenotypic trait may simply not be rele-

vant for fitness in populations that are diverging due to

random drift. Alternatively, if trait differences are

adaptively relevant, the link between a phenotypic trait

1000 2000 3000 4000

0.0

0.2

0.4

0.6

0.8

1.0

Max. altitudinal distance (m)

Fst

1000 2000 3000 4000

–0.4

–0.2

0.0

0.2

0.4

Max. altitudinal distance (m)

Res

idua

ls F

st ~

Geo

dis

tanc

e

Fig. 3 Left panel: Genetic differentiation between animal populations (FST) increases with the maximum altitudinal distance between

sampling sites at candidate loci (black diamonds), but not at neutral loci (grey squares). Each point represents a study, and in the majority

of cases (12 of 15 studies), the type of molecular marker was the same for candidate and neutral loci. Note that we did not assess the

statistical significance of the observed patterns because of limitations of the data set. First, different taxonomic groups were unevenly

represented in the different altitudinal distance classes. Secondly, altitudinal distance was highly correlated with geographical distance

making it impossible to disentangle the effects of the two variables: there was no longer an association between altitudinal distance and FSTafter removing the effect of geographical distance (right panel: residuals from a linear regression of FST against geographical distance,

plotted against altitudinal distance).




and fitness in a given altitudinal environment may

have been misjudged; for example, the optimal pheno-

type may be different from what we expect. Also, selec-

tion pressures may not change consistently along an

altitudinal gradient. For instance, small-scale topo-

graphical features influence ambient temperatures and

can produce local patterns that oppose large-scale gradi-

ents (Scherrer & K€orner, 2011). Finally, the trait mean

in a population can deviate from the local optimum

due to, for example, indirect selection resulting from

genetic correlations with other traits, lack of additive

genetic variation or immigration from other

environments (Lenormand, 2002; Hoffmann & Willi,

2008).

Open questions and directions for future research

Are phenotypic differences between populationsadaptively relevant and how does mean populationfitness change along altitudinal gradients?Although the available studies provide some evidence

of adaptive differences between populations, explicit

tests of local adaptation along altitudinal gradients, and

the ecological relevance of the observed interpopula-

tion differences, are clearly needed. Reciprocal trans-

plant experiments along altitudinal gradients would be

particularly valuable in this context, although we are

aware of only three animal species for which such

studies have been performed. All of these found that

some trait differences persisted also in common natural

environments (body size of frogs: Berven, 1982a; age

and size at first reproduction in frogs: Berven, 1982b;

flight activity of butterflies: Ellers & Boggs, 2004b; size

and growth rate in lizards: Iraeta et al., 2006), but none

actually demonstrated that fitness (or any fitness

proxy) was indeed higher for local than nonlocal

individuals.

More thorough studies of local adaptation will also

provide insights into how the relative and absolute fit-

ness of populations change along altitudinal gradients,

which is largely unknown. If most populations are

indeed adapted to their local environment, we might

expect little variation in fitness along the gradient;

however, most species have a restricted altitudinal dis-

tribution, suggesting that there must be limits to adap-

tation (e.g. Bridle & Vines, 2007). It is also possible that

the environment imposes constraints on the maximum

fitness that cannot be overcome by adaptation. For

instance, fundamental thermodynamic constraints may

lead to lower population growth rates in cold-adapted

than warm-adapted species, even when both are tested

at their thermal optimum (Frazier et al., 2006).

Box 1: The promise of ecological genomics for testing the genetic basis of altitudinal adaptation

At present, genome scans and outlier locus detection are a commonly used approach to detect signals consistent with the

action of divergent selection between populations (Schoville et al., 2012). Perhaps the most serious limitation of this approach

is that – by definition – it detects loci showing elevated between-population differences. Adaptive divergence, however, does

not always involve large allele frequency changes, especially for quantitative traits which can be influenced by many loci and

where interactions between loci can be more important than additive effects (e.g. McKay & Latta, 2002; Le Corre & Kremer,

2012). A second hurdle in nonmodel organisms is that the actual target of selection will (mostly) not be the outlier locus itself

but rather a locus linked to it. Without a well-annotated reference genome, it will be difficult to identify nearby candidate

genes of known function. Still, the detection of outlier loci, even if they remain anonymous, may provide a relatively cost-

effective and tractable way to gauge the extent of putatively adaptive differentiation between populations that may be relevant

for designing conservation and management strategies (but see Allendorf et al., 2010 for additional limitations and caveats).

In recent years, genome-scale analyses have become increasingly possible also in nonmodel species. Using next-generation

sequencing of reduced representation libraries (e.g. restriction site associated DNA; Baird et al., 2008), for example, tens of

thousands of single nucleotide polymorphisms (SNPs) can be identified and genotyped at moderate cost and without the need

for a reference genome (Stapley et al., 2010). These data offer promising new opportunities to investigate the genetic basis of

particular phenotypic traits, for example, using association mapping in natural populations without known pedigrees (Slate

et al., 2010; Stapley et al., 2010). Once adaptively relevant variation has been identified, the frequency of particular variants

can be monitored in space and/or time and related to environmental changes. Ideally, such surveys should be replicated to dis-

tinguish between general and local effects and to follow the fate of genetic variants in different genomic backgrounds. Here,

altitudinal gradients may be particularly valuable because similar gradients are replicated across the globe. Strong barriers to

dispersal may exist also within a mountain range, subdividing species into units that follow largely independent evolutionary

trajectories (e.g. aquatic organisms in different drainages; Keller et al., 2012).

A second feature of altitudinal gradients, namely the small spatial scale at which environmental changes occur, makes them

particularly suited to investigate whether specific genomic architectures are overrepresented in cases where adaptive diver-

gence occurs in the face of gene flow. The chromosomal location of loci involved in divergent adaptation can most easily be

studied if a reference genome from a closely related species is available, but genetic maps can also be constructed by following

the segregation of variants in a pedigree (Slate et al., 2010; Stapley et al., 2010). Of particular interest might be a comparison

of the genomic architectures underlying adaptation along altitudinal vs. latitudinal gradients. The two types of gradients share

some similarities with respect to the observed environmental transitions (e.g. temperature), but these changes occur across

much larger spatial scales with latitude and divergence may consequently be less constrained by gene flow.




Unfortunately, in many cases, it will remain difficult

to perform well-designed experiments that speak

directly to the extent and patterns of local adaptation

along altitudinal gradients, as well as to the link

between particular phenotypes and fitness in a given

environment. These are not easy questions to address,

even in species that are experimentally tractable, and

their study becomes particularly problematic in animals

that cannot be reliably followed through time. How-

ever, recent methodological advances have opened up

exciting new opportunities to investigate potential

adaptation in a more diverse array of species using

molecular approaches (see Box 1).

What is the evolutionary potential of populations alongaltitudinal gradients?The available evidence suggests that there is some

adaptively relevant genetic divergence between popula-

tions and implies that adaptation has occurred in the

past. Whether adaptive change will be possible in the

future will depend upon the availability of relevant

genetic diversity within populations and the rate at

which environmental conditions change (Bridle et al.,

2008). Evidence from the molecular studies surveyed

here suggests that populations may in fact often be

genetically variable at loci with a potential role in adap-

tation to different environments; thus, the loci identi-

fied as outliers (Table 2) – whereas showing large allele

frequency differences between populations – are rarely

fixed for alternative alleles. Often the alleles thought to

be advantageous at low altitudes are observed at lower

frequencies also in high-altitude populations and vice

versa (data not shown). Similarly, for the phenotypic

data, an average coefficient of variation (CV) of 10.7

was estimated across 651 observations for which this

calculation was possible, suggesting some variation

between individuals of a population reared in the same

environment.

Novel genetic variation can be introduced into a pop-

ulation not only through mutation but, perhaps more

relevant for rapid adaptation (e.g. Abbott et al., 2013),

also through gene flow. Altitudinal gradients tend to be

steep relative to the dispersal distance of organisms,

which means that immigrants will often come from dif-

ferent, but nearby environments. In such situations,

the selection coefficients of variants in the different

environments and the rate and symmetry of gene flow

will determine whether between-population differences

are maintained or lost (Lenormand, 2002). Although

gene flow can hinder local adaptation by eroding allele

frequency differences, it can sometimes also facilitate it

by introducing novel and potentially beneficial variants

(Garant et al., 2007). Gene flow from lower towards

higher altitudes, for example, could introduce genetic

variants that have been ‘pretested’ under warmer con-

ditions. Consequently, if conditions at high-altitude

sites indeed tend to become more similar to current

low-altitude conditions under global warming, we

might predict that contemporary gene flow is usually

asymmetrical, occurring mainly from low into high-alti-

tude populations. The symmetry of gene flow has been

assessed along latitudinal gradients (Paul et al., 2011;

Fedorka et al., 2012), but we are unaware of similar

studies along altitude. A mark–recapture study in a but-

terfly, however, found that dispersal was indeed more

common from low- to high-altitude populations, proba-

bly because, at higher altitudes, host plants became

available later in the season (Peterson, 1997).

Does the extent of adaptive differentiation vary betweenspecies and, if so, what factors underlie thesedifferences?The available data show that genetic differences of

potential adaptive relevance exist in a wide range of

species, including highly mobile groups such as birds

where population divergence is potentially maintained

in the face of extensive gene flow. Still, it is important

to keep in mind that the species covered in this review

are probably a nonrepresentative sample and that the

extent of intraspecific adaptive diversity may be low in

many other species. This may be particularly true for

species with narrow altitudinal distributions where

opportunities for adaptive divergence might be more

limited. To understand why local adaptations evolve in

some cases, but not in others, it will be critical to study

a diverse array of species with both narrow and broad

altitudinal distributions. Of particular interest will be

whether some species are somehow predisposed to

evolving and maintaining adaptive differences between

populations. Such a predisposition could involve a

genomic architecture where adaptive traits are shaped

by few loci of large effect and/or clusters of multiple

loci in tight physical linkage, which is expected to facili-

tate adaptation in the face of gene flow (e.g. along alti-

tudinal gradients; Yeaman & Whitlock, 2011).

Conclusions

Our literature survey on local adaptation to altitude

detected extensive phenotypic and genetic diversity

among animal populations sampled along altitudinal

gradients, with several lines of evidence suggesting that

these differences were, in part, adaptively relevant.

Although these conclusions are based upon rather lim-

ited data, we remain convinced that altitudinal gradients

provide very suitable model systems for investigating

local adaptation, albeit systems that have not yet been

used to their full advantage. Furthermore, we anticipate

that methodological advances will enable future studies

to address these phenomena in species that are not

easily tractable experimentally. In the meantime, how-

ever, it seems prudent to assume that most populations

show some adaptive differentiation along altitudinal

gradients, sometimes at very local scales, and that these




adaptively relevant differences should be considered in

conservation and management efforts.

Acknowledgments

This study was carried out in the framework of Gene-

Reach, a project lead by J. Bolliger (WSL) and funded

by the Competence Center Environment and Sustain-

ability, ETH Z€urich, Switzerland. IK would like to thank

O. Seehausen, M. Haesler, K. Lucek, D. Marques and

J. Meier for support and helpful discussion.

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Supporting information

Additional Supporting Information may be found in the

online version of this article:

Figure S1 Genetically based phenotypic changes along

altitudinal gradients for (a) heat tolerance, (b) heat-

shock protein expression, (c) desiccation tolerance, (d)

body length, (e) growth rate, (f) longevity, (g) viability,

and (h) fecundity.

Table S1 List of publications included in the review.

Received 3 May 2013; revised 26 August 2013; accepted 27 August

2013




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