title: The Burmese python genome reveals the molecular basis for extreme adaptation in snakes.
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.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Castoe
authors.forename: A P Jason
authors.initials: AP
authors.lastname: de Koning
authors.forename: Kathryn T
authors.initials: KT
authors.lastname: Hall
authors.forename: Daren C
authors.initials: DC
authors.lastname: Card
authors.forename: Drew R
authors.initials: DR
authors.lastname: Schield
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Fujita
authors.forename: Robert P
authors.initials: RP
authors.lastname: Ruggiero
authors.forename: Jack F
authors.initials: JF
authors.lastname: Degner
authors.forename: Juan M
authors.initials: JM
authors.lastname: Daza
authors.forename: Wanjun
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authors.lastname: Gu
authors.forename: Jacobo
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authors.lastname: Reyes-Velasco
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Shaney
authors.forename: Jill M
authors.initials: JM
authors.lastname: Castoe
authors.forename: Samuel E
authors.initials: SE
authors.lastname: Fox
authors.forename: Alex W
authors.initials: AW
authors.lastname: Poole
authors.forename: Daniel
authors.initials: D
authors.lastname: Polanco
authors.forename: Jason
authors.initials: J
authors.lastname: Dobry
authors.forename: Michael W
authors.initials: MW
authors.lastname: Vandewege
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Schott
authors.forename: Aurélie
authors.initials: A
authors.lastname: Kapusta
authors.forename: Patrick
authors.initials: P
authors.lastname: Minx
authors.forename: Cédric
authors.initials: C
authors.lastname: Feschotte
authors.forename: Peter
authors.initials: P
authors.lastname: Uetz
authors.forename: David A
authors.initials: DA
authors.lastname: Ray
authors.forename: Federico G
authors.initials: FG
authors.lastname: Hoffmann
authors.forename: Robert
authors.initials: R
authors.lastname: Bogden
authors.forename: Eric N
authors.initials: EN
authors.lastname: Smith
authors.forename: Belinda S W
authors.initials: BS
authors.lastname: Chang
authors.forename: Freek J
authors.initials: FJ
authors.lastname: Vonk
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Casewell
authors.forename: Christiaan V
authors.initials: CV
authors.lastname: Henkel
authors.forename: Michael K
authors.initials: MK
authors.lastname: Richardson
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Mackessy
authors.forename: Anne M
authors.initials: AM
authors.lastname: Bronikowski
authors.forename: Anne M
authors.initials: AM
authors.lastname: Bronikowsi
authors.forename: Mark
authors.initials: M
authors.lastname: Yandell
authors.forename: Wesley C
authors.initials: WC
authors.lastname: Warren
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Secor
authors.forename: David D
authors.initials: DD
authors.lastname: Pollock
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D017821:Boidae / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000502:physiology*; D016678:Genome / Q000502:physiology*; D006801:Humans; D009928:Organ Specificity / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*
keywords: comparative genomics; physiological remodeling; systems biology; transcriptomics; transposable elements