December 3, 2013
Extreme Genomic Evolution Discovered In Burmese Pythons
[ Watch the Video: Genomics Reveal The Evolution Of Snakes ]
April Flowers for redOrbit.com - Your Universe Online
A team of researchers have sequenced the genome of the Burmese python, or Python molurus bivittatus, finding large numbers of rapidly evolved genes in snakes.
Their findings, published in Proceedings of the National Academy of Sciences (PNAS), reveal that these genetic changes are linked to extreme characteristics in snakes. The discovery of these characteristics, which include rapid increases in metabolism and organ growth after feeding, open a novel window into how evolution works at the molecular level.
"The bottom line is that snakes have undergone incredible changes at all levels of their biology, from the physiological to the molecular," said David Pollock, PhD, Associate Professor of Biochemistry and Molecular Genetics at the CU School of Medicine. "Snakes appear to have functionally evolved much more than other species. They are a crucible of evolution."
Pollock collaborated with Todd Castoe, a former postdoctoral fellow at the CU School of Medicine now at the University of Texas at Arlington, and an international team of researchers from four countries. They found that snakes carry large numbers of proteins with signatures for positive selection in their ancestors.
"One of the fundamental questions of evolutionary biology is how vertebrates with all the same genes display such vastly different characteristics," Castoe said. "The Burmese python is a great way to study that because it is so extreme. We'd like to know how snakes uses genes we all have to do things no other vertebrate can do."
Positive selection in hundreds of genes is linked to extreme characteristics of the snake such as in metabolism, spine and skull shape and cell cycle regulation.
"When you have positive selection you have a lot of adaptation going on," Pollock said. "Positive selection is rare, but when it happens we are curious. What we are seeing in snakes is unprecedented."
These multiple adaptive bursts caused evolutionary redesign of many proteins in the snake, said the researchers.
"We first saw these unusual molecular patterns in the snake mitochondrial DNA, and now it seems they extend throughout the nuclear genome," Pollock said.
After Burmese pythons eat, the team found that they experience massive changes in gene expression linked to 35 to 100 percent size increase in their heart, small intestine, liver and kidneys in a 24 to 48 hour period. This is an example of physiological remodeling. As the digestion completes, the snake's organs return to their original size within a matter of days. The researchers suggest that gaining a better understanding of how snakes accomplish such enormous feats could hold vital clues for the development of treatments for many human diseases.
Normally the lowest of any vertebrate, the snake's metabolism ramps up significantly. According to Pollock, the increase is akin to a horse going from standing still to running a quarter mile race. The snake isn't moving, however, only digesting.
"Genes that were fully off are now full on," he said. "Snakes eat animals as big as themselves. Once they catch something that size, they need to digest it quickly before it rots in their stomach, and they have to turn a lot of genes on to do it."
"The Burmese python has an amazing physiology. With its genome in hand, we can now explore the many untapped molecular mechanisms it uses to dramatically increase metabolic rate, to shut down acid production, to improve intestinal function, and to rapidly increase the size of its heart, intestine, pancreas, liver, and kidneys," said Stephen Secor, associate professor of biological sciences at the University of Alabama. "The benefits of these discoveries transcends to the treatment of metabolic diseases, ulcers, intestinal malabsorption, Crohn's disease, cardiac hypertrophy and the loss of organ performance."
Phenotypic novelty in snakes appears to be driven by the system-wide coordination of protein adaptation, gene expression and changes in the genome structure, the study notes.
The findings can offer insights into how evolution works at the molecular level, as well as having implications for humans. Snakes contain many of the same genes as other vertebrates, so investigating how these genes have evolved to produce such extreme and novel characteristics may eventually explain how these genes function. Understanding these functions, such as how they enable extreme feats of organ remodeling, could someday be used to treat human diseases.
"What we are seeing now can apply to people," Pollock said. "We can link mutations to physiological effects and perhaps find a way to stop those mutations before they cause disease. There are any number of possibilities and we are only starting to unravel them."
COMPARING THE KING COBRA
Along with a companion paper also published in PNAS detailing the genome of the King Cobra (Ophiophagus hannah), these studies represents the first complete and annotated snake genomes.
The python and king cobra studies represent a significant addition to the field of "comparative systems genomics – the evolutionary analysis of multiple vertebrate genomes to understand how entire systems of interacting genes can evolve from the molecules on up," according to Pollock
He said, "I believe that such studies are going to be fundamental to our ability to understand what the genes in the human genome do, their functional mechanisms, and how and why they came to be structured the way they are."
To accomplish both studies, the team aligned 7,442 genes from the python and cobra with gene sequences available in the Ensembl Genome Browser from other amphibians, reptiles, birds and mammals. They analyzed the data using a statistical method called "branch site codon modeling" to look for genes that had been positively selected (or evolutionarily changed due to natural selection) in the python, the cobra, and early in snake evolution in the common ancestor of these two snakes. The data revealed changes in hundreds of genes.
The research team believes the results demonstrate that natural selection-driven changes in many genes that encode proteins contributed substantially to the unique characteristics of snakes.
The research team found that the extreme characteristics in snakes could also be linked to duplications or losses in multigene families -- in addition to changes to individual genes and their expression -- including ancient loss and more recent re-evolution of high resolution vision, and their ability to detect chemical cues from the environment.
The team noted that, despite the fact that most assume that reptile genes change at a very slow rate, snake genomes are evolving at one of the fastest rates for any vertebrate.