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Photooxidation and the evolution of circadian rhythmicity
J. theor. Biol. (1982) 97,77-82
Photooxidation and the Evolution Circadian Rhythmic@ J.
PAIETTA
Genetics Program ’ University of Illinois, Illinois 61801, U.S.A. (Received
of
Urbana,
10 November 1980, and in revised form 12 November 1981)
It is proposed that one of the original selective forces involved in the evolution of circadian rhythmicity was the joint effect of the light-dark cycle and the increasing level of free oxygen early in eukaryote evolution. Circadian rhythmicity would have provided a protective mechanism for minimizing the deleterious effects of the resulting diurnal photooxidative exposures. 1. Introduction The phenomenon of circadian rhythmicity, which is ubiquitous in eukaryotes (Biinning, 1973), allows the synchronization of biological processes to the daily cycle of light and dark. This type of temporal organization is thought to have a selective advantage in that organisms can perform particular activities (molecular to behavioral) at the “proper” time of day. Circadian rhythmicity is part of a continuum of biological oscillations of varying periodicity and was probably derived through the modification of existing cellular oscillations early in eukaryote evolution. An understanding of the selective forces involved in the evolution of circadian rhythmicity may lead to new approaches for an experimental analysis of its molecular basis. The starting assumptions made here are that circadian organization is present only in eukaryotes and that it developed concomitantly with the evolution of the eukaryotic state. In analyzing how circadian rhythmicity might have evolved one must then consider selective forces that were present in the early stages of eukaryote evolution and that continued onward in time. The more complex rhythmic phenomena and adaptations associated with multicellular organisms can be regarded as secondary developments and not basic to the evolutionary origin of circadian rhythmicity. Consideration needs to begin therefore with a fundamental case, that of an evolving unicellular organism. The selective advantage of circadian rhythmicity for 77 0022-5193/82/130077+06$03.00/0
@ 1982 Academic
Press Inc. (London)
Ltd.
78
J.
PAIETTA
unicellular organisms is poorly understood but is clearly the key to explaining how circadian rhythmicity evolved. What might have been the original selective force? Pittendrigh (1965, 1966) has suggested that the light-dark cycle was the “historical cause (selective agent) of circadian oscillations” and that these oscillations were an adaptation in dealing with the deleterious effects of light on cellular processes (for example, gene induction and replication). In this note, I examine from an evolutionary perspective the idea of a dual involvement of the light-dark cycle as the original selective agent leading to circadian organization and as a Zeitgeber (i.e. entraining or synchronizing agent). The hypothesis presented accounts simultaneously for a selective advantage of circadian rhythmicity and for major events occurring during eukaryote evolution. 2. Photooxidation
as a Selective Factor
The selective forces involved in the evolution of circadian rhythmicity are likely to be complex, but the emerging aerobic environment in the Precambrian (Cloud, 1968) may have been an important selective influence, The resulting selection pressure was the joint effect of the light-dark cycle and the increasing oxygen level early in the evolution of eukaryotes. The increasing level of free oxygen would have led to damaging photo-oxidative processes, depending on metastable oxygen species and varying in a daily cyclic manner. Under such conditions, the daily flux of visible and nearvisible light would be substantial enough to result in a wide range of photo-oxidative effects, An excited state oxygen species that is likely to be involved in the visible light effects is the singlet state, which has been implicated in a number of different photooxidation systems (Foote, 1976; Wilson & Hastings, 1970). Singlet oxygen, at least in the systems under consideration, would be ,an intermediary; it is formed by the quenching of the light-induced triplet state of an endogenous sensitizer and subsequently reacts with a substrate to yield an oxidized product. A number of other reactive oxygen species, such as the superoxide ion, which can be generated by electron transfer from a triplet sensitizer to oxygen could also result in damage to vital cellular constituents. Porphyrins and flavins are examples of endogenous photosensitizers. Oxygen-dependent near-visible (near-ultraviolet) light effects (Parrish ef al., 1978; Webb, 1977) also appear to be mediated by endogenous sensitizers and various radical intermediates. Oxygen has been a major factor in eukaryotic evolution because its occurrence in a free state resulted in a crisis, and a multiplicity of adaptations (Fridovich, 1977) were necessary for the transition from an anaerobic to
EVOLUTION
OF
CIRCADIAN
RHYTHMICITY
79
aerobic existance. The interactions of light and oxygen, present both during the early evolution of the eukaryotic state and thereafter, suggest that originally circadian rhythmicity was in part one of the many complex adaptations to the presence of free oxygen. Conceptually, one can delineate two protective mechanisms that would minimize the most damaging photo-oxidative effects on cellular systems: (1) prevention of photooxidative destruction of sensitive components through excited state quenching by pigments, and (2) rhythmic adjustment of light impaired cellular processes so that they minimized at the time of greatest photochemical hazard. An example of the first type of adaptation that acts to minimize photooxidative effects is provided by the protective pigments such as the carotenoids which, among other things, prevent photo-oxidative damage to cellular components (Krinsky, 1979). Carotenoids can function as quenchers of singlet oxygen and they are phylogenetically widespread. For the second type of adaptation, specific to eukaryotes, circadian rhythmicity is a protective response by providing a means of restricting (partially to totally) photosensitive processes to the dark. Thus besides the partial protection from the effects of light and oxygen by pigments and other means, further selective advantage can be obtained by regulating sensitive functions rhythmically. Additionally, the development of a cellular “resonant stability” brought about through the co-ordination of light inhibited/non-inhibited interacting systems relative to the light-dark cycle may have provided substantial selective advantage. This interpretation of circadian rhythmicity predicts that many cellular systems are set to different relative phase angles, not as the result of “frozen accidents” but because light sensitive processes are focal points for the co-ordination of cellular systems. The evolutionary view taken here suggests that the distribution of cellular functions is meaningful and that extensive data on cellular temporal organization would be a useful probe of the adaptive value and evolution of circadian rhythmicity. The circadian driving (or master) oscillation was probably not initially “forced” by the light-dark cycle, but instead coevolved with mechanisms to couple photosensitive and other systems to it. In this sense the evolution of circadian organization is to a large degree the evolution of the linkage between the driving oscillation and regulated functions. The linkage is likely to be complex, because most cellular systems depend on a number of factors that vary rhythmically (such as ion concentrations; energy charge; enzyme, substrate and product levels) and since there are probably severe evolutionary constraints on the degree of optimization through rhythmicity of numerous cellular functions.
80
J.
PAIETTA
Does the proposed selective advantage of circadian rhythmicity involving photo-oxidative protection still exist in extant lower eukaryotes? A number of cellular functions might provide systems to analyze for selective advantages. For example, the rhythmic regulation of mitochondrial function to minimize the effects of respiratory photo-inhibition is one possible selective advantage. The inhibition of mitochondrial function by oxygen dependent photo-inactivation of respiratory components (such as cytochrome oxidase) has been shown to have extensive effects on growth and cell division in a number of lower eukaryotes (Epel, 1973). In these lower eukaryotes, moderate levels of sunlight would have an inhibiting effect on respiration. As a specific case, some data for the fungus Neurospora are available on the light sensitivity of respiration and on circadian metabolic levels. Respiration in Neurospora is inhibited by visible light and the indentified photosensitive sites are two flavoproteins (NADH and succinate dehydrogenase), ubiquinone and mitochondrial thiol groups (Ramadan-Talib & Prebble, 1978). The circadian rhythm of carbon dioxide production measured in constant darkness shows peak levels during the subjective night (Woodward & Sargent, 1973). Thus respiration is phased so as to operate maximally in darkness. The data suggest that although respiration can continue in light with lowered efficiency (due to component inactivation or to other impairing effects) there is a selective advantage in maximizing metabolic levels when no impairment is present. Other possibilities, among many, of selective advantages include the following: (1) the rhythmic gating of cell division would allow this process to proceed efficiently by minimizing the inhibitory effects of light; and (2) the rhythmic regulation of photosensitive membrane components would minimize the loss of membrane function which can be caused by light (for examples of these visible and near-visible light effects, see Epel, 1973: Ulaszewski et al., 1979; Woodward, Cirillo & Edmunds, 1978). 3. Concluding
Remarks
Exposure of lower eukaryotes to photochemical processes on a daily basis that have deleterious effects on metabolic functions, membranes, nucleic acids and associated systems is clearly a selection pressure that would have been a contributing factor to the evolution of circadian temporal organization. Further, these cyclic photochemical processes may have generated certain selection pressures substantially unique to eukaryotes. Whether eukaryotes evolved by endosymbiosis or by other means, with the quantum jump in organizational level from the prokaryote to the eukaryote, new types of dynamic properties developed. Specifically, this is
EVOLUTION
OF
CIRCADIAN
RHYTHMICITY
81
the case in the complexity of eukaryotic cellular compartmentalization and associated interactions. In order to attain maximal efficiency for complex compartmentalized systems an intricate balance of cellular functions is required and such interactions would be prone to destabilization by photochemistry that is inhibitory only to certain subsystems. Therefore, if cellular functions were properly phased relative to the light-dark cycle then the light-dark cycle would not impose disruptive stress on cellular interactions. It follows, with reference to endosymbiotic theories of eukaryotic origins (Margulis, 1981), that circadian rhythmicity may have been genetically internalized as a part of the organelle integration process. As a starting hypothesis the photochemical effect associated with light and oxygen has been presented as an initiating selection pressure at the time eukaryotes were evolving. It should be noted that oxygen-independent photochemical effects which are caused primarily by ultraviolet light, while decreasing somewhat during the Precambrian due to the developing ozone layer (Cloud, 1968), could still have been a contributing factor. One approach towards an assessment of the relative importance of photooxidation as a selection pressure would be through the testing of lower eukaryotes for the presence and degree of circadian photosensitivities. In addition, this hypothesis provides a guideline for an analysis of the evolution and molecular basis of circadian rhythmicity. For example, since photosensitive and associated cellular functions were probably among the first to gain temporal regulation, the study of these functions may allow one to trace back to an early evolutionary stage of cellular temporal organization. I thank Drs D. L. Nanney and M. L. Sargent for helpful comments on the manuscript. REFERENCES B~~NNING, E. (1973). The Physiological Clock. Third revised edition, pp. 7-33. Berlin: Springer Verlag. CLOUD, P. E. (1968). Science 160,729. EPEL. B. L. (1973). In: Photophysiology (A. C. Giese, ed.), Vol. 8, pp. 209-225. New York: Plenum Press. FOOTE, C. S. (1976). In: Free Radicals in Biology (W. A. Pryor, ed.), Vol. 2, pp. 85-124. New York: Academic Press. FRIDOVICH, I. (1977). BioScience 27,462. KRINSKY. N. I. (1979). Pure Appl. Chem. 51,649. MARGULIS, L. (1981). Symbiosis in Ceil Euolurion. San Francisco: Freeman. PARRISH, J. A, ANDERSON, R. R., URBACH, F. & PINTS, D. (1978). UV-A. pp. 85-101. New York: Plenum Press. PITTENDRIGH, C. S. (1965). In: Science in the Sixties (D. L. Arm, ed.), pp. 96-111. Albuquerque: University of New Mexico. PITTENDRIGH. C. S. (1966). Z. Ppanzenphysiol. 54,275. RAMADAN-TABLIB, Z. & PREBBLE. J. (19781. Biochem. J. 176,767.
82
J.
PAIETTA
ULASZEWSKI, S., MAMOUNEAS, T., SHEN, W.-K., ROSENTHAL. P. J., WOODWARD, J. R.. CIRILLO, V. P. & EDMUNDS, L. N., JR. (1979). J. Bacfen’ol. 138, 523. WEBB, R. B. (1977). In: Photochemical and Photobiological Reviews (K. C. Smith, ed.), Vol. 2, pp. 169-262. New York: Plenum Press. WILSON, T. & HASTINGS, J. W. (1970). In: Photophysiology (A. C. Giese, ed.), Vol. 5, pp. 49-91. New York: Academic Press. WOODWARD. D. 0. & SARGENT, M. L. (1973). In: Behavior of Microorganisms (A. Perez-Miravete, ed.), p. 284. New York: Plenum Press. WOODWARD. J. R., CIRIL.LO, V. P. & EDMUNDS, L. N., JR. (1978). J. Bacterial. 133. 692.
Photooxidation and the Evolution Circadian Rhythmic@ J.
PAIETTA
Genetics Program ’ University of Illinois, Illinois 61801, U.S.A. (Received
of
Urbana,
10 November 1980, and in revised form 12 November 1981)
It is proposed that one of the original selective forces involved in the evolution of circadian rhythmicity was the joint effect of the light-dark cycle and the increasing level of free oxygen early in eukaryote evolution. Circadian rhythmicity would have provided a protective mechanism for minimizing the deleterious effects of the resulting diurnal photooxidative exposures. 1. Introduction The phenomenon of circadian rhythmicity, which is ubiquitous in eukaryotes (Biinning, 1973), allows the synchronization of biological processes to the daily cycle of light and dark. This type of temporal organization is thought to have a selective advantage in that organisms can perform particular activities (molecular to behavioral) at the “proper” time of day. Circadian rhythmicity is part of a continuum of biological oscillations of varying periodicity and was probably derived through the modification of existing cellular oscillations early in eukaryote evolution. An understanding of the selective forces involved in the evolution of circadian rhythmicity may lead to new approaches for an experimental analysis of its molecular basis. The starting assumptions made here are that circadian organization is present only in eukaryotes and that it developed concomitantly with the evolution of the eukaryotic state. In analyzing how circadian rhythmicity might have evolved one must then consider selective forces that were present in the early stages of eukaryote evolution and that continued onward in time. The more complex rhythmic phenomena and adaptations associated with multicellular organisms can be regarded as secondary developments and not basic to the evolutionary origin of circadian rhythmicity. Consideration needs to begin therefore with a fundamental case, that of an evolving unicellular organism. The selective advantage of circadian rhythmicity for 77 0022-5193/82/130077+06$03.00/0
@ 1982 Academic
Press Inc. (London)
Ltd.
78
J.
PAIETTA
unicellular organisms is poorly understood but is clearly the key to explaining how circadian rhythmicity evolved. What might have been the original selective force? Pittendrigh (1965, 1966) has suggested that the light-dark cycle was the “historical cause (selective agent) of circadian oscillations” and that these oscillations were an adaptation in dealing with the deleterious effects of light on cellular processes (for example, gene induction and replication). In this note, I examine from an evolutionary perspective the idea of a dual involvement of the light-dark cycle as the original selective agent leading to circadian organization and as a Zeitgeber (i.e. entraining or synchronizing agent). The hypothesis presented accounts simultaneously for a selective advantage of circadian rhythmicity and for major events occurring during eukaryote evolution. 2. Photooxidation
as a Selective Factor
The selective forces involved in the evolution of circadian rhythmicity are likely to be complex, but the emerging aerobic environment in the Precambrian (Cloud, 1968) may have been an important selective influence, The resulting selection pressure was the joint effect of the light-dark cycle and the increasing oxygen level early in the evolution of eukaryotes. The increasing level of free oxygen would have led to damaging photo-oxidative processes, depending on metastable oxygen species and varying in a daily cyclic manner. Under such conditions, the daily flux of visible and nearvisible light would be substantial enough to result in a wide range of photo-oxidative effects, An excited state oxygen species that is likely to be involved in the visible light effects is the singlet state, which has been implicated in a number of different photooxidation systems (Foote, 1976; Wilson & Hastings, 1970). Singlet oxygen, at least in the systems under consideration, would be ,an intermediary; it is formed by the quenching of the light-induced triplet state of an endogenous sensitizer and subsequently reacts with a substrate to yield an oxidized product. A number of other reactive oxygen species, such as the superoxide ion, which can be generated by electron transfer from a triplet sensitizer to oxygen could also result in damage to vital cellular constituents. Porphyrins and flavins are examples of endogenous photosensitizers. Oxygen-dependent near-visible (near-ultraviolet) light effects (Parrish ef al., 1978; Webb, 1977) also appear to be mediated by endogenous sensitizers and various radical intermediates. Oxygen has been a major factor in eukaryotic evolution because its occurrence in a free state resulted in a crisis, and a multiplicity of adaptations (Fridovich, 1977) were necessary for the transition from an anaerobic to
EVOLUTION
OF
CIRCADIAN
RHYTHMICITY
79
aerobic existance. The interactions of light and oxygen, present both during the early evolution of the eukaryotic state and thereafter, suggest that originally circadian rhythmicity was in part one of the many complex adaptations to the presence of free oxygen. Conceptually, one can delineate two protective mechanisms that would minimize the most damaging photo-oxidative effects on cellular systems: (1) prevention of photooxidative destruction of sensitive components through excited state quenching by pigments, and (2) rhythmic adjustment of light impaired cellular processes so that they minimized at the time of greatest photochemical hazard. An example of the first type of adaptation that acts to minimize photooxidative effects is provided by the protective pigments such as the carotenoids which, among other things, prevent photo-oxidative damage to cellular components (Krinsky, 1979). Carotenoids can function as quenchers of singlet oxygen and they are phylogenetically widespread. For the second type of adaptation, specific to eukaryotes, circadian rhythmicity is a protective response by providing a means of restricting (partially to totally) photosensitive processes to the dark. Thus besides the partial protection from the effects of light and oxygen by pigments and other means, further selective advantage can be obtained by regulating sensitive functions rhythmically. Additionally, the development of a cellular “resonant stability” brought about through the co-ordination of light inhibited/non-inhibited interacting systems relative to the light-dark cycle may have provided substantial selective advantage. This interpretation of circadian rhythmicity predicts that many cellular systems are set to different relative phase angles, not as the result of “frozen accidents” but because light sensitive processes are focal points for the co-ordination of cellular systems. The evolutionary view taken here suggests that the distribution of cellular functions is meaningful and that extensive data on cellular temporal organization would be a useful probe of the adaptive value and evolution of circadian rhythmicity. The circadian driving (or master) oscillation was probably not initially “forced” by the light-dark cycle, but instead coevolved with mechanisms to couple photosensitive and other systems to it. In this sense the evolution of circadian organization is to a large degree the evolution of the linkage between the driving oscillation and regulated functions. The linkage is likely to be complex, because most cellular systems depend on a number of factors that vary rhythmically (such as ion concentrations; energy charge; enzyme, substrate and product levels) and since there are probably severe evolutionary constraints on the degree of optimization through rhythmicity of numerous cellular functions.
80
J.
PAIETTA
Does the proposed selective advantage of circadian rhythmicity involving photo-oxidative protection still exist in extant lower eukaryotes? A number of cellular functions might provide systems to analyze for selective advantages. For example, the rhythmic regulation of mitochondrial function to minimize the effects of respiratory photo-inhibition is one possible selective advantage. The inhibition of mitochondrial function by oxygen dependent photo-inactivation of respiratory components (such as cytochrome oxidase) has been shown to have extensive effects on growth and cell division in a number of lower eukaryotes (Epel, 1973). In these lower eukaryotes, moderate levels of sunlight would have an inhibiting effect on respiration. As a specific case, some data for the fungus Neurospora are available on the light sensitivity of respiration and on circadian metabolic levels. Respiration in Neurospora is inhibited by visible light and the indentified photosensitive sites are two flavoproteins (NADH and succinate dehydrogenase), ubiquinone and mitochondrial thiol groups (Ramadan-Talib & Prebble, 1978). The circadian rhythm of carbon dioxide production measured in constant darkness shows peak levels during the subjective night (Woodward & Sargent, 1973). Thus respiration is phased so as to operate maximally in darkness. The data suggest that although respiration can continue in light with lowered efficiency (due to component inactivation or to other impairing effects) there is a selective advantage in maximizing metabolic levels when no impairment is present. Other possibilities, among many, of selective advantages include the following: (1) the rhythmic gating of cell division would allow this process to proceed efficiently by minimizing the inhibitory effects of light; and (2) the rhythmic regulation of photosensitive membrane components would minimize the loss of membrane function which can be caused by light (for examples of these visible and near-visible light effects, see Epel, 1973: Ulaszewski et al., 1979; Woodward, Cirillo & Edmunds, 1978). 3. Concluding
Remarks
Exposure of lower eukaryotes to photochemical processes on a daily basis that have deleterious effects on metabolic functions, membranes, nucleic acids and associated systems is clearly a selection pressure that would have been a contributing factor to the evolution of circadian temporal organization. Further, these cyclic photochemical processes may have generated certain selection pressures substantially unique to eukaryotes. Whether eukaryotes evolved by endosymbiosis or by other means, with the quantum jump in organizational level from the prokaryote to the eukaryote, new types of dynamic properties developed. Specifically, this is
EVOLUTION
OF
CIRCADIAN
RHYTHMICITY
81
the case in the complexity of eukaryotic cellular compartmentalization and associated interactions. In order to attain maximal efficiency for complex compartmentalized systems an intricate balance of cellular functions is required and such interactions would be prone to destabilization by photochemistry that is inhibitory only to certain subsystems. Therefore, if cellular functions were properly phased relative to the light-dark cycle then the light-dark cycle would not impose disruptive stress on cellular interactions. It follows, with reference to endosymbiotic theories of eukaryotic origins (Margulis, 1981), that circadian rhythmicity may have been genetically internalized as a part of the organelle integration process. As a starting hypothesis the photochemical effect associated with light and oxygen has been presented as an initiating selection pressure at the time eukaryotes were evolving. It should be noted that oxygen-independent photochemical effects which are caused primarily by ultraviolet light, while decreasing somewhat during the Precambrian due to the developing ozone layer (Cloud, 1968), could still have been a contributing factor. One approach towards an assessment of the relative importance of photooxidation as a selection pressure would be through the testing of lower eukaryotes for the presence and degree of circadian photosensitivities. In addition, this hypothesis provides a guideline for an analysis of the evolution and molecular basis of circadian rhythmicity. For example, since photosensitive and associated cellular functions were probably among the first to gain temporal regulation, the study of these functions may allow one to trace back to an early evolutionary stage of cellular temporal organization. I thank Drs D. L. Nanney and M. L. Sargent for helpful comments on the manuscript. REFERENCES B~~NNING, E. (1973). The Physiological Clock. Third revised edition, pp. 7-33. Berlin: Springer Verlag. CLOUD, P. E. (1968). Science 160,729. EPEL. B. L. (1973). In: Photophysiology (A. C. Giese, ed.), Vol. 8, pp. 209-225. New York: Plenum Press. FOOTE, C. S. (1976). In: Free Radicals in Biology (W. A. Pryor, ed.), Vol. 2, pp. 85-124. New York: Academic Press. FRIDOVICH, I. (1977). BioScience 27,462. KRINSKY. N. I. (1979). Pure Appl. Chem. 51,649. MARGULIS, L. (1981). Symbiosis in Ceil Euolurion. San Francisco: Freeman. PARRISH, J. A, ANDERSON, R. R., URBACH, F. & PINTS, D. (1978). UV-A. pp. 85-101. New York: Plenum Press. PITTENDRIGH, C. S. (1965). In: Science in the Sixties (D. L. Arm, ed.), pp. 96-111. Albuquerque: University of New Mexico. PITTENDRIGH. C. S. (1966). Z. Ppanzenphysiol. 54,275. RAMADAN-TABLIB, Z. & PREBBLE. J. (19781. Biochem. J. 176,767.
82
J.
PAIETTA
ULASZEWSKI, S., MAMOUNEAS, T., SHEN, W.-K., ROSENTHAL. P. J., WOODWARD, J. R.. CIRILLO, V. P. & EDMUNDS, L. N., JR. (1979). J. Bacfen’ol. 138, 523. WEBB, R. B. (1977). In: Photochemical and Photobiological Reviews (K. C. Smith, ed.), Vol. 2, pp. 169-262. New York: Plenum Press. WILSON, T. & HASTINGS, J. W. (1970). In: Photophysiology (A. C. Giese, ed.), Vol. 5, pp. 49-91. New York: Academic Press. WOODWARD. D. 0. & SARGENT, M. L. (1973). In: Behavior of Microorganisms (A. Perez-Miravete, ed.), p. 284. New York: Plenum Press. WOODWARD. J. R., CIRIL.LO, V. P. & EDMUNDS, L. N., JR. (1978). J. Bacterial. 133. 692.