Did a small thermosensitive intron contribute to the temperate adaptation of Drosophila melanogaster?

Main Article Content

Isaac Edery

Abstract

Drosophila melanogaster was first used for research in the early 1900’s by scientists located in the northeastern corridor of the United States, gaining prominence with the establishment of the famous “fly room” by Thomas Hunt Morgan at Columbia University circa1908. Several reasons for using D. melanogaster in research are well known; easy and inexpensive to breed, short lifespan, amongst others. But why was this insect species flourishing in a temperate northeast region of the New World during the late 1800’s when they originated in the tropical forests of sub-Saharan Africa millions of years ago? The purpose of this review is to provide an overview of the experimental underpinnings for a temperature sensitive mechanism that likely contributed to the rather unique ability of Drosophila melanogaster to successfully colonize temperate regions on a global scale. It also furnishes an interesting historical insight into how ancestral genetics serendipitously held the keys to the journey of D. melanogaster becoming such a popular research organism. While numerous papers have been published detailing different aspects of the work, this is the first comprehensive review. Herein, I discuss the discovery of a small thermosensitive intron in D. melanogaster (termed dmpi8) that controls midday siesta levels. Like many day-active animals, Drosophila exhibits a robust genetically based midday siesta that is protective in warm climates. Yet long bouts of daytime inactivity might be counterproductive in temperate climates, especially since daylength in these regions is shorter during the cooler months. Evidence discussed in this review strongly indicates that targeting of dmpi8 splicing efficiency by natural selection enhanced the ability of D. melanogaster to scale daytime sleep levels commensurate with a wide range of local climates. Surprisingly, dmpi8 splicing regulates midday siesta levels in trans by controlling the expression of a nearby anti-siesta gene called daywake. The “fortuitous” genetic arrangement of a thermosensitive intron in proximity to an anti-siesta gene might have contributed to the cosmopolitan nature of D. melanogaster and its historical journey in becoming a popular research organism.

Article Details

How to Cite
EDERY, Isaac. Did a small thermosensitive intron contribute to the temperate adaptation of Drosophila melanogaster?. Medical Research Archives, [S.l.], v. 11, n. 11, nov. 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4624>. Date accessed: 03 dec. 2024. doi: https://doi.org/10.18103/mra.v11i11.4624.
Section
Research Articles

References

1. O'Grady, P.M. & DeSalle, R. Phylogeny of the Genus Drosophila. Genetics 209, 1-25 (2018).10.1534/genetics.117.300583

2. Bellen, H.J., Tong, C. & Tsuda, H. 100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future. Nat Rev Neurosci 11, 514-22 (2010).10.1038/nrn2839

3. Letsou, A. & Bohmann, D. Small flies--big discoveries: nearly a century of Drosophila genetics and development. Dev Dyn 232, 526-8 (2005).10.1002/dvdy.20307

4. Keller, A. Drosophila melanogaster's history as a human commensal. Current Biology 17, R77-R81 (2007).DOI 10.1016/j.cub.2006.12.031

5. Markow, T.A. The secret lives of Drosophila flies. Elife 4(2015).10.7554/eLife.06793

6. Stephenson, R. & Metcalfe, N.H. Drosophila melanogaster: a fly through its history and current use. J R Coll Physicians Edinb 43, 70-5 (2013).10.4997/JRCPE.2013.116

7. Rubin, G.M. & Spradling, A.C. Genetic transformation of Drosophila with transposable element vectors. Science 218, 348-53 (1982).10.1126/science.6289436

8. Spradling, A.C. & Rubin, G.M. Transposition of cloned P elements into Drosophila germ line chromosomes. Science 218, 341-7 (1982).10.1126/science.6289435

9. Lachaise, D. et al. Historical Biogeography of the Drosophila-Melanogaster Species Subgroup. Evolutionary Biology-New York 22, 159-225 (1988).

10. Izumitani, H.F., Kusaka, Y., Koshikawa, S., Toda, M.J. & Katoh, T. Phylogeography of the Subgenus Drosophila (Diptera: Drosophilidae): Evolutionary History of Faunal Divergence between the Old and the New Worlds. PLoS One 11, e0160051 (2016).10.1371/journal.pone.0160051

11. Russo, C.A., Takezaki, N. & Nei, M. Molecular phylogeny and divergence times of drosophilid species. Mol Biol Evol 12, 391-404 (1995).10.1093/oxfordjournals.molbev.a040214

12. Mansourian, S. et al. Wild African Drosophila melanogaster Are Seasonal Specialists on Marula Fruit. Curr Biol 28, 3960-3968 e3 (2018).10.1016/j.cub.2018.10.033

13. Pool, J.E. et al. Population Genomics of sub-saharan Drosophila melanogaster: African diversity and non-African admixture. PLoS Genet 8, e1003080 (2012).10.1371/journal.pgen.1003080

14. Arguello, J.R., Laurent, S. & Clark, A.G. Demographic History of the Human Commensal Drosophila melanogaster. Genome Biol Evol 11, 844-854 (2019).10.1093/gbe/evz022

15. Haudry, A., Laurent, S. & Kapun, M. Population Genomics on the Fly: Recent Advances in Drosophila. Methods Mol Biol 2090, 357-396 (2020).10.1007/978-1-0716-0199-0_15

16. Lachaise, D. & Silvain, J.F. How two Afrotropical endemics made two cosmopolitan human commensals: the Drosophila melanogaster-D. simulans palaeogeographic riddle. Genetica 120, 17-39 (2004). 10.1023/b:gene.0000017627.27537.ef

17. Adrion, J.R., Hahn, M.W. & Cooper, B.S. Revisiting classic clines in Drosophila melanogaster in the age of genomics. Trends Genet 31, 434-44 (2015).10.1016/j.tig.2015.05.006

18. Fabian, D.K. et al. Spatially varying selection shapes life history clines among populations of Drosophila melanogaster from sub-Saharan Africa. J Evol Biol 28, 826-40 (2015).10.1111/jeb.12607

19. Mayekar, H.V. et al. Clinal variation as a tool to understand climate change. Front Physiol 13, 880728 (2022).10.3389/fphys.2022.880728

20. Rodrigues, M.F., Vibranovski, M.D. & Cogni, R. Clinal and seasonal changes are correlated in Drosophila melanogaster natural populations. Evolution 75, 2042-2054 (2021).10.1111/evo.14300

21. Machado, H.E. et al. Broad geographic sampling reveals the shared basis and environmental correlates of seasonal adaptation in Drosophila. Elife 10(2021).10.7554/eLife.67577

22. Bennie, J.J., Duffy, J.P., Inger, R. & Gaston, K.J. Biogeography of time partitioning in mammals. Proc Natl Acad Sci U S A 111, 13727-32 (2014).10.1073/pnas.1216063110

23. Daan, S. Adaptive daily strategies in behavior. in Biological rhythms 275-298 (Springer, 1981).

24. Cederroth, C.R. et al. Medicine in the Fourth Dimension. Cell Metab 30, 238-250 (2019).10.1016/j.cmet.2019.06.019

25. Koronowski, K.B. & Sassone-Corsi, P. Communicating clocks shape circadian homeostasis. Science 371(2021).10.1126/science.abd0951

26. Takahashi, J.S. Transcriptional architecture of the mammalian circadian clock. Nat Rev Genet 18, 164-179 (2017).10.1038/nrg.2016.150

27. Young, M.W. & Kay, S.A. Time zones: a comparative genetics of circadian clocks. Nat Rev Genet 2, 702-15 (2001).10.1038/35088576

28. Keene, A.C. & Duboue, E.R. The origins and evolution of sleep. J Exp Biol 221(2018).10.1242/jeb.159533

29. Sehgal, A. & Mignot, E. Genetics of sleep and sleep disorders. Cell 146, 194-207 (2011).10.1016/j.cell.2011.07.004

30. Shafer, O.T. & Keene, A.C. The Regulation of Drosophila Sleep. Curr Biol 31, R38-R49 (2021).10.1016/j.cub.2020.10.082

31. Beckwith, E.J. & French, A.S. Sleep in Drosophila and Its Context. Front Physiol 10, 1167 (2019).10.3389/fphys.2019.01167

32. Harding, E.C., Franks, N.P. & Wisden, W. The Temperature Dependence of Sleep. Front Neurosci 13, 336 (2019).10.3389/fnins.2019.00336

33. Mattingly, S.M. et al. The effects of seasons and weather on sleep patterns measured through longitudinal multimodal sensing. NPJ Digit Med 4, 76 (2021).10.1038/s41746-021-00435-2

34. Obradovich, N., Migliorini, R., Mednick, S.C. & Fowler, J.H. Nighttime temperature and human sleep loss in a changing climate. Sci Adv 3, e1601555 (2017).10.1126/sciadv.1601555

35. Okamoto-Mizuno, K. & Mizuno, K. Effects of thermal environment on sleep and circadian rhythm. J Physiol Anthropol 31, 14 (2012).10.1186/1880-6805-31-14

36. Heckrotte, C. The effect of the environmental factors in the locomotory activity of the plains garter snake (Thamnophis radix radix). Animal Behaviour 10, 193-207 (1962).

37. Sweeney, B.M. & Hastings, J.W. Effects of temperature upon diurnal rhythms. Cold Spring Harb Symp Quant Biol 25, 87-104 (1960).10.1101/sqb.1960.025.01.009

38. Yetish, G. et al. Natural sleep and its seasonal variations in three pre-industrial societies. Curr Biol 25, 2862-2868 (2015).10.1016/j.cub.2015.09.046

39. Alpert, M.H., Gil, H., Para, A. & Gallio, M. A thermometer circuit for hot temperature adjusts Drosophila behavior to persistent heat. Curr Biol 32, 4079-4087 e4 (2022).10.1016/j.cub.2022.07.060

40. Cao, W. & Edery, I. A novel pathway for sensory-mediated arousal involves splicing of an intron in the period clock gene. Sleep 38, 41-51 (2015).10.5665/sleep.4322

41. Majercak, J., Sidote, D., Hardin, P.E. & Edery, I. How a circadian clock adapts to seasonal decreases in temperature and day length. Neuron 24, 219-30 (1999).10.1016/s0896-6273(00)80834-x

42. Parisky, K.M., Agosto Rivera, J.L., Donelson, N.C., Kotecha, S. & Griffith, L.C. Reorganization of Sleep by Temperature in Drosophila Requires Light, the Homeostat, and the Circadian Clock. Curr Biol 26, 882-92 (2016).10.1016/j.cub.2016.02.011

43. Lehrskov, L.L. et al. The role of IL-1 in postprandial fatigue. Mol Metab 12, 107-112 (2018).10.1016/j.molmet.2018.04.001

44. Monk, T.H. The post-lunch dip in performance. Clin Sports Med 24, e15-23, xi-xii (2005).10.1016/j.csm.2004.12.002

45. Murphy, K.R. et al. Postprandial sleep mechanics in Drosophila. Elife 5(2016).10.7554/eLife.19334

46. Borbely, A.A. A two process model of sleep regulation. Hum Neurobiol 1, 195-204 (1982).

47. Deboer, T. Sleep homeostasis and the circadian clock: Do the circadian pacemaker and the sleep homeostat influence each other's functioning? Neurobiol Sleep Circadian Rhythms 5, 68-77 (2018).10.1016/j.nbscr.2018.02.003

48. Mantua, J. & Spencer, R.M.C. Exploring the nap paradox: are mid-day sleep bouts a friend or foe? Sleep Med 37, 88-97 (2017).10.1016/j.sleep.2017.01.019

49. Panossian, L.A. & Veasey, S.C. Daytime sleepiness in obesity: mechanisms beyond obstructive sleep apnea--a review. Sleep 35, 605-15 (2012).10.5665/sleep.1812

50. Schapira, A.H. Excessive daytime sleepiness in Parkinson's disease. Neurology 63, S24-7 (2004).10.1212/wnl.63.8_suppl_3.s24

51. Most, E.I., Scheltens, P. & Van Someren, E.J. Increased skin temperature in Alzheimer's disease is associated with sleepiness. J Neural Transm (Vienna) 119, 1185-94 (2012).10.1007/s00702-012-0864-1

52. Te Lindert, B.H.W. & Van Someren, E.J.W. Skin temperature, sleep, and vigilance. Handb Clin Neurol 156, 353-365 (2018).10.1016/B978-0-444-63912-7.00021-7

53. Lane, J.M. et al. Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits. Nat Genet 49, 274-281 (2017).10.1038/ng.3749

54. Lane, J.M. et al. Genetics of circadian rhythms and sleep in human health and disease. Nat Rev Genet 24, 4-20 (2023).10.1038/s41576-022-00519-z

55. Lopez-Minguez, J., Morosoli, J.J., Madrid, J.A., Garaulet, M. & Ordonana, J.R. Heritability of siesta and night-time sleep as continuously assessed by a circadian-related integrated measure. Sci Rep 7, 12340 (2017).10.1038/s41598-017-12460-x

56. Ishimoto, H., Lark, A. & Kitamoto, T. Factors that Differentially Affect Daytime and Nighttime Sleep in Drosophila melanogaster. Front Neurol 3, 24 (2012).10.3389/fneur.2012.00024

57. Chiu, J.C., Low, K.H., Pike, D.H., Yildirim, E. & Edery, I. Assaying locomotor activity to study circadian rhythms and sleep parameters in Drosophila. J Vis Exp (2010).10.3791/2157

58. Garbe, D.S. et al. Context-specific comparison of sleep acquisition systems in Drosophila. Biol Open 4, 1558-68 (2015).10.1242/bio.013011

59. Gilestro, G.F. Video tracking and analysis of sleep in Drosophila melanogaster. Nat Protoc 7, 995-1007 (2012).10.1038/nprot.2012.041

60. Siwicki, K.K., Hardin, P.E. & Price, J.L. Reflections on contributing to "big discoveries" about the fly clock: Our fortunate paths as post-docs with 2017 Nobel laureates Jeff Hall, Michael Rosbash, and Mike Young. Neurobiol Sleep Circadian Rhythms 5, 58-67 (2018).10.1016/j.nbscr.2018.02.004

61. Wheeler, D.A., Hamblen-Coyle, M.J., Dushay, M.S. & Hall, J.C. Behavior in light-dark cycles of Drosophila mutants that are arrhythmic, blind, or both. J Biol Rhythms 8, 67-94 (1993).10.1177/074873049300800106

62. Matsumoto, A., Matsumoto, N., Harui, Y., Sakamoto, M. & Tomioka, K. Light and temperature cooperate to regulate the circadian locomotor rhythm of wild type and period mutants of Drosophila melanogaster. J Insect Physiol 44, 587-596 (1998).10.1016/s0022-1910(98)00046-8

63. Edery, I., Zwiebel, L.J., Dembinska, M.E. & Rosbash, M. Temporal phosphorylation of the Drosophila period protein. Proc Natl Acad Sci U S A 91, 2260-4
(1994).10.1073/pnas.91.6.2260

64. Hardin, P.E., Hall, J.C. & Rosbash, M. Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature 343, 536-40 (1990).10.1038/343536a0

65. Konopka, R.J. & Benzer, S. Clock mutants of Drosophila melanogaster. Proc Natl Acad Sci U S A 68, 2112-6
(1971).10.1073/pnas.68.9.2112

66. Hahn, M.W., Han, M.V. & Han, S.G. Gene family evolution across 12 Drosophila genomes. PLoS Genet 3, e197 (2007).10.1371/journal.pgen.0030197

67. Low, K.H., Lim, C., Ko, H.W. & Edery, I. Natural variation in the splice site strength of a clock gene and species-specific thermal adaptation. Neuron 60, 1054-67 (2008).10.1016/j.neuron.2008.10.048

68. Malard, F., Mackereth, C.D. & Campagne, S. Principles and correction of 5'-splice site selection. RNA Biol 19, 943-960 (2022).10.1080/15476286.2022.2100971

69. Roca, X., Krainer, A.R. & Eperon, I.C. Pick one, but be quick: 5' splice sites and the problems of too many choices. Genes Dev 27, 129-44 (2013).10.1101/gad.209759.112

70. Rosbash, M. & Seraphin, B. Who's on first? The U1 snRNP-5' splice site interaction and splicing. Trends Biochem Sci 16, 187-90 (1991).10.1016/0968-0004(91)90073-5

71. Lim, L.P. & Burge, C.B. A computational analysis of sequence features involved in recognition of short introns. Proc Natl Acad Sci U S A 98, 11193-8
(2001).10.1073/pnas.201407298

72. Mount, S.M. et al. Splicing signals in Drosophila: intron size, information content, and consensus sequences. Nucleic Acids Res 20, 4255-62 (1992).10.1093/nar/20.16.4255

73. Lachaise, D. et al. Evolutionary novelties in islands: Drosophila santomea, a new melanogaster sister species from Sao Tome. Proc Biol Sci 267, 1487-95 (2000).10.1098/rspb.2000.1169

74. Matute, D.R., Novak, C.J. & Coyne, J.A. Temperature-based extrinsic reproductive isolation in two species of Drosophila. Evolution 63, 595-612 (2009).10.1111/j.1558-5646.2008.00588.x

75. Turissini, D.A., Liu, G., David, J.R. & Matute, D.R. The evolution of reproductive isolation in the Drosophila yakuba complex of species. J Evol Biol 28, 557-75 (2015).10.1111/jeb.12588

76. Hamada, F.N. et al. An internal thermal sensor controlling temperature preference in Drosophila. Nature 454, 217-20 (2008).10.1038/nature07001

77. Ainsworth, J.R., Rossi, L.M. & Murphy, E.C., Jr. The Moloney murine sarcoma virus ts110 5' splice site signal contributes to the regulation of splicing efficiency and thermosensitivity. J Virol 70, 6474-8 (1996).10.1128/JVI.70.9.6474-6478.1996

78. Cizdziel, P.E., de Mars, M. & Murphy, E.C., Jr. Exploitation of a thermosensitive splicing event to study pre-mRNA splicing in vivo. Mol Cell Biol 8, 1558-69 (1988).10.1128/mcb.8.4.1558-1569.1988

79. Touchman, J.W. et al. Branchpoint and polypyrimidine tract mutations mediating the loss and partial recovery of the Moloney murine sarcoma virus MuSVts110 thermosensitive splicing phenotype. J Virol 69, 7724-33 (1995).10.1128/JVI.69.12.7724-7733.1995

80. Anna, A. & Monika, G. Splicing mutations in human genetic disorders: examples, detection, and confirmation. J Appl Genet 59, 253-268 (2018).10.1007/s13353-018-0444-7

81. Daguenet, E., Dujardin, G. & Valcarcel, J. The pathogenicity of splicing defects: mechanistic insights into pre-mRNA processing inform novel therapeutic approaches. EMBO Rep 16, 1640-55 (2015).10.15252/embr.201541116

82. Jung, H., Lee, K.S. & Choi, J.K. Comprehensive characterisation of intronic mis-splicing mutations in human cancers. Oncogene 40, 1347-1361 (2021).10.1038/s41388-020-01614-3

83. Scotti, M.M. & Swanson, M.S. RNA mis-splicing in disease. Nat Rev Genet 17, 19-32 (2016).10.1038/nrg.2015.3

84. Carmel, I., Tal, S., Vig, I. & Ast, G. Comparative analysis detects dependencies among the 5' splice-site positions. RNA 10, 828-40 (2004).10.1261/rna.5196404

85. Weil, D. et al. Temperature-dependent expression of a collagen splicing defect in the fibroblasts of a patient with Ehlers-Danlos syndrome type VII. J Biol Chem 264, 16804-9 (1989).

86. Ibrahim, E.C. et al. Weak definition of IKBKAP exon 20 leads to aberrant splicing in familial dysautonomia. Hum Mutat 28, 41-53 (2007).10.1002/humu.20401

87. Lloyd, J., Narcisi, P., Richards, A. & Pope, F.M. A T+6 to C+6 mutation in the donor splice site of COL3A1 IVS7 causes exon skipping and results in Ehlers-Danlos syndrome type IV. J Med Genet 30, 376-80 (1993).10.1136/jmg.30.5.376

88. Suzuki, H. et al. Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma. Nature 574, 707-711 (2019).10.1038/s41586-019-1650-0

89. Hibio, N., Hino, K., Shimizu, E., Nagata, Y. & Ui-Tei, K. Stability of miRNA 5'terminal and seed regions is correlated with experimentally observed miRNA-mediated silencing efficacy. Sci Rep 2, 996 (2012).10.1038/srep00996

90. Rajpurohit, S., Zhao, X. & Schmidt, P.S. A resource on latitudinal and altitudinal clines of ecologically relevant phenotypes of the Indian Drosophila. Sci Data 4, 170066 (2017).10.1038/sdata.2017.66

91. Low, K.H., Chen, W.F., Yildirim, E. & Edery, I. Natural variation in the Drosophila melanogaster clock gene period modulates splicing of its 3'-terminal intron and mid-day siesta. PLoS One 7, e49536 (2012).10.1371/journal.pone.0049536

92. Zhang, Z., Cao, W. & Edery, I. The SR protein B52/SRp55 regulates splicing of the period thermosensitive intron and mid-day siesta in Drosophila. Sci Rep 8, 1872 (2018).10.1038/s41598-017-18167-3

93. Preussner, M. et al. Body Temperature Cycles Control Rhythmic Alternative Splicing in Mammals. Mol Cell 67, 433-446 e4 (2017).10.1016/j.molcel.2017.06.006

94. Cao, W. & Edery, I. Mid-day siesta in natural populations of D. melanogaster from Africa exhibits an altitudinal cline and is regulated by splicing of a thermosensitive intron in the period clock gene. BMC Evol Biol 17, 32 (2017).10.1186/s12862-017-0880-8

95. Yang, Y. & Edery, I. Parallel clinal variation in the mid-day siesta of Drosophila melanogaster implicates continent-specific targets of natural selection. PLoS Genet 14, e1007612 (2018).10.1371/journal.pgen.1007612

96. Hoffmann, A.A. & Weeks, A.R. Climatic selection on genes and traits after a 100 year-old invasion: a critical look at the temperate-tropical clines in Drosophila melanogaster from eastern Australia. Genetica 129, 133-47 (2007).10.1007/s10709-006-9010-z

97. Kolaczkowski, B., Kern, A.D., Holloway, A.K. & Begun, D.J. Genomic differentiation between temperate and tropical Australian populations of Drosophila melanogaster. Genetics 187, 245-60 (2011).10.1534/genetics.110.123059

98. Brown, E.B. et al. Variation in sleep and metabolic function is associated with latitude and average temperature in Drosophila melanogaster. Ecol Evol 8, 4084-4097 (2018).10.1002/ece3.3963

99. Svetec, N., Zhao, L., Saelao, P., Chiu, J.C. & Begun, D.J. Evidence that natural selection maintains genetic variation for sleep in Drosophila melanogaster. BMC Evol Biol 15, 41 (2015).10.1186/s12862-015-0316-2

100. Marrus, S.B., Zeng, H. & Rosbash, M. Effect of constant light and circadian entrainment of perS flies: evidence for light-mediated delay of the negative feedback loop in Drosophila. EMBO J 15, 6877-86 (1996).

101. Yang, Y. & Edery, I. Daywake, an Anti-siesta Gene Linked to a Splicing-Based Thermostat from an Adjoining Clock Gene. Curr Biol 29, 1728-1734 e4 (2019).10.1016/j.cub.2019.04.039

102. Alva, V. & Lupas, A.N. The TULIP superfamily of eukaryotic lipid-binding proteins as a mediator of lipid sensing and transport. Biochim Biophys Acta 1861, 913-923 (2016).10.1016/j.bbalip.2016.01.016

103. Cheng, Y., Gvakharia, B. & Hardin, P.E. Two alternatively spliced transcripts from the Drosophila period gene rescue rhythms having different molecular and behavioral characteristics. Mol Cell Biol 18, 6505-14 (1998).10.1128/MCB.18.11.6505.