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Research Article

The Burmese python genome reveals the molecular basis for extreme adaptation in snakes

Todd A. Castoe, A. P. Jason de Koning, Kathryn T. Hall, Daren C. Card, Drew R. Schield, Matthew K. Fujita, Robert P. Ruggiero, Jack F. Degner, Juan M. Daza, Wanjun Gu, Jacobo Reyes-Velasco, Kyle J. Shaney, Jill M. Castoe, Samuel E. Fox, Alex W. Poole, Daniel Polanco, Jason Dobry, Michael W. Vandewege, Qing Li, Ryan K. Schott, Aurélie Kapusta, Patrick Minx, Cédric Feschotte, Peter Uetz, David A. Ray, Federico G. Hoffmann, Robert Bogden, Eric N. Smith, Belinda S. W. Chang, Freek J. Vonk, Nicholas R. Casewell, Christiaan V. Henkel, Michael K. Richardson, Stephen P. Mackessy, Anne M. Bronikowsi, Mark Yandell, Wesley C. Warren, Stephen M. Secor, and David D. Pollock
PNAS first published December 2, 2013; https://doi.org/10.1073/pnas.1314475110
Todd A. Castoe
aDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045;
bDepartment of Biology, University of Texas, Arlington, TX 76010;
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A. P. Jason de Koning
aDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045;
cDepartment of Biochemistry and Molecular Biology, University of Calgary and Alberta Children’s Hospital Research Institute for Child and Maternal Health, Calgary, AB, Canada T2N 4N1;
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Kathryn T. Hall
aDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045;
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Daren C. Card
bDepartment of Biology, University of Texas, Arlington, TX 76010;
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Drew R. Schield
bDepartment of Biology, University of Texas, Arlington, TX 76010;
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Matthew K. Fujita
bDepartment of Biology, University of Texas, Arlington, TX 76010;
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Robert P. Ruggiero
aDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045;
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Jack F. Degner
dDepartment of Human Genetics, University of Chicago, Chicago, IL 60637;
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Juan M. Daza
eInstituto de Biologia, Universidad de Antiochia, Medellin, Colombia 05001000;
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Wanjun Gu
fKey Laboratory of Child Development and Learning Science, Southeast University, Ministry of Education, Nanjing 210096, China;
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Jacobo Reyes-Velasco
bDepartment of Biology, University of Texas, Arlington, TX 76010;
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Kyle J. Shaney
bDepartment of Biology, University of Texas, Arlington, TX 76010;
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Jill M. Castoe
aDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045;
bDepartment of Biology, University of Texas, Arlington, TX 76010;
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Samuel E. Fox
gDepartment of Biology, Linfield College, McMinnville, OR 97128;
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Alex W. Poole
aDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045;
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Daniel Polanco
aDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045;
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Jason Dobry
hAmplicon Express, Pullman, WA 99163;
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Michael W. Vandewege
iDepartment of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762;
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Qing Li
jDepartment of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112;
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Ryan K. Schott
kDepartment of Ecology and Evolutionary Biology and Cell and Systems Biology, Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, ON, Canada M5S 3G5;
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Aurélie Kapusta
jDepartment of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112;
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Patrick Minx
lGenome Institute, Washington University School of Medicine, St. Louis, MO 63108;
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Cédric Feschotte
jDepartment of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112;
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Peter Uetz
mCenter for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, VA 23284;
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David A. Ray
iDepartment of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762;
nDepartment of Biological Sciences, Texas Tech University, Lubbock, TX 79409;
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Federico G. Hoffmann
iDepartment of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762;
nDepartment of Biological Sciences, Texas Tech University, Lubbock, TX 79409;
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Robert Bogden
hAmplicon Express, Pullman, WA 99163;
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Eric N. Smith
bDepartment of Biology, University of Texas, Arlington, TX 76010;
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Belinda S. W. Chang
kDepartment of Ecology and Evolutionary Biology and Cell and Systems Biology, Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, ON, Canada M5S 3G5;
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Freek J. Vonk
oNaturalis Biodiversity Center, 2333 CR, Leiden, The Netherlands;
pInstitute of Biology Leiden, Leiden University, Sylvius Laboratory, Sylviusweg 72, 2300 RA, Leiden, The Netherlands;
qMolecular Ecology and Evolution Group, School of Biological Sciences, Bangor University, Bangor LL57 2UW, United Kingdom;
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Nicholas R. Casewell
qMolecular Ecology and Evolution Group, School of Biological Sciences, Bangor University, Bangor LL57 2UW, United Kingdom;
rAlistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom;
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Christiaan V. Henkel
pInstitute of Biology Leiden, Leiden University, Sylvius Laboratory, Sylviusweg 72, 2300 RA, Leiden, The Netherlands;
sZF Screens, Bio Partner Center, 2333 CH, Leiden, The Netherlands;
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Michael K. Richardson
pInstitute of Biology Leiden, Leiden University, Sylvius Laboratory, Sylviusweg 72, 2300 RA, Leiden, The Netherlands;
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Stephen P. Mackessy
tSchool of Biological Sciences, University of Northern Colorado, Greeley, CO 80639;
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Anne M. Bronikowsi
uDepartment of Ecology, Evolution, and Organismal Biology, Iowa State University, Ames, IA 50011; and
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Mark Yandell
jDepartment of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112;
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Wesley C. Warren
lGenome Institute, Washington University School of Medicine, St. Louis, MO 63108;
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Stephen M. Secor
vDepartment of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487
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David D. Pollock
aDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045;
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  • For correspondence: david.pollock@ucdenver.edu
  1. Edited by David B. Wake, University of California, Berkeley, CA, and approved November 4, 2013 (received for review July 31, 2013)

This article has a Correction. Please see:

  • Correction for Castoe et al., The Burmese python genome reveals the molecular basis for extreme adaptation in snakes - January 15, 2014

See related content:

  • King cobra genome and snake venom evolution
    - Dec 02, 2013
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Significance

The molecular basis of morphological and physiological adaptations in snakes is largely unknown. Here, we study these phenotypes using the genome of the Burmese python (Python molurus bivittatus), a model for extreme phenotypic plasticity and metabolic adaptation. We discovered massive rapid changes in gene expression that coordinate major changes in organ size and function after feeding. Many significantly responsive genes are associated with metabolism, development, and mammalian diseases. A striking number of genes experienced positive selection in ancestral snakes. Such genes were related to metabolism, development, lungs, eyes, heart, kidney, and skeletal structure—all highly modified features in snakes. Snake phenotypic novelty seems to be driven by the system-wide coordination of protein adaptation, gene expression, and changes in genome structure.

Abstract

Snakes possess many extreme morphological and physiological adaptations. Identification of the molecular basis of these traits can provide novel understanding for vertebrate biology and medicine. Here, we study snake biology using the genome sequence of the Burmese python (Python molurus bivittatus), a model of extreme physiological and metabolic adaptation. We compare the python and king cobra genomes along with genomic samples from other snakes and perform transcriptome analysis to gain insights into the extreme phenotypes of the python. We discovered rapid and massive transcriptional responses in multiple organ systems that occur on feeding and coordinate major changes in organ size and function. Intriguingly, the homologs of these genes in humans are associated with metabolism, development, and pathology. We also found that many snake metabolic genes have undergone positive selection, which together with the rapid evolution of mitochondrial proteins, provides evidence for extensive adaptive redesign of snake metabolic pathways. Additional evidence for molecular adaptation and gene family expansions and contractions is associated with major physiological and phenotypic adaptations in snakes; genes involved are related to cell cycle, development, lungs, eyes, heart, intestine, and skeletal structure, including GRB2-associated binding protein 1, SSH, WNT16, and bone morphogenetic protein 7. Finally, changes in repetitive DNA content, guanine-cytosine isochore structure, and nucleotide substitution rates indicate major shifts in the structure and evolution of snake genomes compared with other amniotes. Phenotypic and physiological novelty in snakes seems to be driven by system-wide coordination of protein adaptation, gene expression, and changes in the structure of the genome.

  • comparative genomics
  • transposable elements
  • systems biology
  • transcriptomics
  • physiological remodeling

Footnotes

  • ↵1To whom correspondence should be addressed. E-mail: david.pollock{at}ucdenver.edu.
  • Author contributions: T.A.C. and D.D.P. designed research; T.A.C., A.P.J.d.K., K.T.H., D.C.C., D.R.S., M.K.F., R.P.R., J.F.D., J.M.D., W.G., J.R.-V., K.J.S., J.M.C., S.E.F., A.W.P., D.P., M.W.V., Q.L., R.K.S., A.K., P.M., P.U., E.N.S., B.S.W.C., F.J.V., N.R.C., C.V.H., M.K.R., S.P.M., M.Y., W.C.W., and S.M.S. performed research; T.A.C., J.D., P.M., R.B., E.N.S., A.M.B., W.C.W., S.M.S., and D.D.P. contributed new reagents/analytic tools; T.A.C., A.P.J.d.K., K.T.H., D.C.C., D.R.S., M.K.F., R.P.R., J.F.D., J.M.D., W.G., J.R.-V., K.J.S., S.E.F., M.W.V., Q.L., R.K.S., A.K., P.M., C.F., D.A.R., F.G.H., B.S.W.C., F.J.V., N.R.C., C.V.H., M.K.R., S.P.M., M.Y., W.C.W., S.M.S., and D.D.P. analyzed data; and T.A.C. and D.D.P. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AEQU00000000).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1314475110/-/DCSupplemental.

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Extreme adaptation seen in snake genomes
Todd A. Castoe, A. P. Jason de Koning, Kathryn T. Hall, Daren C. Card, Drew R. Schield, Matthew K. Fujita, Robert P. Ruggiero, Jack F. Degner, Juan M. Daza, Wanjun Gu, Jacobo Reyes-Velasco, Kyle J. Shaney, Jill M. Castoe, Samuel E. Fox, Alex W. Poole, Daniel Polanco, Jason Dobry, Michael W. Vandewege, Qing Li, Ryan K. Schott, Aurélie Kapusta, Patrick Minx, Cédric Feschotte, Peter Uetz, David A. Ray, Federico G. Hoffmann, Robert Bogden, Eric N. Smith, Belinda S. W. Chang, Freek J. Vonk, Nicholas R. Casewell, Christiaan V. Henkel, Michael K. Richardson, Stephen P. Mackessy, Anne M. Bronikowsi, Mark Yandell, Wesley C. Warren, Stephen M. Secor, David D. Pollock
Proceedings of the National Academy of Sciences Dec 2013, 201314475; DOI: 10.1073/pnas.1314475110

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Extreme adaptation seen in snake genomes
Todd A. Castoe, A. P. Jason de Koning, Kathryn T. Hall, Daren C. Card, Drew R. Schield, Matthew K. Fujita, Robert P. Ruggiero, Jack F. Degner, Juan M. Daza, Wanjun Gu, Jacobo Reyes-Velasco, Kyle J. Shaney, Jill M. Castoe, Samuel E. Fox, Alex W. Poole, Daniel Polanco, Jason Dobry, Michael W. Vandewege, Qing Li, Ryan K. Schott, Aurélie Kapusta, Patrick Minx, Cédric Feschotte, Peter Uetz, David A. Ray, Federico G. Hoffmann, Robert Bogden, Eric N. Smith, Belinda S. W. Chang, Freek J. Vonk, Nicholas R. Casewell, Christiaan V. Henkel, Michael K. Richardson, Stephen P. Mackessy, Anne M. Bronikowsi, Mark Yandell, Wesley C. Warren, Stephen M. Secor, David D. Pollock
Proceedings of the National Academy of Sciences Dec 2013, 201314475; DOI: 10.1073/pnas.1314475110
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