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Principles and general concepts of adaptation
ENVmONhlBNTAL
RESEARCH
Principles
2, 304416
and
( l%?))
General
Concepts
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Adaptation1
C. LADD PROSSER
My assignment in this conference is to present some of the principles of physiological adaptation from the viewpoint of a general biologist. First, I wish to present some definitions in the hope that this conference may agree on a common terminology. It is unfortunate that in many standard works; for example, the Handbook of Physiology (3, 5, 15, IS), certain words are used by different contributors with very different meanings. I hope to show that the general terminology developed by comparative physiologists is applicable to human physiology. Further, while most of my examples will be drawn from temperature stresses,the terminology is equally applicable to such other environmental parameters as hypoxia. osmotic and ionic stresses, and nutritional factors. The word “adaptation” has many meanings and should be defined in each context in which it is used. If I were to ask 100 biologists for the meaning of adaptation, I might get 100 different definitions. It may well be that this word is no longer precise enough for serious usage. For some, adaptation refers to those properties (usually anatomic) which have been selected over long periods of evolution to permit survival. For others, adaptation refers to the rapid decay of an excitatory process, as in srnsory adaptation, For still others, adaptation refers to any ltomeostatic reaction, In the present discussion, adaptation refers to any property of an organism which permits physiological activity and survival in a specific environment; adaptation is characteristically related to stressful components of the environment although it may relate equally well to a total environment. Adaptive characters have clrrrrtic basis but may be expressed according to environmental needs. A response is a direct reaction, either adaptive or nonadaptive to an cnvironmental stimulus, It is usually, but not necessarily, reversiblr. An example would be a direct change in rate of a chemical reaction with temperature, as in a Ql,, effect. Adaptive variations may be measured in individuals. populations, or higher taxonomic categories. They include anatomic. physiologic, and biochemical characteristics of individual organisms which relate thcsc, individuals adaptively to a specific environment. In an evolutionary sense, only those v,ariations that arc adaptive are retained. Natural selection is the only known mrchanism for fix:rtion of adaptive variations and forms the basis for speciation.
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,\ physiological concept of biological species may be derived as follows: If no two species can occupy the same ecological niche or the same geographic range throughout their life cycles, it follows that every species must be uniquely adapted to its particular niche and range. Hence, if we could quantitatively describe the physioIogica1 adaptedness of a species to its ecological niche and geographic range, we would have a truly meaningful description of the species. One of the goals of environmental physiology is to achieve some understanding of the molecular basis for natural sckbction. However in the contest of this conference adaptive variations are considered for individuals, not sp(bc:ies. “Homeostasis“ is a term which has been broadened from the original meaning of Cannon to refer to self-stabilizin g states or organisms, societies, and computers. Physiologically. vv;c’ can use “homc~ostasis” not only for maintenance of constancy of the internal c~nvironmcnt, biit also for maintenance of constancy of energctics, of work capacity, of self-identity, and of independence of the external environment. The (pence of living things is to be at once apart from their environment rind a part of the environment. Homeostnsis describes the sum total of propertic’s contributing to the “apartness” of inclividuals.
The goals of cnv-ironmcntal physiolog! ma!~ be listed sequentially in three categoric3 : .l. To describe adaptive variations in or ganisms-whether individuals, populations, races, or species. Much remains to be done in this dcscriptivc phase with respect to human adaptive variation. It is not always easy to identify how a given character is adaptive-for example, pigmented skin in Negroes. Biologic meaning of some characters may he found onh in genetic linkage and plciotropism, as in sickle-cell anemia. 2. To discover the origin of such variations as are described-whether genetic or cnvironmcntally induced. Genetically determined variation is based on selection from random variation and is transmitted in the genotype. Environmentally induced, or nongenetic, variations may bc transitory for individuals or may be transmitted culturally from generation to generation. Genetically determined variation can generally he distinguished from nongenetic by acclimation or acclimatization supplemented by breeding experimcnts. Acclimation consists of those conpensatory changes which occur in intlividuaIs mlder controlled laborator)- conditions whcrc only one environmental parameter is varied, for example temperature or photoperiod. Acclimatization consists of those adaptive changes which occur under natural conditions when multiple factors vary, as in diffcrcut climates, seasons, and geographic conditions. For csample. the changes occurring in a rodent out-of-doors in the winter differ from the changes in similar animals in a cold room. Identification of critical environmental strcssors is not ahvnys clear when th(y ar(x multipletemperahue, photoperiod. nutrition. and others. Acclimation in man is difficult to obtain. although acclimatization has been milch studied. Prolonged czposures in d~~comprc~ssion chambers have provided
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a basis for comparing acclimation to low pressure with acclimatization in high mountains. Acclimation to heat or cold has been studied with periodic, repetitive, or l-week exposures in temperature chambers, but how this differs from continuous exposure for long times at a constant temperature is not established. Life in the Arctic or Antarctic is very different from that in a cold room. Evidence is now accumulating that animals from very mliform environments may lose their capacity for acclimation while those which live in highly variable environments have maximal capacity for acclimation. This has practical importance for the adaptability of transplanted populations and species. The genotype sets the limits within which environmentally induced variation can occur, that is, the range of phenotypic variability. A major task in human biology is to separate the two causes of variation-genetic and environmentally induced. 3. To explain adaptive variation at all levels of organization. This includes a description of feedback interaction between environment and organism-for example, the regulation of synthesis of specific proteins by environmental stressors. Explanation of variation in biochemical terms may elucidate the molecular basis for natural selection. CRITli,RI.A
OF
PHYSIOLOGIC
VAKIATION
Criteria of physiologic variation may bc grouped into four broad categories ( 18). 1. Internal state for a given parameter as a function of that parameter in the environment. This is the essence of homeostasis and may occur in either of two patterns or a mixture of these: Conformity of internal state to the environmentul stute. Familiar examples are poikilothermic and poikilosmotic animals in which temperature or osmotic concentration in body fluids and tissues rises and falls with these parameters in the external environment. Conformity is homeostatic in its broader meaning, in that enzyme systems of conformers can function over a wide range of internal environments. In man and other naked mammals, and in aquatic mammals, the skin temperature can vary widely according to cnvironmcntal temperature, and enzymes of skin may be adapted to be active over a much wider temperature range than corresponding enzymes of liver. Regulation or constclnuy of intetnal stnte. As the environmental parameter changes, feedback control reactions tend to maintain internal constancy; at some limitinq c gradient, these control reactions fail and the internal state changes abruptly. Familiar examples are maintenance of constant body temperature, constant blood sugar, and constant sodium-potassium ratios in body fluids. The cost of adaptation by internal regulation is considerable, but internal constancy permits body functions over a wide environmental variation. In general, conformers tolerate wider internal variation, and regulators, wider external variation, with respect to a given parameter. Many animals show combinations of the two patterns, regulation of one parameter or in one environmental range and conformity in another, or regulation at one stage
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in development or time in a life cycle. A hibernating mammal is a tempcraturc conformer over a certain range when torpid, a regulator to relatively internal temperature when active. A related measure of variation is the rate of recovery of internal state after For example, the pattern of recover). drviation due to a stressing espcricnce. of normal water load after dehydration is specific to a species. 3. Rat(- functions. Any biologic function that can bc measured as ~1 rate of adaptive variation when with respect to time may br used as ;I criterion tested in different environmental states. ~hc time course of change, in a rate function after an environmental change varies according to the magnitude of the stress, the rate of application of the for the environstress, and whethc,r the organism is a confommcr or a IXmodulator h three phases can be recognized-an mental parameter changed. In general, initial overshoot or undershoot in the rate function, a stabilized rate, and a period of compensation or acclimation. For example, \vhen environmental tcmperatluc is ,suclclcnly raised, most poikilothcrms show an initial rapid overshoot of such rate functions as metabolism; when tc’mpcrature is lowcrcd, they sh0u7 ill1 lmdcrshoot. Overshootin:_: a1~1 Imdcrshooting reactions usually last only a fc\\, mimitcs. Tliesc~ reactions ma\’ bc initiated reHer11~ 1)s- st‘nsory stimulation, ;~lrtl the-ir nia(:nitndc varies with amomlt of tcmpcraturc change; initial ovc’rsltonts and untlcrshoots have bc0i obser\4 also irr ~nicroorjianisms. Similar initial overshoots of metabolism have Beck notclcl in man after sudden heatstrc%ss application. :\ftc,r the initial rrspoiise in intact organisms, or immctliatelv in r~nz\mc~s and isolated tissues, a stable rate is achic~ved. This is th(, rate’ 11sc~l t’ol’ I),,, Inc~aslircill~~nts \I+li tcq~eratin’c. The change in rate ma!’ be consicl~~rcd ah 3 tlircct rqx~~w to mvironmcntal chalrgcl and inay persist for manv lio~irs. If the animal is thc~n rctnnrccl to the original c-nvironmental stat&~.g.. that m-ifinal t~‘mpc,ratnlc--thP rate> returns directly to the 1~~1 prior to thr tlcviation. If the animal is hclcl in the alterc~tl environment for days or u~eks, some c~oml>cnsatory chan~cs occur in rate functions. Thcsc c-olnpcns:~tions rcprment tlict proccsscs of acclimation and if tbcl animal is ~1ow t’cSt71rncd to its ori$$tial ~iivironnrciital condition, its ratr function qocs beyond the original I~cl, thrls indicating that a basic, chanq~ in statr had occlirled tlllring acclimation. T\VO kinds of adaptive acclimation can bc idcntifi(d: capacity and rcsistimce adaptations. The S;~JIW t\vo tx>es of adaptation can be identified gen(,tica]ly. Capacity adaptation, \vhcthcr acclimatory or gcnctic. arcs thosrl permitting rcslativcly normal rates of reaction iIt a mid-raljgc of cnvir(jnmcntal \7ariation, For poikilothcrms, tnv schcrnr-s of capacity adaptations haven been formlllatcd. Prcacht’s classification ( 17 ) for acclimation to louvered tcmpcraturc is as follo\\~s iFi!&. 1): 110 acclimation, i.c.. the rntc remaining at its initial stable levc4 ( tvpc 1); perfect adaptation, i.e., the compcnsuted rat? at the low temperature being thrl samcs ;IS at the highrr tempc’aturc (type 7); partial acclimation with the rate between no and pufect compc~nsation ( type 3) ; overcompensation. i.e., the compensated rate in the cold higher than at thr initial temperature itypc’ 1 ) ; and invcrsc compensation. with tile acclimated rate lower than
C.
LADD
PROSSEH
FIG. 1. Diagram representing patterns of acclimation of a rate function in a poikilotherm to cold. t2, original temperature; tI, lower temperature to which animal is transferred. Patterns: ( 1) overcompensation, (2) perfect compensation, (3) partial compensation, (4) no compensation, ( 5) converse or paradoxic acclimation. ( From Precht ( 17) ) .
the stabilized rate, often explained by complicating secondary environmental factors (type 5). A second classification of rate acclimations is that of Prosser (19) (Fig. 2); this scheme considers not just two points, but the entire curve relating rates and temperature. The acclimated rate curve may be shifted by 1 b Translation
I Patterns of acclimation to cold
c Rotation
e Increased cl 10 /’ /
/
FIG. 2. Patterns of acclimation of rate functions in poikilotherms. Rate functions logarithmically at different temperatures of measurement. W, warm-acclimated C, cold-acclimated animals. (Modified from Prosser and Brown ( 19 ) )
plotted animals;
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translation to the left or right; it may bc rotated with a change in temperature coefficient and with the intersection of the two curves at 10\v, medium, or high temperatures; or the acclimation may consist of a combination of translation and rotation. The pattern of acclimation of enzyme rates may differ according to the enzyme, the tissue in which it is found, and modifying factors. One tissue may show acclimation with respect to cold \;rhen tested iu vitro: another tissur may show no such adaptation. The effect of a given environmental agent, such as cold or heat, may be directly on the cells of the adapting tissues; in other instances it may be mediated by endocrines or by central nervous influences. Acclimation may involve rise of alternate metabolic pathways--for cxampk~, emphasis on the hcxose monophosphate shunt in cold-acclimated fish. 3. Survival limits. ,4t environmental extremes, adaptive variations can he measured in terms of survival of animals, tlevelopmcntal limits, and protein denaturation. Changes in limits of various rate functions with acclimation have been termed “resistance adaptations” by Precht ( 17). The limits of activity of given enzymes may change in the direction of compensation as they usually do in capacity adaptation, or they may not show any relation to capacity adaptation. Thus, the molecular mechanisms of resistance adaptation may be different from those of capacity adaptation. In nature, the distribution of organisms is limited more by environmental extremes than by environmental means. 4. Behavioral adaptations. The first line of defense against environmental stress in animals is usually reflcs. In mamm:lls, the reflexes of piloercction and of vasoconstriction in cold and of sweating. panting, and salivation in heat are well known. Longer-term behavioral acclimations arc sc’cn in nest-building, huddling in cold, in seeking unclerground bllrron-s in heat. I\lany poikilotherms and poikilosmotic animals show “preferred” tcmprraturc~s and salinities. In general, ncrvolls or behavioral adaptations prcscedc metabolic or biochemical ones. \I’e found (20, 21 ) that in fish the temperatures for cold block of spinal reflexcbs. swimming, and conditioned reflcses coultl bc modific~d by acclimation. The time for thcsc’ nervous adaptations is significantly shortcsrthat that for metabolic acclimation (2 days, compared with 10-1-l days, in goldfish). It is l)robablc that muA of the individual variation described in this symposinm reslllts from conditioning of the ner\‘ous system, often at an carlv tl,qe. The ne‘~‘vousmechanisms of adaptation have been studied inadequately.
The molecular bases for the criteria of adaptive variation may be enumerated for both genetically determined and e~lvirolln~eIltal]y induced variations as shommbelow. Primnry Strrrcture of Proteins; Conformationul Chalzges Genetic variations are manifested principally in the structure of proteins synthesized according to the genetic template. Changes in amino acid sequences are strictly fixed by the genotype and cannot be readily altered (except at nonphysiologic extremes). Amino acid squenccs have, in a few instances,
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been correlated with adaptive significance. For example, in fishes and in ccrtain worms, the melting or transition temperature of collagen is clearly cmrelated with the sum of proline and hydrosyproline content ( 12). III thermophilic bacteria, the protein flagcllin is endowed \\,ith heat rcsistancc because of an abundance of amino acids which provide high levels of hydrogen bonding (14).
The translation of rate-temperature curves implies quantitative adaptive changes in enzymes. hleasurcment of turnover of protein by incorporation of radioactive amino acids (e.g., lcllcine ’ ‘C ) shows that, after cold acclimation, fish have cnhanccd synthesis of protein (2). The increased synthesis is found in proteins of various subcellular fractions. Such gcntralizod biochemical change is reasonable in view of the ncccssity for maintained balance in metabolism at different tempcratlucs.
Many proteins aplxar to exist in several forms, each with its own genetic basis. Differc~nces in proportion of specific isozymes in different tissues are known--e.g.. the lactic dehydrogcnases ( LDH’s ) in heart and skeletal muscle. Similarly, in compensatory temperature acclimation. IIochachka (6) has found that, in fish, certain LDII’s arc selectively formed in certain temperaturt ranges. It is probable that selective synthesis of specific forms of given proteins in cliffcrent tissues under the stress of different enviromncntal parameters (direct or indirect via hormones and nervous system) may 1)~ the most general mechaiiism of compensatory acclimation. The adaptive mraning of particular configurations is not yet understood. Such differential synthesis could account for rotational effects on rate-temperature curves.
Lipids It is well established that, in microorganisms as well as in animals, the lipids which are laid down at low temprratures tend to be more unsaturated and have longer chains than those deposited at high temperatlircs. Differences in lipids must rcflcct correlated differences in the enzymes of lipid synthesis. Differences are found in both neutral fats and phospholipids. IIowevcr, the extent to which some enzymatic differences may he explained by differences in lipids of active intracellular membranes is not known. It is probable that some of the adaptations of central nervous systems arc the result of alterations in membrane lipoproteins. Ions and Goe~qmcs Changes in ion balance are known to occur during temperature acclimation in some poikilotherms. TVhether these alterations arc primary or are the result of other adaptive changes is not clear. If is of interest that, even in osmotic conformity, as in some marine molluscs, changes in total osmoconcentration seem to he mediated more by organic molecules than by inorganic ions.
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cdaldished physiology is ;I compl(~ sllhjcd, ant1 principles in relation to homeostatic wntrol orgnnism or wen for one cvtz!‘lIlc~ Hon~evcr, similarities ainollg organisms do Ina!’ Ilot apply to allother systm. cs.\ist allcl man must 1~ consid~wcl as an animal \\ ith cnltllral tnodifications. I%(> scqucqicc of acclimatory modifications in an\’ animal is relatively nnrclatd to the dc~rec of regulation :ind conCornlit)- of internal state. 1. Cewtic alid ciiviroilmei~tally incluccd cliffcrenws among individuals and a~nong “races” cau be distinguished Lvith difficulty. Thcl \vork of IInmmel (5 ) 1 Ecll~olm and Lc\vis (3), \~‘ynclliam ct NI. (27, %I), aucl Adnrns and Covino ( 1 ) indicates racial diffrrc~ncc~s in wspcct to trmpcrature regrllation. Thcl Rants at the same clc~vuted tcxnprraturr; a\-cat rate, is 1~~s than tlrat of Europcal~s the critical ambient tcmperat1ire for iiicrcxsing metal~olic heat production is Jo\\Y~J.for Negroc5 thall for Cnncasifi~~s; the Alxxigincs at night on the Xustralinn clcscrt tolerate a rduccd body tcwqxutuw, while Norwegians acclimated to colt1 ambient temperature had higher metabolism thalt ~:hen not acdimnted. I<\-amplc5 of c~iivironmel~tnll~ inclucc~tl variations arc mow familiar. In heat acclimation, the skin tc~mpwxturr for iilitiating of s\\rcating is rtduccd. \‘xomotor conditioning mtl rctlucocl srnsiti\,ity of skin rccc~ptors OCL’III‘ in the hancls of fishcrmcii ~vorliing \vitli cold nets (3). A scaric5 of adaptive cliaiqys occm in pwsons living at high ~iltitnclrs. In attempts to undcrstancl inclividi~al \wiatious, tlicx distinction lx+\\.een ontogeiic+c (d(~\~~~lol~~~ieiital) ant1 adults c011clitioning ncwls to lx c~ramind in grc>atrr clt+ail. 2. The sequence of adaptive responses to c~nvironmcntal variation may 1~ similar in mammals to that in lo\vcr animals, even though the manifestations aw diffcrcnt. The grncral scquenw of initial responses and late acclimation to cold in mammals is: pilomotor and v;isomotor rdbxs, which provitl(. insulation; lwhnvioral reactions, which are protective; shivering as a iiieans of lwat prodilction: nonshiverin~ tlirrll~oji~,lc‘sis, or hcnt production lnrgdy from now miiscrilar tissues; long-turn insulative changes, sucl~ as increased coat of hair; dcucwccl sensitirity of skin receptors in soifw spccic5; and elc771te~l rnctahlic rate,. Thus, in both homcotlwrms rind poikilotherms, oxygen consumption increnscs d’tm prolorqgcd cooling. In poikilothernrs, the net d&t of compensatory acclimation of metabolic enzymes is to maintain relatively constant energy output at clifferc>nt temperatures (Fig. 3). IIomeotherms sho\v c~nhanced metal~olism in thca cold after they reach the stage of llonshivering thcrmogctnesis; the net t&cd is to maintain constant body temperature with cliffercwt energy outputs ( Fig. 4). In poikilotherms ancl homeotherms. thr enzymatic changes show ~~ilvirorn~l~ntal
for ow
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POIKILOTHERM I
Internal Temperature
AMBIENT
TEMPERATURE
FIG. 3. Diagram of metabolism and body temperature pensates metabolically by acclimation to different ambient ture is same as ambient, initial metabolism shows high shows compensation at low (T,) and high (T?) temperature.
of a poikilotherm which comptemperatures. Internal temperaQlo, acclimated final metabolism
striking resemblances in metabolic compensations for cold, even though the purpose is different. Compensation in the direction of reduced metabolism occurs in acclimation to heat in both poikilotherms and homeotherms. For example, laboratory rats show marked increase in 0, consumption when transferred from ambient temperature of 28°C to 34”C, but after 2-4 days, their oxygen consumption returns to near its original value ( 11) . 3. Acclimation of metabolism. The time after ruposurc~ to a given stressful environment and the rate of environmental change strongly influence the adaptive variations which are observed. An esamplc is the metabolic compensation of homeothcrms to prolonged cooling. For acute measurements of metabolism at different ambient temperatures, a thermoneutral zone is observed over which
I
Body Temperalure
Metabolism
AMBIENT
TEMPERATURE
FIG. 4. Diagram of metabolism and body temperature of a homeotherm which maintains constant body temperature at different ambient temperatures. Metabolism is minimal over thermoneutral zone when insulative reactions adequately maintain body temperature. At lower temperatures, metabolism increases initially after acclimation ( final), the critical temperature for metabolism increase may be lower and the rate of increase of metabolism per degree of lowering of ambient temperature may decrease. The slopes of metabolism-temperature curves may extrapolate to body temperature.
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insulative responses arc adequate to maintain constant body temperature. This thermoneutral zone may be broad, as in well-furred or feathered large animals, or it may be narrow, as in poorly insulated and small animals. At the critical low temperature, insulati\,e mechanisms fail and heat production increases. Scholander et al. (23) found, and it has been frequently confirmed, that for moderate-sized mammals and birds the metabolism rises with reduced ambient temperatures according to Newton’s law of cooling and that the metabolismtemperature curve tends to extrapolate to body temperature (Fig. 4). The critical temperature varies with degree of insulation, and the slope of the metabolism-ambient temperature curve may be modified by heat distribution in the animal tissues. If, on the contrary, the observations are made chronically-that is, on animals acclimated to the temperatures at which measurements arc made-very difberent results are obtained. For cuample, in grosbeaks the slope of the acclimated metabolism-temperature curve extrapolates not to 38”C, but to about 50°C. Also, the :lcclimated metabolism varies according to whether the cooling Is cyclic or constant (25). Similarly, in cattle shifted from 63°F to 110°F over 6 hr the 0, consumption rose abruptly as heat regulation was established, whereas when similar cattle were subjected gradually over a 5-month period to a comparable elevation of environmental temperature (from 53°F to 95”F), their metabolism actually decreased ( 13). The metabolism-ambient temperature curve for white-throated sparrows estrapolatcd to body temperature at night when insulation was good, but e.\-trapolated to higher temperatures by day, when birds were active (7). In man, the metabolism-temperature curve varies greatly according to the conditions of measurement and time for equilibration. Acutelv mcasurcd curves may be curvilinear and mny extrapolate to about 25’C or slightly higher. This must be related to heat transfer between body core and periphery. Also, the curves in man are much steeper when evaporative stress is high than in still air, and the curves in csercise are diffcrcnt from those obtained at rest. Measurements made in men, naked but escrcising by bicycle to achieve comfort, extrapolate to 37°C (22). True acclimated curves have not been constructed at many temperatures for man. and present evidence fails to explain the marked difference between metabolism-ambient temperature curves for man and furred mammals.
I>espitc the similarities among animals mentioned above, man shows so many diffcrenccs from other animals that extrapolation is diffkuk. Some of the biologic characteristics which are prominent in man are the following: I. Man constitutes one biologic species. There is no reproductive isolation among populations or races. except that which may be socially imposed. It is most unlikely that modern man can ever evolve into subspecies, This means that genetically al1 men arc reproductively compatible. No other such cosmopolitan species exists. 2. Man shows remarkable phenotypic liability. Human populations are adapted
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to a wide range of climates-dry and moist air, cold and hot climates, reduced oxygen at high altitudes. This phenotypic lability permits many environmentally induced adaptations; the genetic limits for these arc extremely wide for man. As pointed out by Ernst Mayr (16), such phenotypic flexibility retards evolution and permits extension of range nongenetically. 3. Most of the adaptive characters of man are based on multiple alleles; these have been well analyzed for such proteins as hemoglobin (9). At the same time, pleiotropism is extreme; single cistrons lead to multiple effects. This is shown by correlated characters-for example, the relation between blood groups and certain types of carcinoma. 4. In human populations, balanced polymorphism is important. Individuals show great genetic diversity and in a population no two individuals (except for identical twins) are genetically identical. This means that certain recessive characters are bomld to be maintained at a fixed ratio under steady-stat<, conditions (as specified by the Hardy-V’einbcrg law), and the probability of eliminating such characters is virtually zero. Balanced polymorphism has been observed to impart certain advantages to populations, \vhcther in nature or in breeding cages (4). First, it means that for most characters there is a prcldominance of heteroxygotcs with the resulting biologic advantages of heterosis. At the same time, some characters are carried in cryptic form. Heterozygotcs tend to be more vigorous than homozygotes in general and to sho\v greatrr success in variable and stressful environments, whereas homozygotcs tend to he more influenced by the environment and heterozygotcs more resistant. Manced polymorphism can account for the maintained percentages of vnriolls characters in different populations. For csamplc, most individuals homozygous for sickle-cell anemia die before the age of 5 years, yet hetc~rozygotes are maintained at 40% in central Africa, 30% in India, and 17% in Greccc. The correlation of heterozygosity for sickle-cell anemia with resistance to malaria is well kno\vn. Similarly, blood types are maintained in balanced proportions in populations. 5. Man has evolved culturally very rapidly, biologically very slowly. Cnltural transmission provides for a wealth of adaptive traits. most of them bein housing and clothinghavioral. CulturalIy acquired traits-for example, permit survival in a midc range of climates. As a result, the microclimatc~ in which man lives is remarkably uniform; an Eskimo in his furs lives at a microclimatic tempcraturc similar to that of an Indian in the tropics. Cultural inhcritance and cultural evolution are much less important in the adaptation of animals to cnviromnents, although nongcnetically acquired behavior does kst. In conclusion. it must be emphasized that the patterns and molecular mcchanisms of both genetic and nongenetic adaptive variation in animals are worthy of study in their own right. This is part of our continuing effort to understand life processes, irrespective of direct application to man. The interactions between organisms and their environments are exceedingly compkx, and no single limiting mechanism exists for one c,nvironmentaI parameter in a given species. The time course of acclimation and the different effects of varied rates of change of an environmental parameter must be carefully examined for all adaptive responses. There is need for much research on the mechanism of
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adaptive variation--studies at all levels of biologic organization. Extrapolation from animals to man must be viewed with extreme caution because of man’s biologic uniqueness. HEFEREXCES 1. :\DAMs, T., XXI) CO~INO, B. (:. ( 1948). Racial variations to a standardized cold strew J. Appt. Physiot. 12, 9-12. 2. DAS, A.. AND PROSSER, C. L. ( 1967). Biochemical changes in goldfish acclimated to II. Protein synthesis. Camp, Biochcm. Physiol. 21, 449367. high and low trmperatures. :3. &)HoLBI, 0. C., AND LEWIS, H. S. (19613). Terrestrial animals in cold: man in polar Sect. 4. Am. Physiol. Sot. Washington, D. C. pp. regions, III “Hantlhook of Physiology.” 4.35-436. “Genetic Polylllol-phism.” M.I.T. Press, Cambridge, Massachusetts. 4. FORD, E. B. ( 1965). Terrestrial animals in cold: recent stuclies of primitive man. 5. ~IAAlAiEL, I-1. T. (196.3). Sect, 4, pp. 113-43-f. Am. Physiol. Sot., Washington, D.C. Zn “Hantll~ook of Physiology,” 6. l~Oc:r~~c:~~a, P. W. ( 1966 ) Lactate dehydrogenases in poikilotherms: Definition of c~ complrs enzyme system. Corn)>. Biocl2. Ph!pio/. 18, 261-270. ;. fIUl,SON, J. \%'.. ASI) krlhlZEY, S. I,. ( 1966). Temprrictnre rcpulation and mrtaholic Pnsser dnn2mticlts. Camp. Binrhcm. rhythms in populations of the house sparrow, Plnysinl. 17, 203-217. N. IAMPIETRO, P. F., VAUGHAS, J, A., COLINAN, H. F., KREIDEH, 51. B., hlxx~cxr, I?., ANI) Bass, D. E. ( 1960). IIeat production from shivering. J. A~~JII. Physiol. 15, 632-634. 9, IXGRAHAAI, V. 1%. ( 1963). “The Hemoglobins in Cknetics and Evolution.” Colnmlk~ ITniv. Press, Sew York to. ]ASSKY, mechanisms in homeotherms. I,. ( 1965). Adaptability of heat production .4cto Unir. caroh2uc~ Biozo~:icu, I-9 1. course of oxygen consumption in rats during sllddcw II. JOIISSOS, II. ( 1967 ). Time e\powre to high mvironmental temperature. Li,k Sci. 6, 1221-1228. 12. ~osw., J., Ah'11 HA~wISGT~N, W. F. ( 1964 ). Role of pyrrolitline residnc~s in structure and stabilization of collagen. J. hfolec. Bid. 9, 269-287. 13. KIULEH, H. H. ( 1962). oxygen consumption in cattle in relation to rate of increaw in environmental temperatwe. Nntrrre 186, 972-973. 1.1. Eomt~n, H., I\IALLETT. (:. E., AND ADYE, J. ( 1957 ) Slolecular basis of l~iological stability to high trmperaturc. Proc. h’atl. Acud. Sci. 43, l64--177. 15. LADELL, W. S. S. (1963). Terrestrial animals in humid heat: man, pp. 62%660. In “Handlx~ok of Physiology,” Sect. 4, Am. Phy.riol. Sot., Washington, D. C. IG. ~IAY~, E. ( 196.3). “Animal Speciation and Evolution.” Harvard I!niv. Prrss, Cambridge, Massachasctts. 17. PRECHT, H. ( 195X). Concepts of temperature adaptation of unchanging reaction systems of coltl-l)looded animals. 111 “Physiological Adaptation.” ( C. L. Presser, etl. ) pp. 50-78. Am. Ph!~siol. Sot., Washington, D. C. 18. PROSSER, C. L. (1963). Perspectives of adaptation: theoretical aspects. In “Handbook of Physiology.” Sect. 4, pp. 11-25. Am. Physiol. Sot., Washington, D. C. 19. I’nosse~, C. L., AUU BRO\VV, F. A. ( 1961). “Comparativr Animal Physiology.” Sanndcrs, Philadelphia, Pennsylvania. 20. ~‘IKS~EH, C. L., .+.Ku FAHHI, E. ( 1965). Effects of temperature on conditioned reflexes and on nerve contlllction in fish. Z&w11. ocql. Phgsiol. 50, 91-101. 21. Ho0.1.s. B. J., AND PIVXSER. C. I,. ( 1962 ). Tcwlperatnre acclimation and the nervous s)~strm in fish. J. &q~f2. Viol. 39, 617-629. 22. S(:HOLANDER. P. I?.. AWERSOS, K. L., Kaoc. J., LOIIENTZE:N, F. V., ASL) STEEN, J. (1957). Critical temprratnre in I,apps. J. AJ,J,I. Ph!pio/. 10, 231-234. 2.3. SCHOLANIXR, I'. F., WALTERS, \'., Hots, R., AND IRVING, L. ( 1960). Body insnlation (If SI)IIW arctic d tropical nx~mnds ;und bir&s. Riol. Bull. 99, 225-236.
416 24. 25. 26. 27.
28. 29.
C.
LADD
PROSSER
THOMPSON, G. R. (1962). Significance of haemoglobins S and C in Ghana. Brit. Med. J. 1, 682-685. WEST, G. C., AND HART, J. S. ( 1966). Metabolic responses of evening grosbeaks to constant and to fluctuating temperatures. Physid. Zool. 39, 171-184. WYNDHAM, C. H. ( 1965). Adaptation of some of the different ethnic groups in southern Africa to heat, cold and esercise. So& Africun J. Sci. 61, 11-29. WYNDHAA~, C. Ii., MORKISON, J. F., WARD, J. S. BREDELL, C. A. G., VAN RAHDEN, Al. E., HOLDSWORTH, L. D., WENZEL, H. G., AND MUNRO, A. ( 1964 ). Physiological reactions to cold of Bushmen, Bantu and Caucasian males. J. Appl. Ph!/siol. 19, 868476. WYNDHA~I, C. H., PLOTKIN, R., AND MUNRO, A. ( 1964 ). Physiological reactions to cold of men in Antarctic. J. Appl. Pht~siol. 19, 593-597. WYNDHA~~, C. H., WARD, J. S., STRYDO~~, N. B., MONUSON, J. F., WILLIA~IS, C. G., BREDELL, C. A. G., PETER, J., YAR’ RAHDEN, M. J. E., HOLDSWORTH, L. D., VAN GRAAN. c. II., VAN RENS!,UK, A. J., AND hfUNR0, A. ( 1964). Physiological reactions of Caucasian and Bantu IX&S in acute eaposure to cold. J. Appl. Phgsioi. 19, 583-592.
RESEARCH
Principles
2, 304416
and
( l%?))
General
Concepts
of
Adaptation1
C. LADD PROSSER
My assignment in this conference is to present some of the principles of physiological adaptation from the viewpoint of a general biologist. First, I wish to present some definitions in the hope that this conference may agree on a common terminology. It is unfortunate that in many standard works; for example, the Handbook of Physiology (3, 5, 15, IS), certain words are used by different contributors with very different meanings. I hope to show that the general terminology developed by comparative physiologists is applicable to human physiology. Further, while most of my examples will be drawn from temperature stresses,the terminology is equally applicable to such other environmental parameters as hypoxia. osmotic and ionic stresses, and nutritional factors. The word “adaptation” has many meanings and should be defined in each context in which it is used. If I were to ask 100 biologists for the meaning of adaptation, I might get 100 different definitions. It may well be that this word is no longer precise enough for serious usage. For some, adaptation refers to those properties (usually anatomic) which have been selected over long periods of evolution to permit survival. For others, adaptation refers to the rapid decay of an excitatory process, as in srnsory adaptation, For still others, adaptation refers to any ltomeostatic reaction, In the present discussion, adaptation refers to any property of an organism which permits physiological activity and survival in a specific environment; adaptation is characteristically related to stressful components of the environment although it may relate equally well to a total environment. Adaptive characters have clrrrrtic basis but may be expressed according to environmental needs. A response is a direct reaction, either adaptive or nonadaptive to an cnvironmental stimulus, It is usually, but not necessarily, reversiblr. An example would be a direct change in rate of a chemical reaction with temperature, as in a Ql,, effect. Adaptive variations may be measured in individuals. populations, or higher taxonomic categories. They include anatomic. physiologic, and biochemical characteristics of individual organisms which relate thcsc, individuals adaptively to a specific environment. In an evolutionary sense, only those v,ariations that arc adaptive are retained. Natural selection is the only known mrchanism for fix:rtion of adaptive variations and forms the basis for speciation.
PHINCIPLES
AND
CONCEPTS
OF
ADAPTATION
405
,\ physiological concept of biological species may be derived as follows: If no two species can occupy the same ecological niche or the same geographic range throughout their life cycles, it follows that every species must be uniquely adapted to its particular niche and range. Hence, if we could quantitatively describe the physioIogica1 adaptedness of a species to its ecological niche and geographic range, we would have a truly meaningful description of the species. One of the goals of environmental physiology is to achieve some understanding of the molecular basis for natural sckbction. However in the contest of this conference adaptive variations are considered for individuals, not sp(bc:ies. “Homeostasis“ is a term which has been broadened from the original meaning of Cannon to refer to self-stabilizin g states or organisms, societies, and computers. Physiologically. vv;c’ can use “homc~ostasis” not only for maintenance of constancy of the internal c~nvironmcnt, biit also for maintenance of constancy of energctics, of work capacity, of self-identity, and of independence of the external environment. The (pence of living things is to be at once apart from their environment rind a part of the environment. Homeostnsis describes the sum total of propertic’s contributing to the “apartness” of inclividuals.
The goals of cnv-ironmcntal physiolog! ma!~ be listed sequentially in three categoric3 : .l. To describe adaptive variations in or ganisms-whether individuals, populations, races, or species. Much remains to be done in this dcscriptivc phase with respect to human adaptive variation. It is not always easy to identify how a given character is adaptive-for example, pigmented skin in Negroes. Biologic meaning of some characters may he found onh in genetic linkage and plciotropism, as in sickle-cell anemia. 2. To discover the origin of such variations as are described-whether genetic or cnvironmcntally induced. Genetically determined variation is based on selection from random variation and is transmitted in the genotype. Environmentally induced, or nongenetic, variations may bc transitory for individuals or may be transmitted culturally from generation to generation. Genetically determined variation can generally he distinguished from nongenetic by acclimation or acclimatization supplemented by breeding experimcnts. Acclimation consists of those conpensatory changes which occur in intlividuaIs mlder controlled laborator)- conditions whcrc only one environmental parameter is varied, for example temperature or photoperiod. Acclimatization consists of those adaptive changes which occur under natural conditions when multiple factors vary, as in diffcrcut climates, seasons, and geographic conditions. For csample. the changes occurring in a rodent out-of-doors in the winter differ from the changes in similar animals in a cold room. Identification of critical environmental strcssors is not ahvnys clear when th(y ar(x multipletemperahue, photoperiod. nutrition. and others. Acclimation in man is difficult to obtain. although acclimatization has been milch studied. Prolonged czposures in d~~comprc~ssion chambers have provided
406
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PROSSER
a basis for comparing acclimation to low pressure with acclimatization in high mountains. Acclimation to heat or cold has been studied with periodic, repetitive, or l-week exposures in temperature chambers, but how this differs from continuous exposure for long times at a constant temperature is not established. Life in the Arctic or Antarctic is very different from that in a cold room. Evidence is now accumulating that animals from very mliform environments may lose their capacity for acclimation while those which live in highly variable environments have maximal capacity for acclimation. This has practical importance for the adaptability of transplanted populations and species. The genotype sets the limits within which environmentally induced variation can occur, that is, the range of phenotypic variability. A major task in human biology is to separate the two causes of variation-genetic and environmentally induced. 3. To explain adaptive variation at all levels of organization. This includes a description of feedback interaction between environment and organism-for example, the regulation of synthesis of specific proteins by environmental stressors. Explanation of variation in biochemical terms may elucidate the molecular basis for natural selection. CRITli,RI.A
OF
PHYSIOLOGIC
VAKIATION
Criteria of physiologic variation may bc grouped into four broad categories ( 18). 1. Internal state for a given parameter as a function of that parameter in the environment. This is the essence of homeostasis and may occur in either of two patterns or a mixture of these: Conformity of internal state to the environmentul stute. Familiar examples are poikilothermic and poikilosmotic animals in which temperature or osmotic concentration in body fluids and tissues rises and falls with these parameters in the external environment. Conformity is homeostatic in its broader meaning, in that enzyme systems of conformers can function over a wide range of internal environments. In man and other naked mammals, and in aquatic mammals, the skin temperature can vary widely according to cnvironmcntal temperature, and enzymes of skin may be adapted to be active over a much wider temperature range than corresponding enzymes of liver. Regulation or constclnuy of intetnal stnte. As the environmental parameter changes, feedback control reactions tend to maintain internal constancy; at some limitinq c gradient, these control reactions fail and the internal state changes abruptly. Familiar examples are maintenance of constant body temperature, constant blood sugar, and constant sodium-potassium ratios in body fluids. The cost of adaptation by internal regulation is considerable, but internal constancy permits body functions over a wide environmental variation. In general, conformers tolerate wider internal variation, and regulators, wider external variation, with respect to a given parameter. Many animals show combinations of the two patterns, regulation of one parameter or in one environmental range and conformity in another, or regulation at one stage
PHINCIPLES
AND
CONCEPTS
OF
ADAPTATIOK
-m
in development or time in a life cycle. A hibernating mammal is a tempcraturc conformer over a certain range when torpid, a regulator to relatively internal temperature when active. A related measure of variation is the rate of recovery of internal state after For example, the pattern of recover). drviation due to a stressing espcricnce. of normal water load after dehydration is specific to a species. 3. Rat(- functions. Any biologic function that can bc measured as ~1 rate of adaptive variation when with respect to time may br used as ;I criterion tested in different environmental states. ~hc time course of change, in a rate function after an environmental change varies according to the magnitude of the stress, the rate of application of the for the environstress, and whethc,r the organism is a confommcr or a IXmodulator h three phases can be recognized-an mental parameter changed. In general, initial overshoot or undershoot in the rate function, a stabilized rate, and a period of compensation or acclimation. For example, \vhen environmental tcmperatluc is ,suclclcnly raised, most poikilothcrms show an initial rapid overshoot of such rate functions as metabolism; when tc’mpcrature is lowcrcd, they sh0u7 ill1 lmdcrshoot. Overshootin:_: a1~1 Imdcrshooting reactions usually last only a fc\\, mimitcs. Tliesc~ reactions ma\’ bc initiated reHer11~ 1)s- st‘nsory stimulation, ;~lrtl the-ir nia(:nitndc varies with amomlt of tcmpcraturc change; initial ovc’rsltonts and untlcrshoots have bc0i obser\4 also irr ~nicroorjianisms. Similar initial overshoots of metabolism have Beck notclcl in man after sudden heatstrc%ss application. :\ftc,r the initial rrspoiise in intact organisms, or immctliatelv in r~nz\mc~s and isolated tissues, a stable rate is achic~ved. This is th(, rate’ 11sc~l t’ol’ I),,, Inc~aslircill~~nts \I+li tcq~eratin’c. The change in rate ma!’ be consicl~~rcd ah 3 tlircct rqx~~w to mvironmcntal chalrgcl and inay persist for manv lio~irs. If the animal is thc~n rctnnrccl to the original c-nvironmental stat&~.g.. that m-ifinal t~‘mpc,ratnlc--thP rate> returns directly to the 1~~1 prior to thr tlcviation. If the animal is hclcl in the alterc~tl environment for days or u~eks, some c~oml>cnsatory chan~cs occur in rate functions. Thcsc c-olnpcns:~tions rcprment tlict proccsscs of acclimation and if tbcl animal is ~1ow t’cSt71rncd to its ori$$tial ~iivironnrciital condition, its ratr function qocs beyond the original I~cl, thrls indicating that a basic, chanq~ in statr had occlirled tlllring acclimation. T\VO kinds of adaptive acclimation can bc idcntifi(d: capacity and rcsistimce adaptations. The S;~JIW t\vo tx>es of adaptation can be identified gen(,tica]ly. Capacity adaptation, \vhcthcr acclimatory or gcnctic. arcs thosrl permitting rcslativcly normal rates of reaction iIt a mid-raljgc of cnvir(jnmcntal \7ariation, For poikilothcrms, tnv schcrnr-s of capacity adaptations haven been formlllatcd. Prcacht’s classification ( 17 ) for acclimation to louvered tcmpcraturc is as follo\\~s iFi!&. 1): 110 acclimation, i.c.. the rntc remaining at its initial stable levc4 ( tvpc 1); perfect adaptation, i.e., the compcnsuted rat? at the low temperature being thrl samcs ;IS at the highrr tempc’aturc (type 7); partial acclimation with the rate between no and pufect compc~nsation ( type 3) ; overcompensation. i.e., the compensated rate in the cold higher than at thr initial temperature itypc’ 1 ) ; and invcrsc compensation. with tile acclimated rate lower than
C.
LADD
PROSSEH
FIG. 1. Diagram representing patterns of acclimation of a rate function in a poikilotherm to cold. t2, original temperature; tI, lower temperature to which animal is transferred. Patterns: ( 1) overcompensation, (2) perfect compensation, (3) partial compensation, (4) no compensation, ( 5) converse or paradoxic acclimation. ( From Precht ( 17) ) .
the stabilized rate, often explained by complicating secondary environmental factors (type 5). A second classification of rate acclimations is that of Prosser (19) (Fig. 2); this scheme considers not just two points, but the entire curve relating rates and temperature. The acclimated rate curve may be shifted by 1 b Translation
I Patterns of acclimation to cold
c Rotation
e Increased cl 10 /’ /
/
FIG. 2. Patterns of acclimation of rate functions in poikilotherms. Rate functions logarithmically at different temperatures of measurement. W, warm-acclimated C, cold-acclimated animals. (Modified from Prosser and Brown ( 19 ) )
plotted animals;
IWNCIPLES
AND
COSCEPTS
OF
ADAPTATION
309
translation to the left or right; it may bc rotated with a change in temperature coefficient and with the intersection of the two curves at 10\v, medium, or high temperatures; or the acclimation may consist of a combination of translation and rotation. The pattern of acclimation of enzyme rates may differ according to the enzyme, the tissue in which it is found, and modifying factors. One tissue may show acclimation with respect to cold \;rhen tested iu vitro: another tissur may show no such adaptation. The effect of a given environmental agent, such as cold or heat, may be directly on the cells of the adapting tissues; in other instances it may be mediated by endocrines or by central nervous influences. Acclimation may involve rise of alternate metabolic pathways--for cxampk~, emphasis on the hcxose monophosphate shunt in cold-acclimated fish. 3. Survival limits. ,4t environmental extremes, adaptive variations can he measured in terms of survival of animals, tlevelopmcntal limits, and protein denaturation. Changes in limits of various rate functions with acclimation have been termed “resistance adaptations” by Precht ( 17). The limits of activity of given enzymes may change in the direction of compensation as they usually do in capacity adaptation, or they may not show any relation to capacity adaptation. Thus, the molecular mechanisms of resistance adaptation may be different from those of capacity adaptation. In nature, the distribution of organisms is limited more by environmental extremes than by environmental means. 4. Behavioral adaptations. The first line of defense against environmental stress in animals is usually reflcs. In mamm:lls, the reflexes of piloercction and of vasoconstriction in cold and of sweating. panting, and salivation in heat are well known. Longer-term behavioral acclimations arc sc’cn in nest-building, huddling in cold, in seeking unclerground bllrron-s in heat. I\lany poikilotherms and poikilosmotic animals show “preferred” tcmprraturc~s and salinities. In general, ncrvolls or behavioral adaptations prcscedc metabolic or biochemical ones. \I’e found (20, 21 ) that in fish the temperatures for cold block of spinal reflexcbs. swimming, and conditioned reflcses coultl bc modific~d by acclimation. The time for thcsc’ nervous adaptations is significantly shortcsrthat that for metabolic acclimation (2 days, compared with 10-1-l days, in goldfish). It is l)robablc that muA of the individual variation described in this symposinm reslllts from conditioning of the ner\‘ous system, often at an carlv tl,qe. The ne‘~‘vousmechanisms of adaptation have been studied inadequately.
The molecular bases for the criteria of adaptive variation may be enumerated for both genetically determined and e~lvirolln~eIltal]y induced variations as shommbelow. Primnry Strrrcture of Proteins; Conformationul Chalzges Genetic variations are manifested principally in the structure of proteins synthesized according to the genetic template. Changes in amino acid sequences are strictly fixed by the genotype and cannot be readily altered (except at nonphysiologic extremes). Amino acid squenccs have, in a few instances,
410
C.
LADD
PROSSER
been correlated with adaptive significance. For example, in fishes and in ccrtain worms, the melting or transition temperature of collagen is clearly cmrelated with the sum of proline and hydrosyproline content ( 12). III thermophilic bacteria, the protein flagcllin is endowed \\,ith heat rcsistancc because of an abundance of amino acids which provide high levels of hydrogen bonding (14).
The translation of rate-temperature curves implies quantitative adaptive changes in enzymes. hleasurcment of turnover of protein by incorporation of radioactive amino acids (e.g., lcllcine ’ ‘C ) shows that, after cold acclimation, fish have cnhanccd synthesis of protein (2). The increased synthesis is found in proteins of various subcellular fractions. Such gcntralizod biochemical change is reasonable in view of the ncccssity for maintained balance in metabolism at different tempcratlucs.
Many proteins aplxar to exist in several forms, each with its own genetic basis. Differc~nces in proportion of specific isozymes in different tissues are known--e.g.. the lactic dehydrogcnases ( LDH’s ) in heart and skeletal muscle. Similarly, in compensatory temperature acclimation. IIochachka (6) has found that, in fish, certain LDII’s arc selectively formed in certain temperaturt ranges. It is probable that selective synthesis of specific forms of given proteins in cliffcrent tissues under the stress of different enviromncntal parameters (direct or indirect via hormones and nervous system) may 1)~ the most general mechaiiism of compensatory acclimation. The adaptive mraning of particular configurations is not yet understood. Such differential synthesis could account for rotational effects on rate-temperature curves.
Lipids It is well established that, in microorganisms as well as in animals, the lipids which are laid down at low temprratures tend to be more unsaturated and have longer chains than those deposited at high temperatlircs. Differences in lipids must rcflcct correlated differences in the enzymes of lipid synthesis. Differences are found in both neutral fats and phospholipids. IIowevcr, the extent to which some enzymatic differences may he explained by differences in lipids of active intracellular membranes is not known. It is probable that some of the adaptations of central nervous systems arc the result of alterations in membrane lipoproteins. Ions and Goe~qmcs Changes in ion balance are known to occur during temperature acclimation in some poikilotherms. TVhether these alterations arc primary or are the result of other adaptive changes is not clear. If is of interest that, even in osmotic conformity, as in some marine molluscs, changes in total osmoconcentration seem to he mediated more by organic molecules than by inorganic ions.
.-\I’I’LIC:.A’I’ION
01;
‘fllk:
l’KIY(:Il’I,ES
7‘0
11.41
cdaldished physiology is ;I compl(~ sllhjcd, ant1 principles in relation to homeostatic wntrol orgnnism or wen for one cvtz!‘lIlc~ Hon~evcr, similarities ainollg organisms do Ina!’ Ilot apply to allother systm. cs.\ist allcl man must 1~ consid~wcl as an animal \\ ith cnltllral tnodifications. I%(> scqucqicc of acclimatory modifications in an\’ animal is relatively nnrclatd to the dc~rec of regulation :ind conCornlit)- of internal state. 1. Cewtic alid ciiviroilmei~tally incluccd cliffcrenws among individuals and a~nong “races” cau be distinguished Lvith difficulty. Thcl \vork of IInmmel (5 ) 1 Ecll~olm and Lc\vis (3), \~‘ynclliam ct NI. (27, %I), aucl Adnrns and Covino ( 1 ) indicates racial diffrrc~ncc~s in wspcct to trmpcrature regrllation. Thcl Rants at the same clc~vuted tcxnprraturr; a\-cat rate, is 1~~s than tlrat of Europcal~s the critical ambient tcmperat1ire for iiicrcxsing metal~olic heat production is Jo\\Y~J.for Negroc5 thall for Cnncasifi~~s; the Alxxigincs at night on the Xustralinn clcscrt tolerate a rduccd body tcwqxutuw, while Norwegians acclimated to colt1 ambient temperature had higher metabolism thalt ~:hen not acdimnted. I<\-amplc5 of c~iivironmel~tnll~ inclucc~tl variations arc mow familiar. In heat acclimation, the skin tc~mpwxturr for iilitiating of s\\rcating is rtduccd. \‘xomotor conditioning mtl rctlucocl srnsiti\,ity of skin rccc~ptors OCL’III‘ in the hancls of fishcrmcii ~vorliing \vitli cold nets (3). A scaric5 of adaptive cliaiqys occm in pwsons living at high ~iltitnclrs. In attempts to undcrstancl inclividi~al \wiatious, tlicx distinction lx+\\.een ontogeiic+c (d(~\~~~lol~~~ieiital) ant1 adults c011clitioning ncwls to lx c~ramind in grc>atrr clt+ail. 2. The sequence of adaptive responses to c~nvironmcntal variation may 1~ similar in mammals to that in lo\vcr animals, even though the manifestations aw diffcrcnt. The grncral scquenw of initial responses and late acclimation to cold in mammals is: pilomotor and v;isomotor rdbxs, which provitl(. insulation; lwhnvioral reactions, which are protective; shivering as a iiieans of lwat prodilction: nonshiverin~ tlirrll~oji~,lc‘sis, or hcnt production lnrgdy from now miiscrilar tissues; long-turn insulative changes, sucl~ as increased coat of hair; dcucwccl sensitirity of skin receptors in soifw spccic5; and elc771te~l rnctahlic rate,. Thus, in both homcotlwrms rind poikilotherms, oxygen consumption increnscs d’tm prolorqgcd cooling. In poikilothernrs, the net d&t of compensatory acclimation of metabolic enzymes is to maintain relatively constant energy output at clifferc>nt temperatures (Fig. 3). IIomeotherms sho\v c~nhanced metal~olism in thca cold after they reach the stage of llonshivering thcrmogctnesis; the net t&cd is to maintain constant body temperature with cliffercwt energy outputs ( Fig. 4). In poikilotherms ancl homeotherms. thr enzymatic changes show ~~ilvirorn~l~ntal
for ow
412
C.
LADD
PROSSER
POIKILOTHERM I
Internal Temperature
AMBIENT
TEMPERATURE
FIG. 3. Diagram of metabolism and body temperature pensates metabolically by acclimation to different ambient ture is same as ambient, initial metabolism shows high shows compensation at low (T,) and high (T?) temperature.
of a poikilotherm which comptemperatures. Internal temperaQlo, acclimated final metabolism
striking resemblances in metabolic compensations for cold, even though the purpose is different. Compensation in the direction of reduced metabolism occurs in acclimation to heat in both poikilotherms and homeotherms. For example, laboratory rats show marked increase in 0, consumption when transferred from ambient temperature of 28°C to 34”C, but after 2-4 days, their oxygen consumption returns to near its original value ( 11) . 3. Acclimation of metabolism. The time after ruposurc~ to a given stressful environment and the rate of environmental change strongly influence the adaptive variations which are observed. An esamplc is the metabolic compensation of homeothcrms to prolonged cooling. For acute measurements of metabolism at different ambient temperatures, a thermoneutral zone is observed over which
I
Body Temperalure
Metabolism
AMBIENT
TEMPERATURE
FIG. 4. Diagram of metabolism and body temperature of a homeotherm which maintains constant body temperature at different ambient temperatures. Metabolism is minimal over thermoneutral zone when insulative reactions adequately maintain body temperature. At lower temperatures, metabolism increases initially after acclimation ( final), the critical temperature for metabolism increase may be lower and the rate of increase of metabolism per degree of lowering of ambient temperature may decrease. The slopes of metabolism-temperature curves may extrapolate to body temperature.
I’RISClPl,ES
AND
COKCEPTS
OF
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insulative responses arc adequate to maintain constant body temperature. This thermoneutral zone may be broad, as in well-furred or feathered large animals, or it may be narrow, as in poorly insulated and small animals. At the critical low temperature, insulati\,e mechanisms fail and heat production increases. Scholander et al. (23) found, and it has been frequently confirmed, that for moderate-sized mammals and birds the metabolism rises with reduced ambient temperatures according to Newton’s law of cooling and that the metabolismtemperature curve tends to extrapolate to body temperature (Fig. 4). The critical temperature varies with degree of insulation, and the slope of the metabolism-ambient temperature curve may be modified by heat distribution in the animal tissues. If, on the contrary, the observations are made chronically-that is, on animals acclimated to the temperatures at which measurements arc made-very difberent results are obtained. For cuample, in grosbeaks the slope of the acclimated metabolism-temperature curve extrapolates not to 38”C, but to about 50°C. Also, the :lcclimated metabolism varies according to whether the cooling Is cyclic or constant (25). Similarly, in cattle shifted from 63°F to 110°F over 6 hr the 0, consumption rose abruptly as heat regulation was established, whereas when similar cattle were subjected gradually over a 5-month period to a comparable elevation of environmental temperature (from 53°F to 95”F), their metabolism actually decreased ( 13). The metabolism-ambient temperature curve for white-throated sparrows estrapolatcd to body temperature at night when insulation was good, but e.\-trapolated to higher temperatures by day, when birds were active (7). In man, the metabolism-temperature curve varies greatly according to the conditions of measurement and time for equilibration. Acutelv mcasurcd curves may be curvilinear and mny extrapolate to about 25’C or slightly higher. This must be related to heat transfer between body core and periphery. Also, the curves in man are much steeper when evaporative stress is high than in still air, and the curves in csercise are diffcrcnt from those obtained at rest. Measurements made in men, naked but escrcising by bicycle to achieve comfort, extrapolate to 37°C (22). True acclimated curves have not been constructed at many temperatures for man. and present evidence fails to explain the marked difference between metabolism-ambient temperature curves for man and furred mammals.
I>espitc the similarities among animals mentioned above, man shows so many diffcrenccs from other animals that extrapolation is diffkuk. Some of the biologic characteristics which are prominent in man are the following: I. Man constitutes one biologic species. There is no reproductive isolation among populations or races. except that which may be socially imposed. It is most unlikely that modern man can ever evolve into subspecies, This means that genetically al1 men arc reproductively compatible. No other such cosmopolitan species exists. 2. Man shows remarkable phenotypic liability. Human populations are adapted
414
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to a wide range of climates-dry and moist air, cold and hot climates, reduced oxygen at high altitudes. This phenotypic lability permits many environmentally induced adaptations; the genetic limits for these arc extremely wide for man. As pointed out by Ernst Mayr (16), such phenotypic flexibility retards evolution and permits extension of range nongenetically. 3. Most of the adaptive characters of man are based on multiple alleles; these have been well analyzed for such proteins as hemoglobin (9). At the same time, pleiotropism is extreme; single cistrons lead to multiple effects. This is shown by correlated characters-for example, the relation between blood groups and certain types of carcinoma. 4. In human populations, balanced polymorphism is important. Individuals show great genetic diversity and in a population no two individuals (except for identical twins) are genetically identical. This means that certain recessive characters are bomld to be maintained at a fixed ratio under steady-stat<, conditions (as specified by the Hardy-V’einbcrg law), and the probability of eliminating such characters is virtually zero. Balanced polymorphism has been observed to impart certain advantages to populations, \vhcther in nature or in breeding cages (4). First, it means that for most characters there is a prcldominance of heteroxygotcs with the resulting biologic advantages of heterosis. At the same time, some characters are carried in cryptic form. Heterozygotcs tend to be more vigorous than homozygotes in general and to sho\v greatrr success in variable and stressful environments, whereas homozygotcs tend to he more influenced by the environment and heterozygotcs more resistant. Manced polymorphism can account for the maintained percentages of vnriolls characters in different populations. For csamplc, most individuals homozygous for sickle-cell anemia die before the age of 5 years, yet hetc~rozygotes are maintained at 40% in central Africa, 30% in India, and 17% in Greccc. The correlation of heterozygosity for sickle-cell anemia with resistance to malaria is well kno\vn. Similarly, blood types are maintained in balanced proportions in populations. 5. Man has evolved culturally very rapidly, biologically very slowly. Cnltural transmission provides for a wealth of adaptive traits. most of them bein housing and clothinghavioral. CulturalIy acquired traits-for example, permit survival in a midc range of climates. As a result, the microclimatc~ in which man lives is remarkably uniform; an Eskimo in his furs lives at a microclimatic tempcraturc similar to that of an Indian in the tropics. Cultural inhcritance and cultural evolution are much less important in the adaptation of animals to cnviromnents, although nongcnetically acquired behavior does kst. In conclusion. it must be emphasized that the patterns and molecular mcchanisms of both genetic and nongenetic adaptive variation in animals are worthy of study in their own right. This is part of our continuing effort to understand life processes, irrespective of direct application to man. The interactions between organisms and their environments are exceedingly compkx, and no single limiting mechanism exists for one c,nvironmentaI parameter in a given species. The time course of acclimation and the different effects of varied rates of change of an environmental parameter must be carefully examined for all adaptive responses. There is need for much research on the mechanism of
PRINCIPLES
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adaptive variation--studies at all levels of biologic organization. Extrapolation from animals to man must be viewed with extreme caution because of man’s biologic uniqueness. HEFEREXCES 1. :\DAMs, T., XXI) CO~INO, B. (:. ( 1948). Racial variations to a standardized cold strew J. Appt. Physiot. 12, 9-12. 2. DAS, A.. AND PROSSER, C. L. ( 1967). Biochemical changes in goldfish acclimated to II. Protein synthesis. Camp, Biochcm. Physiol. 21, 449367. high and low trmperatures. :3. &)HoLBI, 0. C., AND LEWIS, H. S. (19613). Terrestrial animals in cold: man in polar Sect. 4. Am. Physiol. Sot. Washington, D. C. pp. regions, III “Hantlhook of Physiology.” 4.35-436. “Genetic Polylllol-phism.” M.I.T. Press, Cambridge, Massachusetts. 4. FORD, E. B. ( 1965). Terrestrial animals in cold: recent stuclies of primitive man. 5. ~IAAlAiEL, I-1. T. (196.3). Sect, 4, pp. 113-43-f. Am. Physiol. Sot., Washington, D.C. Zn “Hantll~ook of Physiology,” 6. l~Oc:r~~c:~~a, P. W. ( 1966 ) Lactate dehydrogenases in poikilotherms: Definition of c~ complrs enzyme system. Corn)>. Biocl2. Ph!pio/. 18, 261-270. ;. fIUl,SON, J. \%'.. ASI) krlhlZEY, S. I,. ( 1966). Temprrictnre rcpulation and mrtaholic Pnsser dnn2mticlts. Camp. Binrhcm. rhythms in populations of the house sparrow, Plnysinl. 17, 203-217. N. IAMPIETRO, P. F., VAUGHAS, J, A., COLINAN, H. F., KREIDEH, 51. B., hlxx~cxr, I?., ANI) Bass, D. E. ( 1960). IIeat production from shivering. J. A~~JII. Physiol. 15, 632-634. 9, IXGRAHAAI, V. 1%. ( 1963). “The Hemoglobins in Cknetics and Evolution.” Colnmlk~ ITniv. Press, Sew York to. ]ASSKY, mechanisms in homeotherms. I,. ( 1965). Adaptability of heat production .4cto Unir. caroh2uc~ Biozo~:icu, I-9 1. course of oxygen consumption in rats during sllddcw II. JOIISSOS, II. ( 1967 ). Time e\powre to high mvironmental temperature. Li,k Sci. 6, 1221-1228. 12. ~osw., J., Ah'11 HA~wISGT~N, W. F. ( 1964 ). Role of pyrrolitline residnc~s in structure and stabilization of collagen. J. hfolec. Bid. 9, 269-287. 13. KIULEH, H. H. ( 1962). oxygen consumption in cattle in relation to rate of increaw in environmental temperatwe. Nntrrre 186, 972-973. 1.1. Eomt~n, H., I\IALLETT. (:. E., AND ADYE, J. ( 1957 ) Slolecular basis of l~iological stability to high trmperaturc. Proc. h’atl. Acud. Sci. 43, l64--177. 15. LADELL, W. S. S. (1963). Terrestrial animals in humid heat: man, pp. 62%660. In “Handlx~ok of Physiology,” Sect. 4, Am. Phy.riol. Sot., Washington, D. C. IG. ~IAY~, E. ( 196.3). “Animal Speciation and Evolution.” Harvard I!niv. Prrss, Cambridge, Massachasctts. 17. PRECHT, H. ( 195X). Concepts of temperature adaptation of unchanging reaction systems of coltl-l)looded animals. 111 “Physiological Adaptation.” ( C. L. Presser, etl. ) pp. 50-78. Am. Ph!~siol. Sot., Washington, D. C. 18. PROSSER, C. L. (1963). Perspectives of adaptation: theoretical aspects. In “Handbook of Physiology.” Sect. 4, pp. 11-25. Am. Physiol. Sot., Washington, D. C. 19. I’nosse~, C. L., AUU BRO\VV, F. A. ( 1961). “Comparativr Animal Physiology.” Sanndcrs, Philadelphia, Pennsylvania. 20. ~‘IKS~EH, C. L., .+.Ku FAHHI, E. ( 1965). Effects of temperature on conditioned reflexes and on nerve contlllction in fish. Z&w11. ocql. Phgsiol. 50, 91-101. 21. Ho0.1.s. B. J., AND PIVXSER. C. I,. ( 1962 ). Tcwlperatnre acclimation and the nervous s)~strm in fish. J. &q~f2. Viol. 39, 617-629. 22. S(:HOLANDER. P. I?.. AWERSOS, K. L., Kaoc. J., LOIIENTZE:N, F. V., ASL) STEEN, J. (1957). Critical temprratnre in I,apps. J. AJ,J,I. Ph!pio/. 10, 231-234. 2.3. SCHOLANIXR, I'. F., WALTERS, \'., Hots, R., AND IRVING, L. ( 1960). Body insnlation (If SI)IIW arctic d tropical nx~mnds ;und bir&s. Riol. Bull. 99, 225-236.
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