Endocrine
uncoupling
of
the
trade-off
between
reproduction
and
somatic
maintenance
in
eusocial
insects
Marisa
A
Rodrigues
and
Thomas
Flatt
Inmostanimalsreproductiontradesoffwithsomatic
maintenanceandsurvival.Physiologicallythistrade-offis
mediatedbyhormoneswithoppositeeffectsonreproduction
andmaintenance.Inmanyinsects,thisregulationisachieved
byanendocrinenetworkthatintegratesinsulin-like/IGF-1
signaling(IIS),juvenilehormone(JH),andtheyolkprecursor
vitellogenin(Vg)(or,moregenerally,yolkproteins[YPs]).
Downregulationofthisnetworkpromotesmaintenanceand
survivalattheexpenseofreproduction.Remarkably,however,
queensofhighlyeusocialsocialinsectsexhibitbothenormous
reproductiveoutputandlongevity,thusescapingthetrade-off.
Hereweargue—basedonrecentevidence—thatthe
proximatereasonforwhyeusocialinsectscandecouplethis
trade-offisthattheyhaveevolvedadifferent‘wiring’ofthe
IIS-JH-Vg/YPcircuit.
Address
DepartmentofEcologyandEvolution,UniversityofLausanne,UNIL
Sorge,Biophore,CH-1015Lausanne,Switzerland
Correspondingauthor:Flatt,Thomas(thomas.flatt@unil.ch)
‘‘Hormones are natural candidates for physiological mechanisms that can give rise to antagonistic pleiotropy... When, for example, hormones mobilize theorganismforreproduction,thetransferofresources fromsomaticfunctionstoreproductivefunctionscanbe expectedtoproducetrade-offsbetweenthe correspond-ingfitnesscomponents,survival,andfecundity, respec-tively.’’
Finch andRose (1995)[17]
Introduction
Inmanyorganismsoneobservesanegativerelationship (a ‘trade-off’) between reproduction versus somatic maintenanceandsurvivalability;increasedreproduction
thus exacts costs in terms of reduced maintenance (e.g.,stress resistance,immunity) andloweredsurvival [1,2,3,4,5].This trade-offhasbeenwelldocumentedat the phenotypic, physiological or quantitative genetic level innumerous speciesand representsamajor con-straintuponphysiologyandtheevolutionoflifehistories [2,3,4,5,6,7].
Atraditionalpopulationgeneticexplanationforsuch trade-offsistheexistenceofalleleswithantagonisticpleiotropic effects upon fitness components (life history traits), for exampleallelesthatpromotegrowthand/orreproduction attheexpenseofsomaticmaintenanceandsurvival;such allelescontributetonegativegeneticcorrelationsbetween reproductiveandmaintenancetraits[6,7].Atthe physio-logicallevel, theclassicalinterpretation ofthe reproduc-tion-maintenancetrade-offisthattheenergeticallycostly process of reproduction ‘competes’ with the energetic demands of somatic maintenance and survival [2,3,4,5,8].Theseinterpretations—geneticversus physi-ological—areobviouslynotmutuallyexclusive[4,5,7]. Althoughalargebodyofliteraturesupportsthenotionof energyorresourceallocationtrade-offs[2,3,4,5,8],recent evidence suggests that under some circumstances the fecundity/longevitytrade-off canbe‘decoupled’or ‘bro-ken’[3,4,5,9](Herewerefertothistrade-off,more gener-ally, as the ‘reproduction-maintenance’ trade-off since survival/longevityareafunctionof somaticmaintenance processes, including repair, stress resistance, immunity, etc.). Most examples of such a ‘decoupling’ come from laboratorystudiesoflarge-effectmutantsortransgenesin model organisms (e.g., Caenorhabditis elegans, Drosophila melanogaster); however, in at least some of these cases, the ‘‘breaking’’ofthetrade-offislikely tobeartifactual or illusory[4].For example, certainlong-lived C.elegans mutants of the insulin-like receptor gene daf-2 do not exhibit any measurable fitness costs (e.g., in terms of fertility), but lose outwhen competed againstwildtype worms[4].Thebestevidenceforareal,naturallyoccurring uncouplingof the reproduction-maintenancetrade-offis providedbyeusocialinsects(ants,termites,bees,wasps): inmanyhighlyeusocialinsectspecies,queenscanachieve enormous reproductive output while at the same time beingextraordinarilylong-lived[10,11,12,13](Figure1). Herewediscusspossibleproximateexplanationsforwhy queens in highly eusocial insects, in contrast to other insects, might be able of ‘decoupling’ the trade-off
http://doc.rero.ch
Published in "Current Opinion in Insect Science 16(): 1–8, 2016"
which should be cited to refer to this work.
between reproductionversusmaintenanceand survival. Based on recent evidence from honey bees and ants [14,15,16]wearguethatthisislikelyduetoadifferent ‘wiring’,i.e.changesintheregulatoryarchitecture,ofthe endocrinenetworkthatunderliesthephysiological regu-lation of the reproduction-maintenance trade-off. We concludethatabetterunderstandingofproximate mech-anisms might make an important contribution to our understanding of ultimate causation in lifehistory evo-lution [5,17,18,19,20,21,22,23,24,25,26,27,28,29].
Endocrine
regulation
of
the
reproduction-maintenance
trade-off
Numerous studies in many species indicate that at the physiological level various hormones can have opposite regulatoryeffectsongrowthandreproductionversus main-tenanceandsurvival;suchhormonesmightthusrepresent endocrinekeymediatorsofthereproduction-maintenance trade-off[5,17,18,19,20,21,22,23,24,25,26,27,28].Although themoleculardetailscandiffersubstantiallyamongtaxa,in
many species the reproduction-maintenance trade-off seems to begoverned byaneuroendocrine-reproductive ‘axis’(orprobablymoreaccurately—duetofeedforward and feedback loops — a ‘network’) [5,18,19,20,21, 25,29,30].
InthenematodeC.elegans,variousinsectsincluding Dro-sophila,andthemouseMusmusculus,environmentalcues and dietaryinputsare integratedbythecentralnervous system (CNS) and relayed by endocrine signals which activatea‘pro-reproductive,pro-agingmode’;conversely, downregulationofthiscircuitryswitchesthesystem toa ‘pro-maintenance, pro-survival mode’ at theexpense of growthand/orreproduction[18,19,25,29,30].Across spe-ciesthemostevolutionarilyconservedcomponentsofthis network seem to be those involved in insulin/IGF-like signaling(IIS);acrossseveralmodelandnon-model organ-isms downregulation of IISis associated with extended lifespanandincreasedstressresistancebutreducedgrowth and/orreproduction[18,19,20,21,24,29,30]. Figure1 (a) (b) Nutrition ILPs IIS JH Nutrition ILPs IIS JH Vg / YPs Vg / YPs ? ? ? ? ?
Reproduction Somatic maintenance Reproduction Somatic maintenance Current Opinion in Insect Science
Modeloftheendocrineregulationofthereproduction-maintenancetrade-offin(a)non-socialinsectsversus(b)highlyeusocialinsects.Arrows
indicateactivation;stopbarsrepresentrepression;anddottedlinesdenotetheabsenceofaneffect.Solidversusdashedlinesrepresent
regulatoryalternatives;questionmarksdenoteunknownorpoorlyunderstoodrelationships.(a)Inmostnon-socialinsects,highnutritionalinput
stimulatestheproductionofinsulin-likepeptides(ILPs).ILPsactivateinsulin/insulin-likegrowthfactorsignaling(IIS),whichinturnactivatesthe
productionofjuvenilehormone(JH).IISandJHstimulatereproductionattheexpenseofmaintenance,eitherinterdependentlyand/or
independently.JHactivatestheproductionofvitellogenin(Vg)and/oryolkprotein(YP).Vg/YPpromotesreproductionattheexpenseof
maintenance.(b)Inhighlyeusocialinsects,highnutritionalinputisthoughttostimulateILPproduction,butinhoneybeesandpotentiallyalso
otherspeciesthisrelationshipmightbereversed.ILPsactivateIIS,andinseveralspecieslowIISisassociatedwithlongqueenlifespan,as
expectedbasedonnon-socialinsects.IISlikelyactivatesJHproduction,butthisstillremainspoorlyunderstood.Dependingonthespecies,JH
eitherretainsitsancestralgonadotropicfunctionoritsfunctionhasbeenaltered(e.g.,JHreducesreproduction);yet,inallcaseswehave
reviewedJHseemstonegativelyimpactsomaticmaintenanceineusocialinsects.Insomespecies,JHeitherpromotesVg/YPproduction,inhibits
it(e.g.,inhoneybeesJHandVgareinvolvedinadouble-repressorloop),ormightbedecoupledfrompromotingVg/YPsynthesis.Again
dependingonthetaxon,Vg/YPcaneitherpromotereproductionornot.Atleastinhoneybees,Vg/YPseemtopromotesomaticmaintenanceand
longlife;inseveralspecies,Vg/YPhasbeenco-optedfordifferentnon-classicalfunctions,includinginsocialbehavior,castedeterminationand
polyphenism.Thus,especiallyineusocialinsects,the‘wiring’oftheJH-Vg/YPpartofthenetworkseemstobeevolutionarilyhighly‘flexible’or
‘labile’;theevidenceathandsuggeststhatmodificationsofthispartofthecircuitrycanmakeasignificantcontributiontotheuncouplingofthe
reproduction-maintenancetrade-offinhighlyeusocialinsects.
In rodents and other mammals,for example, the hypo-thalamic–pituitary–gonadal (HPG) and somatotropic (growth hormone [GH] — insulin-like growth factor 1[IGF-1])signalingaxeshaveemergedasmajor media-tors of the trade-off between growth and reproduction versus maintenanceand survival [19].Interestingly, in Drosophilaandotherinsectsafunctionallyparallel endo-crineaxisintegratessignalsbetweenthebrain,endocrine glandsattachedtothebrain(thecorporaallataandcorpora cardiaca; equivalent to the hypothalamus/pituitary), the fat body (equivalent to mammalian liver and adipose), and the gonads. This system integrates IIS, lipophilic hormonesdownstreamofIISwhichactasgonadotropins (mainly juvenile hormone [JH], but also 20-hydroxy-ecdysone [20E]), and the yolk precursor vitellogenin (Vg) or yolk proteins [YPs] [18,20,22,23,24,25,26,27, 29,30,31]. Likewise, a functionally parallel signaling axisinC.elegansconnectsneuroendocrinesignals includ-ingIISand TGFb signalswith steroidhormones (dafa-chronicacids) and — as of yet unidentified —gonadal signals[18,21,29,30].
The
IIS-JH-Vg/YP
signaling
network
in
non-social
insects
Tounderstandthepossibleproximatereasonsforwhythe reproduction-maintenancetrade-offcanbeuncoupledin eusocialinsects [14,15,16],we must firstdiscusssome detailsoftheIIS-JH-Vg/YPaxisinnon-socialinsectsand otherinvertebrates.
AtthelevelofIIS,manyexperimentsusingmutantsand transgenes in C.elegans andDrosophila haveshownthat downregulationofIISpathwaycomponentsextends life-span and increases stress resistance [18,20,21]. These changesareoftenaccompanied byreduced growthand/ or decreased fertility, even though in some cases the lifespan-extending effects can be genetically separated fromthenegativeeffectsongrowthand/orreproduction [18,20,21]. Similarly, ablation of the insulin-producing cells (IPCs) in the parsintercerebralis of theCNS in D. melanogaster and the linden bug Pyrrhocoris apterus extendslifespanattheexpenseof fecundity[20,24]. Inresponseto IISthecorporaallata(CA)glands(or the singlecorpusallatumofD.melanogaster)behindthebrain produce JH, ahighly ‘pleiotropic’sesquiterpenoid with effects on development, metamorphosis, reproductive maturation, fecundity, stress resistance, immunity and lifespan[17,18,20,25].Severallevelsofevidenceindicate thatJHisamajor‘pro-aging’gonadotropinthatmediates thereproduction-maintenancetrade-off.First,long-lived, sterileD.melanogastermutantsoftheinsulin-likereceptor InR(theflyhomologofC.elegansdaf-2)areJH-deficient, and treatmentof thesemutants with aJHanalog (JHa) restores(shorter)wildtypelifespanandpartlyrescuesthe fertilitydefect[18,22,25].Second, surgicalor transgenic ablation of the CA glands in grasshoppers (Anacridium,
Schistocerca,Locusta),themonarchbutterfly(Danaus plex-ippus),thelindenbugandfruitfliesextendslifespanand promotes somatic maintenance at the cost of reduced fertility[22,23,24,25,31].Third,treatmentofwildtypeD. melanogaster with JHa promotes fecundity but shortens lifespanandincreasesoxidativestress[25,26].Fourth,JH isapotent suppressor ofinnate immunityin Drosophila andotherinsects [16,25,32].
One of theprincipalgonadotropic functions of JHis to regulatetheproductionofvitellogenin(Vg),aneggyolk precursorprotein,andofYPs[14,25,33,34,35].Owingto theirimportantroleinlipidstorageandtransport, ithas been hypothesized that Vgs and YPs might play an important role inlifespan regulation [36]. Insupport of this notion, the C. elegans Vg genes vit-2 and vit-5 are regulatedbyIIS,andRNAiagainstthesegenespromotes longevity[37].Similarly, RNAi againstVgin thelubber grasshopper (Romaleamicroptera) causesovarian growth arrestandextendslifespan[38].Althoughthe Drosophi-la YP genes yp1, yp2, and yp3 are not direct sequence homologs of the vitellogenin (Vg)genes of other insects, Drosophila YPs are thought to play the same storage proteinroleasVgs[33,39,40];ypmutationsaffect ovari-olenumberandfertility,and expressionofYPsis nega-tivelycorrelatedwithDrosophilalifespan[41].However, thepotentialeffectsofYPRNAionlifespaninfruitflies havenotbeeninvestigatedyet.Finally,transgenic over-expressionoftheDrosophilaVg-likegene(CG31150,also called cv-d) and of the (exogenous) honey bee (Apis mellifera)VggeneintheflydecreasesDrosophilalifespan [39]. Thus, although the mechanistic details remain poorly understood, Vgs/YPs seem to be intimately in-volvedin thereproduction-maintenancetrade-off. Together,the evidence available to date shows that in non-socialinsectsandotherinvertebratestheIIS- lipo-philichormone(e.g.,JH)-Vg/YPsignaling networkhas pervasive—likelyevolutionarilyconserved— pro-repro-ductive and pro-aging effects. Downregulation of this network,for example inresponseto (dependingon the species)low nutrientavailabilityorotherenvironmental changes (e.g., temperature, photoperiod), switches the physiologicalstateoftheorganismtoapro-maintenance, pro-survival ‘mode’ at the expense of growth and/or reproduction [29]. Howthen— giventhat thequeens ofhighlyeusocialinsectspecieshavemanagedtoescape thereproduction-maintenancetrade-off —isthis endo-crinecircuitry‘wired’in theseinsects?
Modified
regulation
of
the
reproduction-maintenance
trade-off
in
highly
eusocial
insects
Basedonthreerecentstudiesinhoneybeesandants,by Corona et al. [14], von Wyschetzki et al. [15], and Pammingeretal.[16],apictureisbeginningtoemerge which suggests that the reproduction-maintenance
trade-offcanbedecoupledbychangesintheregulatory architecture oftheIIS-JH-Vg/YPnetwork.
Inhoneybees,incontrasttomostinsects,JHandVgtiters are not positively but inversely correlated. In workers, there is a negative (‘double repressor’) feedback loop between JH and Vg wherebyVg is high and JH islow instress-resistantnursebees,whereasJHishighandVg lowinthemorestress-susceptibleforagerbees:increased JHlevelsanddecreasedVgtiterscausenursebees(inthe hive,characterizedbyhighpollenintake,corpulent bod-ies,highstressresistance)totransitiontobecomeforager bees (characterized by high nectar intake, lean bodies, lowstressresistance)[29,42](alsoseeRueppelletal.,in this issue). The correlationbetween high JH titers and increasedstresssusceptibilityinworkerbeesisconsistent withfindingsfromnon-socialinsects,suggestingthatJH actsasa‘pro-stress’,‘pro-aging’hormone(seeabove).In contrast,Vgappearstopromotesomaticmaintenanceand survival,unlikethehypothesized‘pro-aging’roleofVgs/ YPs in non-social insects: indeed,Vg RNAi knockdown assays in the honey bee demonstrate that Vg acts as a major antioxidant, protecting workers against oxidative stress-induced mortality[29,43,44].
The above findings have led to the suggestion thatVg might also be involved in regulating queen lifespan [29,43,44].Consistent withthisnotion,queensshowan age-dependentdropinJH,accompaniedbyanincreasein Vg levels,andaremoreresistanttooxidativestressthan workers [14]. (Two noteworthy side comments in this context are:(i)incontrast to oldqueens,JHiselevated inyoungqueens,andthisisassociatedwithmatingflight activity;afterthematingflights,theyonlyflyagainwhen theyleavetogetherwiththeswarm;shortlybefore swarm-ing,Vglevelsaredecreasedandoogenesisisreduced;and (ii)increasedJHlevelsarealsoseenindronesbeforethey leavethehivetoformdroneaggregations,andJHtitersin drones parallel the levels of Vg; titers of Vg are low, however,anditsfunctionalroleindronesremainsunclear [45,46].) Oldqueensrelative toold workersalsoexhibit downregulationofaninsulin-likepeptide (ILP)andtwo insulinreceptors,whichmightperhapsbeinlinewiththe pro-survivaleffectsofreducedIISobservedinother spe-cies [14].Thisdownregulation might bedue to low JH titersinolderqueenssincetreatmentofqueenswithJHa increasesILPexpression[14].AsimilarJH-ILPfeedback isobservedinCA-ablatedflieswhichshowdownregulation ofILP6(however,incontrasttootherILPs,ILP6promotes rather than decreases lifespan), indicating that JH pro-motesILP6expression[31].
GiventheexistenceofaJH-Vgdouble-repressorfeedback loop inworkersandthefactthatVgsynthesiscanoccur independentofJHinhoneybees,afundamentalquestion thus concerns evolutionarydifferences amonginsectsin the ‘coupling strength’ between JH as a gonadotropic
hormoneandthesynthesisofVg,whichistypicallytaken asageneralproxyforfemalefecundityandfertility.Akey differencebetweenhighlyeusocialandnon-socialinsects isthatthelatter,especiallyspeciesthatliverelativelylong, exhibit(oftendiet-dependent)reproductivecycleswhose initiationrequiresagonadotropicsignal(typicallyJH,but in some dipterans also ecdysone) which induces Vg/YP productioninthefatbody.Inmarkedcontrast,Vg produc-tionandegglayingiscontinuousinthequeensofhighly eusocial bees, wasps,and ants, so that the reproductive process—onceithasbeentriggered—canessentiallyrun constitutivelyduringanindividual’sreproductivelifespan. Inthehoneybee,forexample,JHstillplaysagonadotropic role,butthisfunctionhasbeenshiftedfromtheadulttothe pharateadultstage,i.e.thetimeshortlybeforethequeen shedsthepupalcuticleandemergesfromthebroodcell: duringthepharatestage,JHtitersincreaseinqueensand applicationofJHinduces Vgsynthesis[47,48].Itisthus tempting to speculate that during the evolution of ad-vanced insect eusociality the gonadotropic function of JHinqueensmighthaveundergoneaheterochronicshift andthatthisshiftmighthaveremovedevolutionary con-straints on the JH-Vg/YPnetwork, thereby ‘freeing’JH and/orVg/YPtotakeonotherfunctionalroles(e.g.,flight, oxidativestressresistance,etc.).Whilesuchascenariois not yet well supported by evidence, its plausibility is strengthenedbythefactthatinlepidopteransthecoupling strengthofJHandecdysonetoVg variesamongspecies dependingontheirparticularlifehistory[49].
Basedonthesefindings,Coronaetal.[14]haveproposeda model that might explainthe uncoupling of the repro-duction-maintenancetrade-off inhoney bees.Together with work byGro Amdam’sgroup [43,44], their model makesthefollowingassertions[14]:(a)asinotherspecies, downregulationofIIShasapro-longevityeffectinbees, but the typical relationship between nutrition (which normally promotes IIS) and IISis reversed so that the highnutritionalstatusofqueensinhibitsILPproduction and/orsecretion;(b)incontrasttomostotherinsects,the typical gonadotropic functionof JH hasbeenalteredin bees: the typical, positive JH-Vg coupling has been shifted to the pharate adult stage, whereas in adult (non-pharate) queensVgsynthesiscanrunlargely inde-pendently of JH input, and high JH can even repress vitellogenesisandactasasuppressorofVg;(c)Vgplaysa majorroleasapro-maintenanceantioxidant;and(d)the relationshipbetweenJHandIISismediatedbyVgwhich mightnow actasacentralendocrinesignalingmolecule ratherthana‘simple’yolkproteinprecursor.Thisbeing said,amajorcaveatisthatnothingisknownyetaboutthe putative role of Vg as asignalingmolecule: this clearly requires in-depthfutureinvestigation.
Hence,thereareatleastthreeaspectsoftheIIS-JH-Vg/ YP networkthataredifferentinthehoneybee as com-paredtonon-socialinsects:thedisconnectbetweenhigh
nutritionandIIS;thealteredgonadotropicroleofJH;and thepro-survival(ratherthanpro-aging)functionofVg(or ofYPsingeneral).Indeed,ithasbeenfoundthatVgRNAi decreases bee worker lifespan [44], and the data from queens [14] are consistent with a lifespan-promoting effectsof Vgas well.
Asecondrecentstudyreportinganalternativeregulation of thereproduction-maintenancetrade-offisduetovon Wyschetzkietal.[15](alsoseeOettlerandSchrempf,in thisissue).Inthispaper,theauthorsexaminewhole-body transcriptomes of differently aged queens of the ant Cardiocondyla obscurior. By comparing gene expression patterns in theanttoage-related expressionchangesin D.melanogastertheyfindmajorsimilaritiesin age-depen-dent transcriptionbetween thesespecies. However, for manytranscriptstheage-dependent expressionpatterns go in opposite directions between ants and flies: as comparedtoyoungqueens,oldqueensupregulate repro-ductivegenesbutdownregulatemetabolicgenes, where-astheoppositepatternisseeninfemalesflies[15].In terms of an involvement of IIS and JH signaling, the authorsdetecteddifferentialexpressionofNlaz(a homo-log of vertebrateapolipoprotein D [APOD]),which has previouslybeenshowntoaffectDrosophilalifespan; Ade-nylylcyclase 76E(Ac76E),whichrepresentsadirect tran-scriptional target of the major IIS (forkhead Box O) transcription factor foxo and which has been shown to affectJHproduction;andofaputativeJHbindingprotein (homologofDrosophilaCG34316).
IncontrasttothepaperbyCoronaetal.[14],however,this study does not find evidence for a major role of Vg in regulating fecundity or longevity in C. obscurior: the ortholog of the honey bee ‘vitellogenin-like’ gene GB52464wasmoderatelydownregulatedinoldermated queens. Similarly, theauthors observed upregulationof InRinolder,morefertilequeens[15],whichmightbe seenas beinginconsistent withthemodel proposedfor the honeybee queen,positing adownregulationof IIS [14].On theother hand, theupregulation of InR could actually be consistent with downregulation of IIS:in Dro-sophila,downregulationofIIScausesincreasedactivityof foxowhichinturncausesthetranscriptionalupregulation of INR protein atthe cellmembrane [50]. Ittherefore remainsunclearwhether thesefindings(especially with regardtoVg)possiblymeanthatdifferenteusocialinsects might have evolved alternative waysof uncoupling the reproduction-maintenancetrade-off(alsoseebelow). Inthethirdstudy,Pammingeretal.[16]showthat long-lived queens of the ant Lasius niger likely defy the reproduction — immunity trade-off by decoupling the gonadotropic versus immunosuppressive effects of JH. The authors find that — in contrast to its typical in pro-reproductive effects in most other insects — JHa treatment decreasesfecundity, increases thenumberof
non-vitellogenicoocytes,andreducesinvestmentin ma-ternalcare[16].Incontrast,andsimilartootherinsects, JHadecreasestheactivityoftheimmuneeffectors phe-noloxidase (PO) and prephenoloxidase (PPO) and reducessurvivaluponpathogenexposure.Thisalteration oftheroleofJHwithregardtoreproductionissimilarto thatreportedfor honeybees[14],suggesting that mod-ifications(e.g.,separation)ofJHfunctionsmight contrib-uteto the uncoupling of thereproduction-maintenance trade-offinimportantways.Thus,byreleasingJHfrom itspro-reproductiverole,L.nigerqueensmightbeableto avoidtheimmuno-suppressiveeffectsofJH.However,a majorcaveatisthattheauthorsdidnotquantifyJHtiters andmeasurewhetherandhowJHatreatmentaffectsJH signalinginthissystem.Forexample,JHaapplicationcan have unintended pharmacological side-effects when its dosage is too high, and it is thus important to perform dose-responseexperimentswithinthenormal physiolog-icalrange.
Astheauthors discuss,theirmodelofalteredor ‘separa-ble’JHfunctionsmightbeplausiblewhenconsideringa broader phylogenetic view: in bumblebees, wasps and primitivelyeusocial bees,whichare typically character-izedbyhighreproductiveoutput,elevatedJHtiters,and relatively short queen lifespans, JH acts as a ‘classical’ gonadotropin (as in most other, non-social insects) [51,52],whileinantsofthegenusDiacammareproduction is associated with both low JH and increased lifespan [53,54].Yet,asPammingeretal.[16]note,JHdoesfunction asagonadotropinwithstimulatoryeffectsonVg expres-sionin relatively long-lived queens of thefire ant Sole-nopsisinvicta[51,52].Similarly,JHatreatmentstimulates Vg1 and Vg2 gene expression in queens of the seed harvester ant(Pogonomyrmex rugosus) [35],a genusthat typically exhibits long queen lifespans. Thus, whether Solenopsis and Pogonomyrmex ants (or different eusocial insectsmoregenerally) haveevolveddifferentsolutions to theproblem of uncoupling the reproduction-mainte-nancetrade-offremainsunclearbutseemslikely[16]. These considerations, and our above discussion of the timingshift of the gonadotropic function in honey bee queens, highlight the importanceof analyzing the evo-lution oftheIIS-JH-Vg/YP networkfrom aproper phy-logeneticpointofview.Forexample,amajorpointinthis contextisthedistinctionbetweenprimitivelyandhighly eusocialinsects(i.e.,primitivelyeusocialbeesandwasps versus highly eusocial bees and ants): in contrast to primitivelyeusocialinsects,highlyeusocialbeesandants are characterized by the fixation of caste fate during postembryonicdevelopment,i.e.whatWilsonand Ho¨ll-dobler [55] have called the ‘point of no return’ in the evolution of Hymenopteran eusociality (for a recent reviewoftheendocrinemechanismsunderpinningcaste differentiationsee[56]).Itisthusanattractivepossibility thattheirreversibletransitionto fixedcastephenotypes
might have removed constraints on the IIS-JH-Vg/Yp regulatorynetwork,therebyallowingforthe‘uncoupling’ of the reproduction-maintenancetrade-off.Another im-portantpointisthatmostprimitivelyeusocial Hymenop-tera, especially those from temperate climates, have annual colonies, with the queen dying at the end of the season andthus notlivinglonger thantheworkers; in contrast,highly eusocial species haveperennial iter-oparouscolonies.Inthefutureitwillclearlybecrucialto conduct broad-scale comparative studies across non-so-cial, primitively eusocial,and highly eusocialinsects to gainanimprovedunderstandingoftheuncouplingofthe reproduction-maintenance trade-off in eusocial insects and beyond.
‘‘Ourhopethatafewpathwayswillbeshowntomediate life history variation in most animals should also be temperedbytherealizationthatthecausesofvariation in traitssuchas growthrate,fertility, andsurvivalare oftenmorecomplexthanthecausationoftraitssuchas digitnumber,limbcomponents,andbodyaxes...That doesnotmeanthat...IISisnotimportantinmediating trade-offs...Itveryprobablyplaysakeyrole.Butitdoes meanthatdissectingthecausesinfluencingsuchtraitsis amajorexperimentalchallenge.’’
Stearns(2011)[57]
Conclusions
Severalrecentstudiessuggest thatwemight beableto begintounderstandtheproximatereasonsforwhyhighly eusocialinsectshavemanagedtodefythe reproduction-maintenance trade-off. These studies indicate that the functions of endocrine regulators of this trade-off have beenalteredinhoneybeesandseveralantsascompared to non-social insects. At the same time, the picture emerging from these studies indicates that different eusocial insects might have evolved distinct proximate solutionstotheproblemofdecouplingthetrade-off.For instance, thevarious functionsof JH areunlikely to be conservedamongeusocialinsectsand,toquote Pammin-geretal.[16],JH‘canact asaflexible toolin regulating key systemic processes in different genera’. A similar argumentcanbemadeforvitellogeninwhosetraditional functioninreproductionseemstohavebeen‘remodeled’ in different eusocial insects, including roles in social organization, behavior, stress resistance, and lifespan [58].Giventhecomplexities ofendocrine physiology, thismightbeasoberingtake-homemessage[57],butitis certainly noteworthy that a growing number of studies identifies the same key players to be involved in the physiological regulation of social insect life histories (including caste determination and polyphenism) and the uncoupling of the reproduction-maintenance trade-off.Obviously,itisstillearlydaysforinvestigationsinto the mechanisms underlying trade-offs [5]; we remain convincedthatfuturestudies,suchastheoneswehave
discussed here [14,15,16], hold greatpromise for illu-minating the uncoupling of the reproduction-mainte-nance trade-off in eusocial insects. There is a major needformorecomparativestudiesoflifehistory physiol-ogy across species, and for more dialog between life history theoristsand physiologists[3,5,57].
Acknowledgements
WethankTuckFinchandMichaelRose[17]forinspiration,andKlaus
HartfelderandJudithKorbforveryhelpfulcommentsonthemanuscript.
ThispaperwaswrittenaspartoftheresearchcarriedoutbytheDFG
CollaborativeResearchUnit(RU)‘SocialityandtheReversalofthe
Fecundity-longevityTrade-off’(DFGFOR2281),andwethankthe
membersoftheRUforstimulatingdiscussions.Duetospacelimitations,
wecouldnotalwaysciteprimaryresearchpapersbuthadtocitereviews
instead;weapologizetoourcolleagueswhoseworkwecouldnotdiscuss.
OurworkwasfundedbytheSwissNationalScienceFoundation(SNSF)
(grantsPP00P3_133641and310030E-164207toT.F.).
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