Thursday, December 12, 2013

The Serpents' Sequence

Scientists recently mapped the full genomes of snakes for the first time!

Actually, 2013 has been a big year for whole-genome sequencing in reptiles.

But let’s back up a step: What is whole-genome sequencing?

A genome is the entirety of an organism’s genetic material – all of its DNA.  Genes – small sections of DNA – code for proteins.  One gene might tell your body how to make a certain type of protein, and that protein might help build cells, or catalyze chemical reactions, or do pretty much anything else your body needs.  If you think of genes as the body’s instructions, then the genome is the entire blueprint.

Back in the early 1990’s, a group of scientists from various institutions in several countries embarked upon a legendary task: to describe and record the entire human genome – every gene in the body.  The Human Genome Project took over ten years to complete, but finally in 2003, these scientists published the full human whole-genome sequence for the first time - a full list of about 20,500 genes.  The Human Genome Project was one of the most monumental achievements of recent science, and it has led to incredible advancements in our understanding of human development, evolution, and especially genetic diseases.

The techniques developed during the Human Genome Project have allowed scientists to dive into the genomes of other organisms as well.  It is one of the beautiful side-effects of evolution that there are genetic similarities between all living organisms, particularly those that are closely related to each other.  So studying the genomes of other organisms can teach us a lot, not only about those creatures, but about ourselves as well, and about a wide range of topics including genetics, evolution, physiology, and medicine, to name a few.  To date, full-genome sequences have been achieved for a long list of organisms, from bacteria to fungi to fish to mammals.  Wikipedia has some great extensive lists (These lists might not be entirely up-to-date though!  As of my writing this, one of the animals I mention below is missing from Wikipedia’s list).

The Burmese python (left) is one of the largest reptiles in North America,
and a problematic invasive species. The King Cobra (right) is the longest
venomous snake in the world.
Which brings me back to the main point: Scientists recently mapped the full genomes of snakes for the first time!  Within the last month, scientists have published the whole-genome sequences of the Burmese python (Python molurus bivittatus) and the King Cobra (Ophiophagus hannah), the first two snakes to get the full-genome treatment.  These studies have unlocked a host of neat information about snakes.  What kind of information, you ask?  Well, let me list some of my favorite highlights:

  -Dynamic Digestion.  Lots of people have seen videos of snakes eating prey whole, and boy is it awesome.  But what fewer people realize is what happens afterward.  Most of the time, many of the snake’s internal organs are in sort of a dormant state, but after it eats, its internal systems change rapidly: organs expand in size; metabolic activity skyrockets; the heart works overtime; systems come alive to process the snake's meal.  It’s a massive physiological makeover, and it happens within days.  Here, watch David Attenborough explain it in this video.
                In studying the python genome, Castoe et al. (2013) investigated the genetics behind this phenomenon.  They found that after the snake eats, its genetic processes shift dramatically; thousands of genes change expression, which is to say they start performing different functions.  You might think of it as thousands of genetic processes ‘turning on’ to help digest the snake's food.  And then, when digestion is complete, these genes switch back to their normal processes again.  What’s more, the genes involved in this magnificent makeover are related to genes involved in metabolic processes, growth and development, and even genes involved in human disease.  Understanding how the snake’s genes perform this way might give us some useful insights into our own health as well.

  -Whence Venom. Of all the attributes of snakes, probably the most commonly studied feature is their venom.  Understanding snake venom not only gives us knowledge about disease and dangers to our own bodies, but also allows us to combat the effects of venom in people who have been bitten.  Snake venom genetics have been studied extensively in the past, but with the full genome of the King Cobra, the longest venomous snake in the world, Vonk et al. (2013) were able to investigate the origins of this snake’s deadly toxins.
                 The most common gene they found coding for the toxins in the cobra’s venom was the gene miR-375, a gene that is commonly found in the pancreas of other vertebrate animals, including some snakes.  This is really interesting, because it implies that these genes, which originally coded for digestive proteins in the pancreas, were evolutionarily hijacked and repurposed to become part of the snake venom, where they help break down the body of the snake’s target.  But these genes didn't just come from the pancreas; the researchers found that many of the genes coding for venom toxins are closely related to genes from a wide variety of other parts of the body.  It seems that the genes underlying the snake’s deadly venom cocktail were collected over evolutionary time from tissues and processes all over the body.

  -Losing Limbs. The researchers also took a look at the snakes’ Hox genes.  These are genes in animals that lay out the body plan during embryonic development.  Basically, these are the genes that determine that the head goes here, the legs go here, the tail goes here, etc.  Any problems with these genes and the body, head, and limbs might not form properly.  In the snakes, the researchers found mostly all of the same Hox genes that humans, lizards, and other animals have, including the genes coding for limb development!
                Now, this is cool, but not really surprising; given that snakes evolved from limbed ancestors, we would expect them to have retained genes coding for limbs (the same way chickens retain genes coding for teeth).  What’s interesting is that one gene in particular – Hoxd12, found in humans, lizards, etc. – is largely absent in the snakes.  Scientists have known previously that Hoxd12 is important for limb growth, but is the atrophy of this one gene the reason for snakes’ limblessness?  Or is there more at play here?  Time and science will tell!

This diagram from Zakany and Duboule (2007) shows what happened in mice embryos
when certain Hox genes were removed.  Clearly very important genes!
  -On the Origin of Snakes.  Okay one more.  One of the biggest questions regarding snakes is “What was their common ancestor, and why did they lose their legs?”  The two big conflicting ideas here are that 1) the ancestors of snakes were swimmers (aquatic origin) or 2) the ancestors were burrowers (fossorial origin).  Both are conditions that may have encouraged limb reduction, as they have in some animals today.  Both sides have evidence, and both sides have proponents.
                Interestingly, these snakes studies took a look at the genes related to vision in snakes, and they found that snakes have about half as many vision-related genes as lizards and other animals do.  This is fascinating.  Loss of vision is a very common feature of burrowing animals, and reduction in vision genes might be something snakes inherited from a burrowing ancestor.  Nail in the coffin?  Debate over?  Nah, it’s not that simple.  But compelling evidence for a burrowing ancestry?  Absolutely!

What makes these studies even more exciting is this: not only are these the first two snake genomes published, but they are only the sixth and seventh reptile genomes ever sequenced.  Which brings me to my other main point: 2013 has been a big year for whole-genome sequencing in reptiles.

The first reptile genome sequenced was the green anole in 2011.  So far, the year 2013 has seen the publications of the genomes of three turtles (the Painted turtle, the ChineseSoftshell, and the green sea turtle) and in August, the Chinese alligator.  The genomic studies of the turtles revealed clues about how turtles have developed their unique body plan, and the study of the alligator taught researchers a lot about the genetic basis for the alligator’s exceptional diving ability and extraordinary senses.

Any time I see a new fully-sequenced genome in the news, I get excited.  So much information comes out of these studies that they are always fascinating.  And every new genome we sequence gives us yet another organism to use for comparison to genomes we will sequence later.  Even now, researchers are working on sequencing more reptilian DNA, to be completed in the near future.  2013 was apparently a really exciting year (if you like reptiles!), and I’ll be excited to see what next year brings.

Ooh! Ooh!  I didn’t get to tell you about the coelacanth genome they sequenced in April!  Oh well, maybe next time.

Castoe et al. 2013. The Burmese python genome reveals the molecular basis for extreme adaptation in snakes. (PDF)
Vonk et al. 2013. The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system. (PDF)
Zakany and Duboule 2007. The role of Hox genes during vertebrate limb development. (PDF)

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