Two Snake Genomes Equals a Good Reading Day

It’s a good week for snake genomics, because PNAS has published both the Burmese python genome (Castoe et al. 2013) and the king cobra genome (Vonk et al. 2013). The related papers come from separate research teams (the python people mostly from Colorado and the cobra cabal the Netherlands), albeit with significant overlap between them. The world of snake molecular biology is a small one, after all.

The python group planted its snake genome flag in the ground more than two years ago with a paper describing their first draft assembly, and I have been eagerly awaiting the  results of their full-blown analysis. It was well worth the wait. As the python is known for its feast-or-famine metabolism (the small intestine can grow up to three times in size after gulping a meal half the python’s body mass), the researchers provided a very elegant analysis of the differential expression of genes in digestive organs before and after a meal and show, basically, that different genes are turned on or off either pre- or post-feeding. Very cool.

Figure 3B from Castoe et al. (2013), showing genes that have undergone positive selection on the vertebrate lineage leading to snakes.

Figure 3B from Castoe et al. (2013), showing genes that have undergone positive selection on the vertebrate lineage leading to snakes.

The authors of the python paper also investigated how snakes evolved their iconic and constrained morphology – because, after all, snakes lack legs and are equipped with a feeding apparatus equivalent to a human being swallowing a 16lb Thanksgiving turkey whole, and the molecular bases of these adaptations are unresolved. They analyzed a large number of genes shared across vertebrates – called orthologs – and found that during the evolution of the vertebrate lineage leading to snakes, many genes associated with skull and spinal development, metabolism and other functions experienced a faster rate of evolution than in other lineages. Also very cool.

Next up: king cobra. Why do we need both a python AND a cobra genome? The answer lies in the difference between these two snakes. One of them – and I hope you guessed cobra – is venomous. So it is no surprise that much of the justification for sequencing the king cobra genome included a need to understand the evolutionary origins and maintenance of the genes that control venom production. The cobra genome contains a multitude of protein families that underwent a significant expansion during cobra evolution that resulted in what we see today – a highly potent mixture of toxins designed to ensure certain death to a chosen prey item.

The two genomes differ vastly in their qualities of assembly. Through a mixture of various sequencing methods, the python team was able to get an N50 value of 207kb, meaning 50% of the assembled chunks of contiguous sequence were at least 207,000 base pairs of DNA in length. That assures that the research team would be able to recover the majority of genes – exons and introns and all. The cobra genome by contrast has an N50 value of only 3,982 base pairs, meaning that some of the genes may be fragmentary and the length of many introns will remain unresolved. However, I think that using N50 as a the gold standard of genome assembly “quality” is misleading. Sequencing strategies that significantly raise N50 values cost more money. In this day and age of modern biology, where small labs or groups of researchers conjure up whatever resources they can for an in-house genome sequencing project, the most affordable strategy for however you wish to address your biological questions will probably suffice. Both of these snake genome papers make the cut in that regard, and they are a significant contribution to the field of reptilian genomics.

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The Age of Reptiles

On the eve of the publication of the Anolis genome paper in the journal Nature, it is an exciting time to study reptile evolution. Before 2005, there were no reptile genomes available. Anolis was chosen to be the first genomic representative of an extremely diverse class of vertebrates, an account of this process is provided by Harvard University professor Jonathan Losos on his Anolis-themed blog Anole Annals.

Even though the paper will be published in 2011, the Anolis genome has been available since 2007 (it must be exceedingly difficult to write a paper with a few score plus authors), and a variety of researchers pounced on the chance to study the first reptile sequence. For instance, it has been observed that the Anolis genome lacks isochores which are common in other vertebrates (Fujita et al. 2011). We published a paper reviewing the impact of transposable elements (TEs) in the Anolis genome (Tollis and Boissinot 2011), which I synopsized in a recent post on Anole Annals.

In our paper, we discuss Castoe et al. 2011 which describes TEs found in two snake genomes, Burmese python and copperhead. There is currently a python genome project as well, and the first draft of this genome is already available. The python belongs to an ancient group of snakes and is well studied due to its ability to withstand extreme metabolic shifts as a result of the serpentine feast and famine lifestyle.

The Ed Green lab and the Genome Technology Center at UC Santa Cruz is working on the alligator genome. Alligators and crocodiles are the closest living relatives of birds, and together they form a group called archosaurs. This was a successful and diverse group during the Mesozoic Era, and extinct members include all non-avian dinosaurs and pterosaurs. The alligator genome will teach us more about this important branch of the vertebrate family tree. In addition, an alligator genome will have value to human health because of their incredibly complex and robust immune systems (they live in rank swamps and rarely get infections). More crocodilians are being sequenced as well, and their genome dynamics are an active area of research (see David Ray’s lab page at Mississippi State).

Python versus Alligator! Python already has his genome sequence available on NCBI so he wins the current battle... but who will win the war? (photo from Wikipedia)

There are several more reptiles that are either being sequenced currently or are being considered for sequencing. The painted turtle will be the first large genome (3Gb) to be sequenced fully with next-generation 454 technology. There is a proposal in place to sequence the garter snake genome as well. It won’t be long before we find ourselves in a new, genomic Age of Reptiles.