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The Burmese python's phenotype — or physical characteristics — represents
one of the most extreme examples of evolutionary adaptation.
By ramping up their metabolism, they can increase the mass of their
heart, liver, small intestine and kidneys 35 to 150 percent — in only 24 to 48 hours.
When digestion is completed, their organs return to their original size within a matter of days.
'Extreme adaptation' of Burmese python genome
A Burmese python's ability to ramp up its metabolism and enlarge its organs, swallow and digest prey whole, can be traced to an unusually rapid evolution of its genes.
Todd Castoe, assistant professor of biology, University of Texas at Arlington College of Science, lead author, along with 38 co-authors from four countries, have sequenced and analyzed the genome of the Burmese python, or Python molurus bivittatus.
The work is published (Dec. 2, 2013) in the Proceedings of the National Academy of Sciences along with a companion paper on the sequencing and analysis of the king cobra (Ophiophagus hannah). Together, both papers represent the first complete and annotated snake genomes.
Snakes contain many of the same genes as other vertebrates. Therefore, studying how their genes evolved to produce their extreme characteristics will help explain how their genes function, and how a snake's extreme feats of organ remodeling occur.
Such knowledge may be useful in treating human diseases.
"One of the fundamental questions of evolutionary biology is how vertebrates with all the same genes display such vastly different characteristics. The Burmese python is a great way to study this puzzle because it is so extreme," Todd Castoe.
Castoe began working on the python project as a postdoctoral fellow at the University of Colorado School of Medicine in the laboratory of associate professor and paper corresponding author, David D. Pollock.
Castoe: "We'd like to know how the snake uses genes, that all vertebrates posess, to do things that no other vertebrates can do."
The study calls into question previous theories that major obvious physical differences between species are primarily the result of changes in how genes are expressed — or turned on.
Instead, it sugests that protein adaptation, plus gene expression, and changes in the structure of the organization of the snake genome, altogether define the unusual characteristics of snakes.
Pollock believes the python and king cobra studies represent a significant addition to the field of "comparative systems genomics — an analysis of evolution in multiple vertebrate genomes — to understand how entire systems of interacting genes evolve from molecules."
The Burmese python's phenotype — or physical characteristics — represents one of the most extreme examples of evolutionary adaptation.
Like all snakes, its evolutionary origin included reduction in function of one lung and elongating its mid-section, skeleton and organs. It also has an extraordinary ability for what researchers call "physiological remodeling."
Physiological remodeling refers to the process by which pythons digest meals much larger than their size, such as chickens or piglets. They ramp up their metabolism — increasing the mass of their heart, liver, small intestine and kidneys 35 to 150 percent — in only 24 to 48 hours.
When digestion is complete, their organs return to their original size within a matter of days.
The authors suggest that understanding how snakes accomplish this tremendous feat could hold vital clues to developing treatments for many human diseases.
"The Burmese python has an amazing physiology. With its genome in hand, we can now explore the python's many untapped molecular mechanisms which dramatically increase its metabolic rate, shut down acid production, improve intestinal function, and rapidly increase the size of its heart, intestine, pancreas, liver, and kidneys," said Stephen Secor, associate professor of biological sciences, University of Alabama, and a co-author on the paper.
"The benefits of these discoveries transfers to the treatment of metabolic disorders such as ulcers, intestinal malabsorption, Crohn's disease, cardiac hypertrophy and the loss of organ performance."
To complete their work, the team aligned 7,442 genes from the python and cobra, with genes of other species including: amphibians, reptiles, birds and mammals.
Using a statistical method called "branch site codon modeling," they looked for genes that had been positively selected — evolutionarily changed as a result of natural selection — in the python, the cobra, as well as in an early snake ancestor of both, and found hundreds of gene changes.
Analyses showed a remarkable correlation between the function of the selected genes, and the many unique functions of snake biology – such as their unique metabolism, spine and skull shape, and even their cell cycle regulation.
Gene sequences for comparison were made available from the Ensembl Genome Browser.
Many of the altered genes the team observed also have prominent medical significance.
The python genome showed some changes to the gene GAB1, which in human research plays a role in breast cancer, melanomas and childhood leukemia.
In addition to changes in individual genes and how those genes were expressed (or are turned on), researchers found that extreme characteristics in snakes could be linked to duplications, or losses, in multigene families. Some of those gene families include ancient losses, but more recent multigene families are linked to the python's high resolution vision and its' ability to detect chemical cues from the environment.
Researchers also note that while the current presumption is that reptile genes and genomes change at a very slow rate, they found that the snake genome evolves at one of the fastest rates of any vertebrate.
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.
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.
Todd A. Castoea,b, A. P. Jason de Koninga,c, Kathryn T. Halla, Daren C. Cardb, Drew R. Schieldb, Matthew K. Fujitab, Robert P. Ruggieroa, Jack F. Degnerd, Juan M. Dazae, Wanjun Guf, Jacobo Reyes-Velascob, Kyle J. Shaneyb, Jill M. Castoea,b, Samuel E. Foxg, Alex W. Poolea, Daniel Polancoa, Jason Dobryh, Michael W. Vandewegei, Qing Lij, Ryan K. Schottk, Aurélie Kapustaj, Patrick Minxl, Cédric Feschottej, Peter Uetzm, David A. Rayi,n, Federico G. Hoffmanni,n, Robert Bogdenh, Eric N. Smithb, Belinda S. W. Changk, Freek J. Vonko,p,q, Nicholas R. Casewellq,r, Christiaan V. Henkelp,s, Michael K. Richardsonp, Stephen P. Mackessyt, Anne M. Bronikowsiu, Mark Yandellj, Wesley C. Warrenl, Stephen M. Secorv, and David D. Pollocka,1
Edited by David B. Wake, University of California, Berkeley, CA, and approved November 4, 2013 (received for review July 31, 2013)
The work reported in the two papers was supported by grant funding from the National Science Foundation and the National Institutes of Health as well as funding from the University of Colorado School of Medicine, UT Arlington and 454 Life Sciences.
Co-authors on the paper from UT Arlington include Daren C. Card, Drew R. Schield, Jacobo Reyes-Velasco, Kyle Shaney, Jill M. Castoe, Eric N. Smith, and Matthew K. Fujita. The title of the paper is "The Burmese python genome reveals the molecular basis for extreme adaptation in snakes."
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