Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

OPINION

Exploring phylogeny to find the function of sleep

Abstract

During sleep, animals do not eat, reproduce or forage. Sleeping animals are vulnerable to predation. Yet, the persistence of sleep despite evolutionary pressures, and the deleterious effects of sleep deprivation, indicate that sleep serves a function or functions that cannot easily be bypassed. Recent research demonstrates sleep to be phylogenetically far more pervasive than previously appreciated; it is possible that the very first animals slept. Here, we give an overview of sleep across various species, with the aim of determining its original purpose. Sleep exists in animals without cephalized nervous systems and can be influenced by non-neuronal signals, including those associated with metabolic rhythms. Together, these observations support the notion that sleep serves metabolic functions in neural and non-neural tissues.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Comparative approach for identifying the core function of sleep.

References

  1. 1.

    Zhdanova, I. V., Wang, S. Y., Leclair, O. U. & Danilova, N. P. Melatonin promotes sleep-like state in zebrafish. Brain Res. 903, 263–268 (2001).

    CAS  PubMed  Google Scholar 

  2. 2.

    Tobler, I. Effect of forced locomotion on the rest–activity cycle of the cockroach. Behav. Brain Res. 8, 351–360 (1983).

    CAS  PubMed  Google Scholar 

  3. 3.

    Raizen, D. M. et al. Lethargus is a Caenorhabditis elegans sleep-like state. Nature 451, 569–572 (2008).

    CAS  PubMed  Google Scholar 

  4. 4.

    Vorster, A. P., Krishnan, H. C., Cirelli, C. & Lyons, L. C. Characterization of sleep in Aplysia californica. Sleep 37, 1453–1463 (2014).

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Omond, S. et al. Inactivity is nycthemeral, endogenously generated, homeostatically regulated, and melatonin modulated in a free-living platyhelminth flatworm. Sleep 40, zsx124 (2017).

    Google Scholar 

  6. 6.

    Nath, R. D. et al. The jellyfish Cassiopea exhibits a sleep-like state. Curr. Biol. 27, 2984–2990 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Walker, J. M. & Berger, R. J. Sleep as an adaptation for energy conservation functionally related to hibernation and shallow torpor. Prog. Brain Res. 53, 255–278 (1980).

    CAS  PubMed  Google Scholar 

  8. 8.

    Tu, B. P. & McKnight, S. L. Metabolic cycles as an underlying basis of biological oscillations. Nat. Rev. Mol. Cell Biol. 7, 696–701 (2006).

    CAS  PubMed  Google Scholar 

  9. 9.

    Tu, B. P. & McKnight, S. L. The yeast metabolic cycle: insights into the life of a eukaryotic cell. Cold Spring Harb. Symp. Quant. Biol. 72, 339–343 (2007).

    CAS  PubMed  Google Scholar 

  10. 10.

    Schmidt, M. H. The energy allocation function of sleep: a unifying theory of sleep, torpor, and continuous wakefulness. Neurosci. Biobehav. Rev. 47, 122–153 (2014).

    PubMed  Google Scholar 

  11. 11.

    Buxton, O. M. et al. Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. Sci. Transl Med. 4, 129ra43 (2012).

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Van Cauter, E., Spiegel, K., Tasali, E. & Leproult, R. Metabolic consequences of sleep and sleep loss. Sleep Med. 9, S23–S28 (2008).

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Nedeltcheva, A. V. & Scheer, F. A. Metabolic effects of sleep disruption, links to obesity and diabetes. Curr. Opin. Endocrinol. Diabetes Obes. 21, 293–298 (2014).

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Campbell, S. S. & Tobler, I. Animal sleep: a review of sleep duration across phylogeny. Neurosci. Biobehav. Rev. 8, 269–300 (1984).

    CAS  PubMed  Google Scholar 

  15. 15.

    Franken, P., Chollet, D. & Tafti, M. The homeostatic regulation of sleep need is under genetic control. J. Neurosci. 21, 2610–2621 (2001).

    CAS  PubMed  Google Scholar 

  16. 16.

    Shaw, P. J., Cirelli, C., Greenspan, R. J. & Tononi, G. Correlates of sleep and waking in Drosophila melanogaster. Science 287, 1834–1837 (2000).

    CAS  PubMed  Google Scholar 

  17. 17.

    Hendricks, J. C. et al. Rest in Drosophila is a sleep-like state. Neuron 25, 129–138 (2000).

    CAS  PubMed  Google Scholar 

  18. 18.

    Tobler, I. I. & Neuner-Jehle, M. 24-h variation of vigilance in the cockroach Blaberus giganteus. J. Sleep Res. 1, 231–239 (1992).

    CAS  PubMed  Google Scholar 

  19. 19.

    Kaiser, W. & Steiner-Kaiser, J. Neuronal correlates of sleep, wakefulness and arousal in a diurnal insect. Nature 301, 707–709 (1983).

    CAS  PubMed  Google Scholar 

  20. 20.

    Singh, R. N. & Sulsston, J. E. Some observations on moulting in Caenorhabditis elegans. Nematologica 24, 63–71 (1978).

    Google Scholar 

  21. 21.

    Cassada, R. C. & Russell, R. L. The dauerlarva, a post-embryonic developmental variant of the nematode Caenorhabditis elegans. Dev. Biol. 46, 326–342 (1975).

    CAS  PubMed  Google Scholar 

  22. 22.

    Singh, K., Ju, J. Y., Walsh, M. B., DiIorio, M. A. & Hart, A. C. Deep conservation of genes required for both Drosphila melanogaster and Caenorhabditis elegans sleep includes a role for dopaminergic signaling. Sleep 37, 1439–1451 (2014).

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Schwarz, J., Lewandrowski, I. & Bringmann, H. Reduced activity of a sensory neuron during a sleep-like state in Caenorhabditis elegans. Curr. Biol. 21, R983–R984 (2011).

    CAS  PubMed  Google Scholar 

  24. 24.

    Nagy, S. et al. Homeostasis in C. elegans sleep is characterized by two behaviorally and genetically distinct mechanisms. eLife 3, e04380 (2014).

    PubMed  PubMed Central  Google Scholar 

  25. 25.

    Driver, R. J., Lamb, A. L., Wyner, A. J. & Raizen, D. M. DAF-16/FOXO regulates homeostasis of essential sleep-like behavior during larval transitions in C. elegans. Curr. Biol. 23, 501–506 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Kayser, M. S. & Biron, D. Sleep and development in genetically tractable model organisms. Genetics 203, 21–33 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Trojanowski, N. F. & Raizen, D. M. Call it worm sleep. Trends Neurosci. 39, 54–62 (2016).

    CAS  PubMed  Google Scholar 

  28. 28.

    Satterlie, R. A. Do jellyfish have central nervous systems? J. Exp. Biol. 214, 1215–1223 (2011).

    PubMed  Google Scholar 

  29. 29.

    Dzirasa, K. et al. Dopaminergic control of sleep-wake states. J. Neurosci. 26, 10577–10589 (2006).

    CAS  PubMed  Google Scholar 

  30. 30.

    Kume, K., Kume, S., Park, S. K., Hirsh, J. & Jackson, F. R. Dopamine is a regulator of arousal in the fruit fly. J. Neurosci. 25, 7377–7384 (2005).

    CAS  PubMed  Google Scholar 

  31. 31.

    Andretic, R., van Swinderen, B. & Greenspan, R. J. Dopaminergic modulation of arousal in Drosophila. Curr. Biol. 15, 1165–1175 (2005).

    CAS  PubMed  Google Scholar 

  32. 32.

    Turek, M., Besseling, J., Spies, J. P., Konig, S. & Bringmann, H. Sleep-active neuron specification and sleep induction require FLP-11 neuropeptides to systemically induce sleep. eLife 5, e12499 (2016).

    PubMed  PubMed Central  Google Scholar 

  33. 33.

    Nelson, M. D. et al. FMRFamide-like FLP-13 neuropeptides promote quiescence following heat stress in Caenorhabditis elegans. Curr. Biol. 24, 2406–2410 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Nath, R. D., Chow, E. S., Wang, H., Schwarz, E. M. & Sternberg, P. W. C. elegans stress-induced sleep emerges from the collective action of multiple neuropeptides. Curr. Biol. 26, 2446–2455 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Shang, Y. et al. Short neuropeptide F is a sleep-promoting inhibitory modulator. Neuron 80, 171–183 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Lenz, O., Xiong, J., Nelson, M. D., Raizen, D. M. & Williams, J. A. FMRFamide signaling promotes stress-induced sleep in Drosophila. Brain Behav. Immun. 47, 141–148 (2015).

    CAS  PubMed  Google Scholar 

  37. 37.

    Lee, D. A. et al. Genetic and neuronal regulation of sleep by neuropeptide VF. eLife 6, e25727 (2017).

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Deregnaucourt, S., Mitra, P. P., Feher, O., Pytte, C. & Tchernichovski, O. How sleep affects the developmental learning of bird song. Nature 433, 710–716 (2005).

    CAS  PubMed  Google Scholar 

  39. 39.

    Hendricks, J. C., Kirk, D., Panckeri, K., Miller, M. S. & Pack, A. I. Modafinil maintains waking in the fruit fly Drosophila melanogaster. Sleep 26, 139–146 (2003).

    PubMed  Google Scholar 

  40. 40.

    Panckeri, K. A., Schotland, H. M., Pack, A. I. & Hendricks, J. C. Modafinil decreases hypersomnolence in the English bulldog, a natural animal model of sleep-disordered breathing. Sleep 19, 626–631 (1996).

    CAS  PubMed  Google Scholar 

  41. 41.

    Rihel, J. et al. Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation. Science 327, 348–351 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Foltenyi, K., Greenspan, R. J. & Newport, J. W. Activation of EGFR and ERK by rhomboid signaling regulates the consolidation and maintenance of sleep in Drosophila. Nat. Neurosci. 10, 1160–1167 (2007).

    CAS  PubMed  Google Scholar 

  43. 43.

    Kushikata, T., Fang, J., Chen, Z., Wang, Y. & Krueger, J. M. Epidermal growth factor enhances spontaneous sleep in rabbits. Am. J. Physiol. 275, R509–R514 (1998).

    CAS  PubMed  Google Scholar 

  44. 44.

    Kramer, A. et al. Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signaling. Science 294, 2511–2515 (2001).

    CAS  PubMed  Google Scholar 

  45. 45.

    Van Buskirk, C. & Sternberg, P. W. Epidermal growth factor signaling induces behavioral quiescence in Caenorhabditis elegans. Nat. Neurosci. 10, 1300–1307 (2007).

    PubMed  Google Scholar 

  46. 46.

    Cirelli, C. & Tononi, G. Differences in brain gene expression between sleep and waking as revealed by mRNA differential display and cDNA microarray technology. J. Sleep Res. 8, S44–S52 (1999).

    Google Scholar 

  47. 47.

    Naidoo, N., Giang, W., Galante, R. J. & Pack, A. I. Sleep deprivation induces the unfolded protein response in mouse cerebral cortex. J. Neurochem. 92, 1150–1157 (2005).

    CAS  PubMed  Google Scholar 

  48. 48.

    Jones, S., Pfister-Genskow, M., Benca, R. M. & Cirelli, C. Molecular correlates of sleep and wakefulness in the brain of the white-crowned sparrow. J. Neurochem. 105, 46–62 (2008).

    CAS  PubMed  Google Scholar 

  49. 49.

    Sanders, J., Scholz, M., Merutka, I. & Biron, D. Distinct unfolded protein responses mitigate or mediate effects of nonlethal deprivation of C. elegans sleep in different tissues. BMC Biol. 15, 67 (2017).

    PubMed  PubMed Central  Google Scholar 

  50. 50.

    Yurgel, M. E., Masek, P., DiAngelo, J. & Keene, A. C. Genetic dissection of sleep–metabolism interactions in the fruit fly. J. Comp. Physiol. A 201, 869–877 (2015).

    CAS  Google Scholar 

  51. 51.

    Seugnet, L., Galvin, J. E., Suzuki, Y., Gottschalk, L. & Shaw, P. J. Persistent short-term memory defects following sleep deprivation in a Drosophila model of Parkinson disease. Sleep 32, 984–992 (2009).

    PubMed  PubMed Central  Google Scholar 

  52. 52.

    Siegel, J. M. Clues to the functions of mammalian sleep. Nature 437, 1264–1271 (2005).

    CAS  PubMed  Google Scholar 

  53. 53.

    Lyamin, O., Pryaslova, J., Lance, V. & Siegel, J. Animal behaviour: continuous activity in cetaceans after birth. Nature 435, 1177 (2005).

    CAS  PubMed  Google Scholar 

  54. 54.

    Lesku, J. A. et al. Adaptive sleep loss in polygynous pectoral sandpipers. Science 337, 1654–1658 (2012).

    CAS  PubMed  Google Scholar 

  55. 55.

    Rattenborg, N. C. et al. Migratory sleeplessness in the white-crowned sparrow (Zonotrichia leucophrys gambelii). PLOS Biol. 2, E212 (2004).

    PubMed  PubMed Central  Google Scholar 

  56. 56.

    Rattenborg, N. C. et al. Evidence that birds sleep in mid-flight. Nat. Commun. 7, 12468 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Mukhametov, L. M. Unihemispheric slow-wave sleep in the Amazonian dolphin Inia geoffrensis. Neurosci. Lett. 79, 128–132 (1987).

    CAS  PubMed  Google Scholar 

  58. 58.

    Siegel, J. M. Do all animals sleep? Trends Neurosci. 31, 208–213 (2008).

    CAS  PubMed  Google Scholar 

  59. 59.

    Fontvieille, A. M., Rising, R., Spraul, M., Larson, D. E. & Ravussin, E. Relationship between sleep stages and metabolic rate in humans. Am. J. Physiol. 267, E732–E737 (1994).

    CAS  PubMed  Google Scholar 

  60. 60.

    Brebbia, D. R. & Altshuler, K. Z. Oxygen consumption rate and electroencephalographic stage of sleep. Science 150, 1621–1623 (1965).

    CAS  PubMed  Google Scholar 

  61. 61.

    Dement, W. & Kleitman, N. Cyclic variations in EEG during sleep and their relation to eye movements, body motility, and dreaming. Electroencephalogr. Clin. Neurophysiol. 9, 673–690 (1957).

    CAS  PubMed  Google Scholar 

  62. 62.

    Rechtschaffen, A. & Kales, A. (eds) A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects (US National Institute of Neurological Diseases and Blindness, 1968).

  63. 63.

    Jouvet, M. & Michel, F. Electromyographic correlations of sleep in the chronic decorticate & mesencephalic cat [French]. C. R. Seances Soc. Biol. Fil. 153, 422–425 (1959).

    CAS  PubMed  Google Scholar 

  64. 64.

    Shein-Idelson, M., Ondracek, J. M., Liaw, H. P., Reiter, S. & Laurent, G. Slow waves, sharp waves, ripples, and REM in sleeping dragons. Science 352, 590–595 (2016).

    CAS  PubMed  Google Scholar 

  65. 65.

    Nichols, A. L. A., Eichler, T., Latham, R. & Zimmer, M. A global brain state underlies C. elegans sleep behavior. Science 356, eaam6851 (2017).

    PubMed  Google Scholar 

  66. 66.

    Yap, M. H. W. et al. Oscillatory brain activity in spontaneous and induced sleep stages in flies. Nat. Commun. 8, 1815 (2017).

    PubMed  PubMed Central  Google Scholar 

  67. 67.

    Nitz, D. A., van Swinderen, B., Tononi, G. & Greenspan, R. J. Electrophysiological correlates of rest and activity in Drosophila melanogaster. Curr. Biol. 12, 1934–1940 (2002).

    CAS  PubMed  Google Scholar 

  68. 68.

    Ramon, F., Hernandez-Falcon, J., Nguyen, B. & Bullock, T. H. Slow wave sleep in crayfish. Proc. Natl Acad. Sci. USA 101, 11857–11861 (2004).

    CAS  PubMed  Google Scholar 

  69. 69.

    Trojanowski, N. F., Nelson, M. D., Flavell, S. W., Fang-Yen, C. & Raizen, D. M. Distinct mechanisms underlie quiescence during two Caenorhabditis elegans sleep-like states. J. Neurosci. 35, 14571–14584 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. 70.

    van Alphen, B., Yap, M. H., Kirszenblat, L., Kottler, B. & van Swinderen, B. A dynamic deep sleep stage in Drosophila. J. Neurosci. 33, 6917–6927 (2013).

    PubMed  Google Scholar 

  71. 71.

    Blumberg, M. S., Coleman, C. M., Gerth, A. I. & McMurray, B. Spatiotemporal structure of REM sleep twitching reveals developmental origins of motor synergies. Curr. Biol. 23, 2100–2109 (2013).

    CAS  PubMed  Google Scholar 

  72. 72.

    Dilley, L. C., Vigderman, A., Williams, C. E. & Kayser, M. S. Behavioral and genetic features of sleep ontogeny in Drosophila. Sleep 41, zsy086 (2018).

    Google Scholar 

  73. 73.

    Hobson, J. A. Sleep is of the brain, by the brain and for the brain. Nature 437, 1254–1256 (2005).

    CAS  PubMed  Google Scholar 

  74. 74.

    Saper, C. B., Scammell, T. E. & Lu, J. Hypothalamic regulation of sleep and circadian rhythms. Nature 437, 1257–1263 (2005).

    CAS  PubMed  Google Scholar 

  75. 75.

    Joiner, W. J., Crocker, A., White, B. H. & Sehgal, A. Sleep in Drosophila is regulated by adult mushroom bodies. Nature 441, 757–760 (2006).

    CAS  PubMed  Google Scholar 

  76. 76.

    Bringmann, H. Sleep-active neurons: conserved motors of sleep. Genetics 208, 1279–1289 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. 77.

    Lim, J. & Dinges, D. F. Sleep deprivation and vigilant attention. Ann. NY Acad. Sci. 1129, 305–322 (2008).

    PubMed  Google Scholar 

  78. 78.

    Kirszenblat, L. & van Swinderen, B. The yin and yang of sleep and attention. Trends Neurosci. 38, 776–786 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Cirelli, C. & Tononi, G. Sleep and synaptic homeostasis. Sleep 38, 161–162 (2015).

    PubMed  PubMed Central  Google Scholar 

  80. 80.

    Krueger, J. M. & Tononi, G. Local use-dependent sleep; synthesis of the new paradigm. Curr. Top. Med. Chem. 11, 2490–2492 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. 81.

    Vyazovskiy, V. V. & Harris, K. D. Sleep and the single neuron: the role of global slow oscillations in individual cell rest. Nat. Rev. Neurosci. 14, 443–451 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Krueger, J. M., Huang, Y. H., Rector, D. M. & Buysse, D. J. Sleep: a synchrony of cell activity-driven small network states. Eur. J. Neurosci. 38, 2199–2209 (2013).

    PubMed  PubMed Central  Google Scholar 

  83. 83.

    Saper, C. B., Fuller, P. M., Pedersen, N. P., Lu, J. & Scammell, T. E. Sleep state switching. Neuron 68, 1023–1042 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84.

    Hinard, V. et al. Key electrophysiological, molecular, and metabolic signatures of sleep and wakefulness revealed in primary cortical cultures. J. Neurosci. 32, 12506–12517 (2012).

    CAS  PubMed  Google Scholar 

  85. 85.

    Jewett, K. A. et al. Tumor necrosis factor enhances the sleep-like state and electrical stimulation induces a wake-like state in co-cultures of neurons and glia. Eur. J. Neurosci. 42, 2078–2090 (2015).

    PubMed  PubMed Central  Google Scholar 

  86. 86.

    Laposky, A. et al. Deletion of the mammalian circadian clock gene BMAL1/Mop3 alters baseline sleep architecture and the response to sleep deprivation. Sleep 28, 395–409 (2005).

    PubMed  Google Scholar 

  87. 87.

    Ehlen, J. C. et al. Bmal1 function in skeletal muscle regulates sleep. eLife 6, e26557 (2017).

    PubMed  PubMed Central  Google Scholar 

  88. 88.

    Williams, J. A., Sathyanarayanan, S., Hendricks, J. C. & Sehgal, A. Interaction between sleep and the immune response in Drosophila: a role for the NFκB Relish. Sleep 30, 389–400 (2007).

    PubMed  PubMed Central  Google Scholar 

  89. 89.

    Bennett, H. L. et al. Normal sleep bouts are not essential for C. elegans survival and FoxO is important for compensatory changes in sleep. BMC Neurosci. 19, 10 (2018).

    PubMed  PubMed Central  Google Scholar 

  90. 90.

    Iannacone, M. J. et al. The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans. eLife 6, e19837 (2017).

    PubMed  PubMed Central  Google Scholar 

  91. 91.

    Smith, C. L. et al. Novel cell types, neurosecretory cells, and body plan of the early-diverging metazoan Trichoplax adhaerens. Curr. Biol. 24, 1565–1572 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Senatore, A., Reese, T. S. & Smith, C. L. Neuropeptidergic integration of behavior in Trichoplax adhaerens, an animal without synapses. J. Exp. Biol. 220, 3381–3390 (2017).

    PubMed  PubMed Central  Google Scholar 

  93. 93.

    Smith, C. L., Pivovarova, N. & Reese, T. S. Coordinated feeding behavior in Trichoplax, an animal without synapses. PLOS ONE 10, e0136098 (2015).

    PubMed  PubMed Central  Google Scholar 

  94. 94.

    Varoqueaux, F. et al. High cell diversity and complex peptidergic signaling underlie placozoan behavior. Curr. Biol. 28, 3495–3501 (2018).

    CAS  PubMed  Google Scholar 

  95. 95.

    Sakarya, O. et al. A post-synaptic scaffold at the origin of the animal kingdom. PLOS ONE 2, e506 (2007).

    PubMed  PubMed Central  Google Scholar 

  96. 96.

    Nickel, M. Kinetics and rhythm of body contractions in the sponge Tethya wilhelma (Porifera: Demospongiae). J. Exp. Biol. 207, 4515–4524 (2004).

    PubMed  Google Scholar 

  97. 97.

    Ludeman, D. A., Farrar, N., Riesgo, A., Paps, J. & Leys, S. P. Evolutionary origins of sensation in metazoans: functional evidence for a new sensory organ in sponges. BMC Evol. Biol. 14, 3 (2014).

    PubMed  PubMed Central  Google Scholar 

  98. 98.

    de Mairan, J. J. D. Histoire de l’Académie Royale des Sciences (Année 1729) 35–36 (Imprimerie Royale, 1731).

  99. 99.

    Hattori, A. et al. Identification of melatonin in plants and its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates. Biochem. Mol. Biol. Int. 35, 627–634 (1995).

    CAS  PubMed  Google Scholar 

  100. 100.

    Arnao, M. B. & Hernandez-Ruiz, J. Functions of melatonin in plants: a review. J. Pineal Res. 59, 133–150 (2015).

    CAS  PubMed  Google Scholar 

  101. 101.

    Poroyko, V. A. et al. Chronic sleep disruption alters gut microbiota, induces systemic and adipose tissue inflammation and insulin resistance in mice. Sci. Rep. 6, 35405 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. 102.

    Szuperak, M. et al. A sleep state in Drosophila larvae required for neural stem cell proliferation. eLife 7, e33220 (2018).

    PubMed  PubMed Central  Google Scholar 

  103. 103.

    Kayser, M. S., Yue, Z. & Sehgal, A. A critical period of sleep for development of courtship circuitry and behavior in Drosophila. Science 344, 269–274 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. 104.

    Roffwarg, H. P., Muzio, J. N. & Dement, W. C. Ontogenetic development of the human sleep–dream cycle. Science 152, 604–619 (1966).

    CAS  PubMed  Google Scholar 

  105. 105.

    Davis, K. C. & Raizen, D. M. A mechanism for sickness sleep: lessons from invertebrates. J. Physiol. 595, 5415–5424 (2016).

    Google Scholar 

  106. 106.

    Prather, A. A., Janicki-Deverts, D., Hall, M. H. & Cohen, S. Behaviorally assessed sleep and susceptibility to the common cold. Sleep 38, 1353–1359 (2015).

    PubMed  PubMed Central  Google Scholar 

  107. 107.

    Kuo, T. H. & Williams, J. A. Increased sleep promotes survival during a bacterial infection in Drosophila. Sleep 37, 1077–1086 (2014).

    PubMed  PubMed Central  Google Scholar 

  108. 108.

    Hill, A. J., Mansfield, R., Lopez, J. M., Raizen, D. M. & Van Buskirk, C. Cellular stress induces a protective sleep-like state in C. elegans. Curr. Biol. 24, 2399–2405 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. 109.

    Huang, T. C., Tu, J., Chow, T. J. & Chen, T. H. Circadian rhythm of the prokaryote Synechococcus sp. RF-1. Plant Physiol. 92, 531–533 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. 110.

    Postgate, J. Nitrogen Fixation 3rd edn (Cambridge Univ. Press, 1998).

  111. 111.

    Liu, Y. et al. Circadian orchestration of gene expression in cyanobacteria. Genes Dev. 9, 1469–1478 (1995).

    CAS  PubMed  Google Scholar 

  112. 112.

    Tu, B. P., Kudlicki, A., Rowicka, M. & McKnight, S. L. Logic of the yeast metabolic cycle: temporal compartmentalization of cellular processes. Science 310, 1152–1158 (2005).

    CAS  PubMed  Google Scholar 

  113. 113.

    Chen, Z., Odstrcil, E. A., Tu, B. P. & McKnight, S. L. Restriction of DNA replication to the reductive phase of the metabolic cycle protects genome integrity. Science 316, 1916–1919 (2007).

    CAS  PubMed  Google Scholar 

  114. 114.

    Xie, L. et al. Sleep drives metabolite clearance from the adult brain. Science 342, 373–377 (2013).

    CAS  Google Scholar 

  115. 115.

    Maret, S. et al. Homer1a is a core brain molecular correlate of sleep loss. Proc. Natl Acad. Sci. USA 104, 20090–20095 (2007).

    CAS  PubMed  Google Scholar 

  116. 116.

    Cirelli, C., Gutierrez, C. M. & Tononi, G. Extensive and divergent effects of sleep and wakefulness on brain gene expression. Neuron 41, 35–43 (2004).

    CAS  Google Scholar 

  117. 117.

    Anafi, R. C. et al. Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues. BMG Genomics 14, 362 (2013).

    CAS  Google Scholar 

  118. 118.

    Mackiewicz, M. et al. Macromolecule biosynthesis: a key function of sleep. Physiol. Genom. 31, 441–457 (2007).

    CAS  Google Scholar 

  119. 119.

    Thompson, C. L. et al. Molecular and anatomical signatures of sleep deprivation in the mouse brain. Front. Neurosci. 4, 165 (2010).

    PubMed  PubMed Central  Google Scholar 

  120. 120.

    Archer, S. N. et al. Mistimed sleep disrupts circadian regulation of the human transcriptome. Proc. Natl Acad. Sci. USA 111, E682–E691 (2014).

    CAS  PubMed  Google Scholar 

  121. 121.

    Balsalobre, A. et al. Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science 289, 2344–2347 (2000).

    CAS  PubMed  Google Scholar 

  122. 122.

    Kajimoto, J., Matsumura, R., Node, K. & Akashi, M. Potential role of the pancreatic hormone insulin in resetting human peripheral clocks. Genes Cells 23, 393–399 (2018).

    CAS  PubMed  Google Scholar 

  123. 123.

    Hardman, J. A., Haslam, I. S., Farjo, N., Farjo, B. & Paus, R. Thyroxine differentially modulates the peripheral clock: lessons from the human hair follicle. PLOS ONE 10, e0121878 (2015).

    PubMed  PubMed Central  Google Scholar 

  124. 124.

    Brown, S. A., Zumbrunn, G., Fleury-Olela, F., Preitner, N. & Schibler, U. Rhythms of mammalian body temperature can sustain peripheral circadian clocks. Curr. Biol. 12, 1574–1583 (2002).

    CAS  PubMed  Google Scholar 

  125. 125.

    Franken, P. & Dijk, D. J. Circadian clock genes and sleep homeostasis. Eur. J. Neurosci. 29, 1820–1829 (2009).

    CAS  PubMed  Google Scholar 

  126. 126.

    Durkin, J. & Aton, S. J. Sleep-dependent potentiation in the visual system is at odds with the synaptic homeostasis hypothesis. Sleep 39, 155–159 (2016).

    PubMed  PubMed Central  Google Scholar 

  127. 127.

    Liu, Z. W., Faraguna, U., Cirelli, C., Tononi, G. & Gao, X. B. Direct evidence for wake-related increases and sleep-related decreases in synaptic strength in rodent cortex. J. Neurosci. 30, 8671–8675 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. 128.

    Hengen, K. B., Torrado Pacheco, A., McGregor, J. N., Van Hooser, S. D. & Turrigiano, G. G. Neuronal firing rate homeostasis is inhibited by sleep and promoted by wake. Cell 165, 180–191 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. 129.

    Tononi, G. & Cirelli, C. Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration. Neuron 81, 12–34 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. 130.

    Raichle, M. E. & Mintun, M. A. Brain work and brain imaging. Annu. Rev. Neurosci. 29, 449–476 (2006).

    CAS  PubMed  Google Scholar 

  131. 131.

    Lesku, J. A. & Ly, L. M. T. Sleep origins: restful jellyfish are sleeping jellyfish. Curr. Biol. 27, R1060–R1062 (2017).

    CAS  PubMed  Google Scholar 

  132. 132.

    Weljie, A. M. et al. Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt. Proc. Natl Acad. Sci. USA 112, 2569–2574 (2015).

    CAS  PubMed  Google Scholar 

  133. 133.

    Davies, S. K. et al. Effect of sleep deprivation on the human metabolome. Proc. Natl Acad. Sci. USA 111, 10761–10766 (2014).

    CAS  PubMed  Google Scholar 

  134. 134.

    Tu, B. P. et al. Cyclic changes in metabolic state during the life of a yeast cell. Proc. Natl Acad. Sci. USA 104, 16886–16891 (2007).

    CAS  PubMed  Google Scholar 

  135. 135.

    Yurgel, M. E. et al. Ade2 functions in the Drosophila fat body to promote sleep. G3 8, 3385–3395 (2018).

    PubMed  Google Scholar 

  136. 136.

    Thimgan, M. S., Suzuki, Y., Seugnet, L., Gottschalk, L. & Shaw, P. J. The perilipin homologue, lipid storage droplet 2, regulates sleep homeostasis and prevents learning impairments following sleep loss. PLOS Biol. 8, e1000466 (2010).

    PubMed  PubMed Central  Google Scholar 

  137. 137.

    Skora, S., Mende, F. & Zimmer, M. Energy scarcity promotes a brain-wide sleep state modulated by insulin signaling in C. elegans. Cell Rep. 22, 953–966 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. 138.

    Rechtschaffen, A., Bergmann, B. M., Everson, C. A., Kushida, C. A. & Gilliland, M. A. Sleep deprivation in the rat: X. Integration and discussion of the findings. Sleep 12, 68–87 (1989).

    CAS  PubMed  Google Scholar 

  139. 139.

    Shaw, P. J., Tononi, G., Greenspan, R. J. & Robinson, D. F. Stress response genes protect against lethal effects of sleep deprivation in Drosophila. Nature 417, 287–291 (2002).

    CAS  PubMed  Google Scholar 

  140. 140.

    Rechtschaffen, A. Current perspectives on the function of sleep. Perspect. Biol. Med. 41, 359–390 (1998).

    CAS  PubMed  Google Scholar 

  141. 141.

    Everson, C. A. Clinical assessment of blood leukocytes, serum cytokines, and serum immunoglobulins as responses to sleep deprivation in laboratory rats. Am. J. Physiol. Regul. Integr.Comp. Physiol. 289, R1054–R1063 (2005).

    CAS  PubMed  Google Scholar 

  142. 142.

    McHill, A. W. & Wright, K. P. Jr. Role of sleep and circadian disruption on energy expenditure and in metabolic predisposition to human obesity and metabolic disease. Obes. Rev. 18, S15–S24 (2017).

    Google Scholar 

  143. 143.

    Naidoo, N. et al. Aging and sleep deprivation induce the unfolded protein response in the pancreas: implications for metabolism. Aging Cell 13, 131–141 (2014).

    CAS  PubMed  Google Scholar 

  144. 144.

    Rechtschaffen, A., Gilliland, M. A., Bergmann, B. M. & Winter, J. B. Physiological correlates of prolonged sleep deprivation in rats. Science 221, 182–184 (1983).

    CAS  PubMed  Google Scholar 

  145. 145.

    Walker, M. P. & Stickgold, R. Sleep, memory, and plasticity. Annu. Rev. Psychol. 57, 139–166 (2006).

    PubMed  Google Scholar 

  146. 146.

    Benington, J. H. & Frank, M. G. Cellular and molecular connections between sleep and synaptic plasticity. Prog. Neurobiol. 69, 71–101 (2003).

    CAS  PubMed  Google Scholar 

  147. 147.

    Zhang, J. et al. Extended wakefulness: compromised metabolics in and degeneration of locus ceruleus neurons. J. Neurosci. 34, 4418–4431 (2014).

    PubMed  PubMed Central  Google Scholar 

  148. 148.

    Spiegel, K., Leproult, R. & Van Cauter, E. Impact of sleep debt on metabolic and endocrine function. Lancet 354, 1435–1439 (1999).

    CAS  PubMed  Google Scholar 

  149. 149.

    Imeri, L. & Opp, M. R. How (and why) the immune system makes us sleep. Nat. Rev. Neurosci. 10, 199–210 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. 150.

    Dubowy, C. et al. Genetic dissociation of daily sleep and sleep following thermogenetic sleep deprivation in Drosophila. Sleep 39, 1083–1095 (2016).

    PubMed  PubMed Central  Google Scholar 

  151. 151.

    Seidner, G. et al. Identification of neurons with a privileged role in sleep homeostasis in Drosophila melanogaster. Curr. Biol. 25, 2928–2938 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. 152.

    Alvarenga, T. A., Andersen, M. L., Papale, L. A., Antunes, I. B. & Tufik, S. Influence of long-term food restriction on sleep pattern in male rats. Brain Res. 1057, 49–56 (2005).

    CAS  PubMed  Google Scholar 

  153. 153.

    Slocumb, M. E. et al. Enhanced sleep is an evolutionarily adaptive response to starvation stress in Drosophila. PLOS ONE 10, e0131275 (2015).

    PubMed  PubMed Central  Google Scholar 

  154. 154.

    Duboue, E. R., Keene, A. C. & Borowsky, R. L. Evolutionary convergence on sleep loss in cavefish populations. Curr. Biol. 21, 671–676 (2011).

    CAS  PubMed  Google Scholar 

  155. 155.

    Keene, A. C. et al. Clock and cycle limit starvation-induced sleep loss in Drosophila. Curr. Biol. 20, 1209–1215 (2010).

    CAS  PubMed  Google Scholar 

  156. 156.

    Goetting, D. L., Soto, R. & Van Buskirk, C. Food-dependent plasticity in Caenorhabditis elegans stress-induced sleep is mediated by TOR-FOXA and TGF-β signaling. Genetics 209, 1183–1195 (2018).

    PubMed  Google Scholar 

  157. 157.

    Ramm, P. & Smith, C. T. Rates of cerebral protein synthesis are linked to slow wave sleep in the rat. Physiol. Behav. 48, 749–753 (1990).

    CAS  PubMed  Google Scholar 

  158. 158.

    Simor, A. et al. The short- and long-term proteomic effects of sleep deprivation on the cortical and thalamic synapses. Mol. Cell. Neurosci. 79, 64–80 (2017).

    CAS  PubMed  Google Scholar 

  159. 159.

    Siegel, J. M. Sleep viewed as a state of adaptive inactivity. Nat. Rev. Neurosci. 10, 747–753 (2009).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank A. Rohacek and S. Belfer for comments. R.C.A. is supported by US Defense Advanced Research Projects Agency grant D17AP00003; M.S.K. is supported by K08NS090461 (US National Institutes of Health), a Burroughs Wellcome Career Award for Medical Scientists, a March of Dimes Basil O’Connor Scholar Award and a Sloan Research Fellowship; and D.M.R. is supported by R01NS088432 (US National Institutes of Health).

Reviewer information

Nature Reviews Neuroscience thanks D. Prober, M. Zimmer and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Author information

Affiliations

Authors

Contributions

All authors wrote the manuscript.

Corresponding author

Correspondence to David M. Raizen.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Anafi, R.C., Kayser, M.S. & Raizen, D.M. Exploring phylogeny to find the function of sleep. Nat Rev Neurosci 20, 109–116 (2019). https://doi.org/10.1038/s41583-018-0098-9

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing