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Genome Studies Explore Nature of Burmese Python, King Cobra Adaptations

NEW YORK (GenomeWeb News) – In a pair of studies online this week in the Proceedings of the National Academy of Sciences, independent research teams presented findings from genome sequencing studies of the Burmese python and king cobra — efforts highlighting the rapid genome changes that have occurred in the snake lineage.

"The bottom line is that snakes have undergone incredible changes at all levels of their biology, from the physiological to the molecular," University of Colorado biochemistry and molecular genetics researcher David Pollock, senior author on the Burmese python study, said in a statement.

For their study, Pollock and his colleagues from centers around the world used a combination of Illumina and Roche 454 approaches to sequence the Burmese python, Python molurus bivittatus, genome. They also assessed transcript sequences from various snake tissues at several time points before and after feeding in the python.

By scrutinizing such sequences and comparing genome patterns in the Burmese python with those from other animals, that team determined that a combination of protein sequence, genome structure, and gene expression shifts have likely contributed to specific Burmese python adaptations — from metabolic feats found in the reptile to its ability to adjust its organs while swallowing prey whole.

"We'd like to know how snakes use genes we all have to do things no other vertebrate can do," first author Todd Castoe, who was a post-doctoral researcher in Pollock's University of Colorado lab when the study was performed, said in a statement.

"The Burmese python is a great way to study that because it is so extreme," Castoe noted.

Beyond physical adaptations found in all snake species, he and his colleagues noted that the Burmese python has acquired other unusual attributes, including the capacity to consume and digest large prey.

Past studies suggest that a metabolic boost — together with enhanced intestinal function and a temporary jump in the size of certain snake organs such as the heart, liver, and kidneys — contribute to that process, though the genetic factors making such changes possible were yet to be determined.

In an effort to better understand these and other Burmese python traits, the researchers used Illumina GAIIx, Illumina HiSeq 2000, and Roche 454 GS FLX instruments to sequence genomic DNA from a female Burmese python, generating sequences that covered the snake's genome to a depth of 49-fold, on average.

After putting these sequences together de novo into an assembly spanning 1.44 billion bases of the Burmese python genome, the team did comparative analyses that also included sequences from the king cobra and from other previously sequenced reptiles, amphibians, birds, and mammals.

Along with expansions to certain gene families and streamlining in others, the team saw signs of rapid changes to mitochondrial sequences and signs of positive selection affecting metabolic genes in the Burmese python.

Compared with genomes from related animals, the genome sequence from the stretchy snake also showed a shift in repetitive DNA repertoires, nucleotide substitution rates, and more, authors of the study noted, underscoring the extent of the genome evolution present in the snake lineage.

With the help of transcript sequences from representing tissues in the Burmese python's heart, kidney, small intestine, and liver tissues during various stages of feeding, meanwhile, investigators identified expression changes coinciding with the prey consumption.

Among genes showing the most pronounced expression shifts after a Burmese python meal were members of pathways involved in heart, lung, eye, and kidney function, and genes contributing to skeletal features, development, and metabolic processes.

"Snakes eat animals as big as themselves," Pollock said in a statement. "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."

In another PNAS study, investigators from Leiden University and elsewhere described the genomic, transcriptomic, and proteomic profiling approaches they used to explore the basis of venom production and other adaptations in the Indonesian king cobra, Ophiophagus hannah.

That team used Illumina's GAIIx to tackle the venomous snake's genome, estimated at between 1.36 billion and 1.59 billion bases, generating sequences from an adult male king cobra that were then assembled into a draft genome.

In addition to that genome assembly, the researchers sequenced transcripts and small RNAs from the snake's venom gland, its accessory gland, and a pooled tissue sample. To that, they folded in proteomic profiles from the venom itself.

Together, those data sources pointed to a king cobra venom system that has resulted from tinkering with existing toxin-coding genes and genome systems, researchers reported.

"In contrast to the platypus, the only other venomous vertebrate with a sequenced genome, we find that snake toxin genes evolve through several distinct co-option mechanisms and exhibit surprisingly variable levels of gene duplication and directional selection that correlate with their functional importance in prey capture," Leiden University biologist Michael Richardson, the study's corresponding author, and his colleagues wrote.

The expression of such toxins is distinct in the snake's main venom gland compared to its accessory venom gland, they noted, with the latter organ apparently using certain toxin-like genes to produce non-toxic proteins with yet unknown functions.

And based on microRNAs present in specific snake tissues, the team speculated that small RNAs involved in proper pancreas function in other animals likely regulate the secretory system behind the king cobra's bite.

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