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Generalization and Discovery by Assuming Conserved Mechanisms: Cross-Species Research on Circadian Oscillators

Published online by Cambridge University Press:  01 January 2022

William Bechtel
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Abstract

In many domains of biology, explanation takes the form of characterizing the mechanism responsible for a particular phenomenon in a specific biological system. How are such explanations generalized? One important strategy assumes conservation of mechanisms through evolutionary descent. But conservation is seldom complete. In the case discussed, the central mechanism for circadian rhythms in animals was first identified in Drosophila and then extended to mammals. Scientists' working assumption that the clock mechanisms would be conserved both yielded important generalizations and served as a heuristic for discovery, especially when significant differences between the insect and mammalian mechanism were identified.

Type
Research Article
Information
Philosophy of Science , Volume 76 , Issue 5 , December 2009 , pp. 762 - 773
Copyright
Copyright © The Philosophy of Science Association

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Footnotes

‡

I thank Adele Abrahamsen, Lindley Darden, and members of the University of California, San Diego, Philosophy of Biology Research Group and of the DC History and Philosophy of Biology Discussion Group for very helpful comments and suggestions.

References

Albrecht, Urs (2002), “Functional Genomics of Sleep and Circadian Rhythm: Invited Review; Regulation of Mammalian Circadian Clock Genes”, Functional Genomics of Sleep and Circadian Rhythm: Invited Review; Regulation of Mammalian Circadian Clock Genes 92:1348–1355.Google Scholar
Albrecht, Urs, Sun, Zhong Sheng, Eichele, Gregor, and Lee, Cheng Chi (1997), “A Differential Response of Two Putative Mammalian Circadian Regulators, mper1 and mper2, to Light”, A Differential Response of Two Putative Mammalian Circadian Regulators, mper1 and mper2, to Light 91:1055–1064.Google Scholar
Barnes, Jessica W., Tischkau, Shelley A., Barnes, Jeffrey A., Mitchell, Jennifer W., Burgoon, Penny W., Hickok, Jason R., and Gillette, Martha U. (2003), “Requirement of Mammalian Timeless for Circadian Rhythmicity”, Requirement of Mammalian Timeless for Circadian Rhythmicity 302:439–442.Google ScholarPubMed
Bechtel, William (2006), Discovering Cell Mechanisms: The Creation of Modern Cell Biology. Cambridge: Cambridge University Press.Google Scholar
Bechtel, William, and Abrahamsen, Adele (2005), “Explanation: A Mechanist Alternative”, Explanation: A Mechanist Alternative 36:421–441.Google ScholarPubMed
Bechtel, William, and Richardson, Robert C. (1993), Discovering Complexity: Decomposition and Localization as Strategies in Scientific Research. Princeton, NJ: Princeton University Press.Google Scholar
Craver, Carl (2007), Explaining the Brain: What a Science of the Mind-Brain Could Be. New York: Oxford University Press.CrossRefGoogle Scholar
Darden, Lindley (2006), Reasoning in Biological Discoveries: Essays on Mechanisms, Interfield Relations, and Anomaly Resolution. Cambridge: Cambridge University Press.CrossRefGoogle Scholar
Darden, Lindley, and Craver, Carl (2002), “Strategies in the Interfield Discovery of the Mechanism of Protein Synthesis”, Strategies in the Interfield Discovery of the Mechanism of Protein Synthesis 33:1–28.Google Scholar
Darlington, Thomas K., Wager-Smith, Karen, Ceriani, M. Fernanda, Staknis, David, Gekakis, Nicholas, Steeves, Thomas D., Weitz, Charles J., Takahashi, Joseph S., and Kay, Steve A. (1998), “Closing the Circadian Loop: Clock-Induced Transcription of Its Own Inhibitors per and tim”, Closing the Circadian Loop: Clock-Induced Transcription of Its Own Inhibitors per and tim 280:1599–1603.Google ScholarPubMed
Emery, Patrick T., So, W. V., Kanedo, M., Hall, J. C., and Rosbash, Michael (1998), “CRY, a Drosophila Clock and Light-Regulated Cryptochrome, Is a Major Contributor to Circadian Rhythm Resetting and Photosensitivity”, CRY, a Drosophila Clock and Light-Regulated Cryptochrome, Is a Major Contributor to Circadian Rhythm Resetting and Photosensitivity 95:669–679.Google ScholarPubMed
Gekakis, Nicholas, Saez, Lino, Delahaye-Brown, Anne-Marie, Myers, Michael P., Sehgal, Amita, Young, Michael W., and Weitz, Charles J. (1995), “Isolation of timeless by PER Protein Interaction: Defective Interaction between timeless Protein and Long-Period Mutant PERL”, Isolation of timeless by PER Protein Interaction: Defective Interaction between timeless Protein and Long-Period Mutant PERL 270:811–815.Google ScholarPubMed
Gekakis, Nicholas, Staknis, David, Nguyen, Hubert B., Davis, Fred C., Wilsbacher, Lisa D., King, David P., Takahashi, Joseph S., and Weitz, Charles J. (1998), “Role of the Clock Protein in the Mammalian Circadian Mechanism”, Role of the Clock Protein in the Mammalian Circadian Mechanism 280:1564–1569.Google ScholarPubMed
Griffin, Edmund A. Jr., Staknis, David, and Weitz, Charles J. (1999), “Light-Independent Role of CRY1 and CRY2 in the Mammalian Circadian Clock”, Light-Independent Role of CRY1 and CRY2 in the Mammalian Circadian Clock 286:768–771.Google ScholarPubMed
Hannibal, Jens (2002), “Neurotransmitters of the Retino-Hypothalamic Tract”, Neurotransmitters of the Retino-Hypothalamic Tract 309:73–88.Google ScholarPubMed
Hao, H., Allen, D. L., and Hardin, Paul E. (1997), “A Circadian Enhancer Mediates PER-Dependent mRNA Cycling in Drosophila Me la no gaster”, A Circadian Enhancer Mediates PER-Dependent mRNA Cycling in Drosophila Me la no gaster 17:3687–3693.Google ScholarPubMed
Hardin, Paul E., Hall, Jeffrey C., and Rosbash, Michael (1990), “Feedback of the Drosophila period Gene Product on Circadian Cycling of Its Messenger RNA Levels”, Feedback of the Drosophila period Gene Product on Circadian Cycling of Its Messenger RNA Levels 343:536–540.Google ScholarPubMed
Hattar, Samer, Lucas, Robert J., Mrosovsky, N., Thompson, S., Douglas, R. H., Hankins, Mark W., Lem, J., Biel, M., Hofmann, F., Foster, Russell G., and Yau, King-Wai (2003), “Melanopsin and Rod-Cone Photoreceptive Systems Account for All Major Accessory Visual Functions in Mice”, Melanopsin and Rod-Cone Photoreceptive Systems Account for All Major Accessory Visual Functions in Mice 424:75–81.Google ScholarPubMed
King, David P., Zhao, Yaliang, Sangoram, Ashvin M., Wilsbacher, Lisa D., Tanaka, Minoru, Antoch, Marina P., Steeves, Thomas D. L., Vitaterna, Martha Hotz, Kornhauser, Jon M., Lowrey, Phillip L., Turek, Fred W., and Takahashi, Joseph S. (1997), “Positional Cloning of the Mouse Circadian Clock Gene”, Positional Cloning of the Mouse Circadian Clock Gene 89:641–653.Google ScholarPubMed
Konopka, Ronald J., and Benzer, Seymour (1971), “Clock Mutants of Drosophila Me la no gaster”, Clock Mutants of Drosophila Me la no gaster 89:2112–2116.Google Scholar
Machamer, Peter, Darden, Lindley, and Craver, Carl (2000), “Thinking about Mechanisms”, Thinking about Mechanisms 67:1–25.Google Scholar
Miyamoto, Yasuhide, and Sancar, Aziz (1998), “Vitamin B2-Based Blue-Light Photoreceptors in the Retinohypothalamic Tract as the Photoactive Pigments for Setting the Circadian Clock in Mammals”, Vitamin B2-Based Blue-Light Photoreceptors in the Retinohypothalamic Tract as the Photoactive Pigments for Setting the Circadian Clock in Mammals 95:6097–6102.Google ScholarPubMed
Pittendrigh, Colin S. (1954), “On Temperature Independence in the Clock-System Controlling Emergence Time in Drosophila”, On Temperature Independence in the Clock-System Controlling Emergence Time in Drosophila 40:1018–1029.Google ScholarPubMed
Provencio, Ignacio, Jiang, Guisen, De Grip, Willem J., Hayes, William Par, and Rollag, Mark D. (1998), “Melanopsin: An Opsin in Melanophores, Brain, and Eye”, Melanopsin: An Opsin in Melanophores, Brain, and Eye 95:340–345.Google Scholar
Provencio, Ignacio, Rodriguez, Ignacio R., Jiang, Guisen, Hayes, William Par, Moreira, Ernesto F., and Rollag, Mark D. (2000), “A Novel Human Opsin in the Inner Retina”, A Novel Human Opsin in the Inner Retina 20:600–605.Google ScholarPubMed
Ruby, Norman F., Brennan, Thomas J., Xie, Xinmin, Cao, Vinh, Franken, Paul, Heller, H. Craig, and O’Hara, Bruce F. (2002), “Role of Melanopsin in Circadian Responses to Light”, Role of Melanopsin in Circadian Responses to Light 298:2211–2213.Google Scholar
Saez, Lino, and Young, Michael W. (1996), “Regulation of Nuclear Entry of the Drosophila-Clock Proteins Period and Timeless”, Regulation of Nuclear Entry of the Drosophila-Clock Proteins Period and Timeless 17:979–990.Google ScholarPubMed
Sangoram, Ashvin M., Saez, Lino, Antoch, Marina P., Gekakis, Nicholas, Staknis, David, Whiteley, Andrew, Fruechte, Ethan M., Vitaterna, Martha Hotz, Shimomura, Kazuhiro, King, David P., Young, Michael W., Weitz, Charles J., and Takahashi, Joseph S. (1998), “Mammalian Circadian Autoregulatory Loop: A Timeless Ortholog and Mper1 Interact and Negatively Regulate CLOCK-BMAL1-Induced Transcription”, Mammalian Circadian Autoregulatory Loop: A Timeless Ortholog and Mper1 Interact and Negatively Regulate CLOCK-BMAL1-Induced Transcription 21:1101–1113.Google ScholarPubMed
Sehgal, Amita, Price, Jeffrey L., Man, Bernice, and Young, Michael W. (1994), “Loss of Circadian Behavioral Rhythms and per RNA Oscillations in the Drosophila Mutant timeless”, Loss of Circadian Behavioral Rhythms and per RNA Oscillations in the Drosophila Mutant timeless 263:1603–1606.Google ScholarPubMed
Stanewsky, Ralf, Kaneko, Maki, Emery, Patrick, Beretta, Bonnie, Wager-Smith, Karen, Kay, Steve A., Rosbash, Michael, and Hall, Jeffrey C. (1998), “The cry b Mutation Identifies Cryptochrome as a Circadian Photoreceptor in Drosophila”, The cry b Mutation Identifies Cryptochrome as a Circadian Photoreceptor in Drosophila 95:681–692.Google ScholarPubMed
Sun, Zhong Sheng, Albrecht, Urs, Zhuchenko, Olga, Bailey, Jennifer, Eichele, Gregor, and Lee, Cheng Chi (1997), “RIGUI, a Putative Mammalian Ortholog of the Drosophila period Gene”, RIGUI, a Putative Mammalian Ortholog of the Drosophila period Gene 90:1003–1011.Google ScholarPubMed
Tei, Hajime, Okamura, Hitoshi, Shigeyoshi, Yasufumi, Fukuhara, Chiaki, Ozawa, Ritsuko, Hirose, Matsumi, and Sakaki, Yoshiyuki (1997), “Circadian Oscillation of a Mammalian Homologue of the Drosophila period Gene”, Circadian Oscillation of a Mammalian Homologue of the Drosophila period Gene 389:512–516.Google ScholarPubMed
Thresher, Randy J., Vitaterna, Martha Hotz, Miyamoto, Yasuhide, Kazantsev, Aleksey, Hsu, David S., Petit, Claude, Selby, Christopher P., Dawut, Lale, Smithies, Oliver, Takahashi, Joseph S., and Sancar, Aziz (1998), “Role of Mouse Cryptochrome Blue-Light Photoreceptor in Circadian Photoresponses”, Role of Mouse Cryptochrome Blue-Light Photoreceptor in Circadian Photoresponses 282:1490–1494.Google ScholarPubMed
Todo, Takeshi, Ryo, Haruko, Yamamoto, Kazuo, Toh, Hiroyuki, Inui, Taiichiro, Ayaki, Hitoshi, Nomura, Taisei, and Ikenaga, Mituo (1996), “Similarity among the Drosophila (6-4) Photolyase, a Human Photolyase Homolog, and the DNA Photolyase-Blue-Light Photoreceptor Family”, Similarity among the Drosophila (6-4) Photolyase, a Human Photolyase Homolog, and the DNA Photolyase-Blue-Light Photoreceptor Family 272:109–112.Google ScholarPubMed
van der Horst, Gijsbertus T. J., Muijtjens, Manja, Kobayashi, Kumiko, Takano, Riya, Kanno, Shin-ichiro, Takao, Masashi, Wit, Jan de, Verkerk, Anton, Eker, Andre P. M., Leenen, Dik van, Buijs, Ruud, Bootsma, Dirk, Hoeijmakers, Jan H. J., and Yasui, Akira (1999), “Mammalian Cry1 and Cry2 Are Essential for Maintenance of Circadian Rhythms”, Mammalian Cry1 and Cry2 Are Essential for Maintenance of Circadian Rhythms 398:627–630.Google ScholarPubMed
Vitaterna, Martha Hotz, King, David P., Chang, Anne-Marie, Kornhauser, Jon M., Lowrey, Phillip L., McDonald, J. David, Dove, William F., Pinto, Lawrence H., Turek, Fred W., and Takahashi, Joseph S. (1994), “Mutagenesis and Mapping of a Mouse Gene, Clock, Essential for Circadian Behavior”, Mutagenesis and Mapping of a Mouse Gene, Clock, Essential for Circadian Behavior 264:719–725.Google ScholarPubMed
Vosshall, Leslie B., Price, Jeffrey L., Sehgal, Amita, Saez, Lino, and Young, Michael W. (1994), “Block in Nuclear Localization of period Protein by a Second Clock Mutation, timeless”, Block in Nuclear Localization of period Protein by a Second Clock Mutation, timeless 263:1606–1609.Google ScholarPubMed
Zylka, Mark J., Shearman, Lauren P., Weaver, David R., and Reppert, Steven M. (1998), “Three period Homologs in Mammals: Differential Light Responses in the Suprachiasmatic Circadian Clock and Oscillating Transcripts Outside of Brain”, Three period Homologs in Mammals: Differential Light Responses in the Suprachiasmatic Circadian Clock and Oscillating Transcripts Outside of Brain 20:1103–1110.Google ScholarPubMed