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Saturday, August 17

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Genome of the dragon

The story behind the science

Longtime Zoo friends will remember Slasher, our huge and wonderfully tempered Komodo dragon (Varanus komodoensis). Slasher came to Zoo Atlanta in 1993 from the National Zoo and passed away at the age of 20 in 2013. Millions of visitors got to know Slasher, and a great many met him up-close-and-personal, as he hosted one of the Zoo’s very first Wild Encounter programs.  Wild Encounters guests had mouse treats, and Slasher loved mouse treats! Slasher also represented the legacy of Komodo dragons in the United States, because his parents were the original dragons given as a Gift of State to President Ronald Reagan in 1986 by Indonesian President Suharto. Appropriately, the original pair went the National Zoo. As Slasher was aging gracefully, the feisty young Rinca arrived at Zoo Atlanta. Rinca is now a big boy.

Having established the awesomeness of Slasher and Rinca, I’m really here to talk about their genomic legacies.  In 2011, I was contacted by a geneticist from the Gladstone Institute, a research arm of the medical school of the University of California San Francisco. Incongruously, he was interested in a blood sample from a Komodo dragon. Dr. Benoit Bruneau, as I soon learned, studied the genetic basis for heart development. With human hearts, and specifically regarding congenital heart malformations, as his focus he also studied genetics and development of the hearts of other vertebrates. In this sense, his approach is conceptually similar to the Zoo’s own Great Ape Heart Project.

Over the course of our communications, I realized that he had made the connection between the high-metabolism, very mammal-like, metabolism of monitor lizards (the family that includes the Komodo dragon) and the anatomy of their heart, which bears a few features more similar to mammals than to those of other lizards. Dr. Bruneau wanted to try to find and characterize the genes that inform the development of the heart, cardiovascular system and metabolism of a monitor lizard, in order to gain a perspective on normal and malformed human hearts. Specifically, his team was interested in examining the Komodo dragon as their model organism.

Why did they choose the Komodo dragon, from among all the 50-odd species of monitor lizard?  Because they are cool.  Yes, that is the thoroughly scientific answer to the question.  This is why you read our Research Notes, to get the stories behind the science at the Zoo! After discussions with Dr. Bruneau and reviewing his formal research proposal submitted to the Zoo, we decided that this was an interesting and valuable study. What was required of Slasher was a sub-sample of his blood that would be drawn at his next scheduled veterinary exam. Nothing more than that was required.

In 2011, during Slasher’s exam, Dr. Sam Rivera and his Vet Team collected the sample while Slasher blissfully ate mouse treats. I placed it in a special preservative and overnight-shipped it to San Francisco in 2011.  The next phase of the project, in the Bruneau Lab, was going take years. Meanwhile, Slasher was free to attend to his fan base. The blood sample was to be the source of the raw DNA that Bruneau’s team would analyze. In order to find and screen the genes they needed, they made the decision to discover the DNA-code sequence of the entire genome of Slasher.

Recovering the sequence of an entire genome is a massive undertaking, and even more so if the goal also is to identify and locate specific genes scattered along the sequence—known as annotating the genome. This is the reason that only a handful of species have had their entire genome mapped. Genomes are very long sequences and very difficult to understand. Specific genes for certain traits are not arranged in any logical order along the sequence. Some genes have become duplicated many times, so there are multiple copies of the same code present. Some sections of the DNA sequence do not appear to contain any information. Some sections may contain information, but they are not active or available to the animal. This is why it takes years of analyzing the genetic code to determine where the information is located, and what it actually does. Comparing the components of the genomes of these model species, including the human genome (https://web.ornl.gov/sci/techresources/Human_Genome/index.shtml), is how we understand the genetic basis for all the things similar and different between species or individuals.  These genome libraries are research legacies that will inform huge diversity of studies for eternity. So, we were very excited that Atlanta’s favorite lizard was to become a scientific legacy. 

In August 2013, after a few years of expectable silence, Dr. Bruneau contacted me to ask if might be possible to get another sub-sample of Slasher’s blood during his next scheduled physical exam. The team had simply used the entire original sample. Let me remind you that this work is not easy! The timing could not have been sadder, because Slasher had passed away only about a week earlier.  Slasher’s necropsy exam was conducted at the vet school at the University of Georgia, and I realized that there was at least some chance they might have some tissue samples in the freezer still. I called immediately and learned that Slasher’s liver had been stored!  I drove to Athens, collected and preserved a sample from Slasher’s liver, and express-shipped it from Athens to the Bruneau Lab.  But the results were disappointing. The DNA in the liver sample had degraded a bit and was not useable for the project entire. Enter Rinca, Slasher’s stunt double!  We decided to get a sample from Rinca on his next physical exam and splice that into the sequence with Slasher’s DNA to get the full genome. 

Between 2011 and 2019, Bruneau’s international team worked on the project. I would send them updates on Slasher and Rinca. The lab was decorated with their portraits, taken by the Zoo’s Adam Thompson. On several occasions when members of the lab happened to be traveling through Atlanta, they would come to the Zoo and I would introduce them to the reptile stars. Everyone in Atlanta, and San Francisco, and across a growing number of collaborating labs around the world, was so excited to be part of this legacy project. In 2018, the lab work was done, and preparation of the publication commenced. A team of more than 30 specialists from a variety of fields collaborated to write the piece that would introduce the entire genomic sequence of the Komodo dragon and illustrate a few specific features that we discovered among the genes. As the herpetologist on the team, my job was primarily to make sure that the genetics folks framed their findings in ways both accurate and appropriate for the different scales in the contexts of reptiles, lizards, monitor lizards and Komodo dragons specifically. In other words, to make sure that we were making appropriate and logical comparisons among species and interpreting the results in relevant contexts. It was a lot of fun, I must admit.

Now that our paper has been published (see link below), the whole genome of the Komodo dragon is freely available to researchers around the world to use as a comparative resource for their studies on other species, and as the go-to source for identifying the genes that underlie features of monitor lizards and Komodo dragons, specifically. Our team investigated a few genes of key interest to the Bruneau Lab, hitting just the tip of the iceberg in terms of the massive amount of information we just uncovered, organized and presented to the world. For example, the team discovered:

  • A total of 151 genes, many duplicated, related to a particular class of chemosensory receptors. These play roles in the very sensitive sense of smell in these lizards. By comparison, we learned, iguanas do not have so many of these genes. Now we understand the genetic basis for the very different lifestyle of monitor lizards and iguanas.
  • Genes that allow the cells to operate at particularly high metabolic levels. These play a role in enabling the remarkable strength and stamina of these lizards that can walk, run, swim, or wrestle far longer than can other lizards.
  • Evidence of natural selection for genes that increase capabilities of the cardiovascular system, especially with regards to controlling blood pressure during such prolonged bouts of exercise.
  • Specialized genes that regulate blood coagulation. The saliva of monitor lizards in general has strong anti-coagulant properties that appear to be associated with their abilities to overcome prey animals by encouraging copious bleeding after bites. But the animals also bite each other during wrestling fights related to territories and mates. We speculate that these powerful coagulant genes enable Komodo dragons to resist the anticoagulant effects of bites received during aggressive bouts.

Neat stuff here, no doubt. We learned a bit about the genes that enable some of the remarkable capabilities in smell and physical stamina of Komodo dragons, Bruneau’s Lab learned more about the cardiovascular genetics of an unusual lizard that he can use to help interpret the genetics of the human hearts that they mostly study. Most broadly, we contributed an enormous amount of information about a species of lizard that will form the basis for innumerable future studies looking at Komodo dragons, reptiles, vertebrates, or animals in general. I am excited about what we learned and pleased with our team’s contribution to science. But, mostly, I am personally happy to know that Slasher and Rinca are now scientific rock stars with permanent legacies in place, and I am very proud that Zoo Atlanta was the zoo that recognized the potential importance and value of Bruneau’s initial request. We were the zoo that stepped up and contributed to our knowledge of animals in a significant manner.

I’ll be looking forward to seeing you at the Zoo this summer, as Rinca’s hordes of new fans rush to meet the star!

Read the paper here: https://www.nature.com/articles/s41559-019-0945-8.

Full paper citation:
Lind, A. L.,Y. Y. Y. Lai, Y. Mostovoy, A. K. Holloway, A. Iannucci, A. C. Y. Mak, M. Fondi, V. Orlandini, W. L. Eckalbar, M. Milan, M. Rovatsos, I. G. Kichigin, A. I. Makunin, V. A. Trifonov, E. Schijlen, L. Kratochvil, R. Fani, T. S. Jesso, T. Patarnello, J. W. Hicks, O. A. Ryder, J. R. Mendelson III, C. Ciofi, P. Y. Kwok, K. S. Pollard and B. G. Bruneau. 2019. A high-resolution, chromosome-assigned Komodo dragon genome reveals adaptations in the cardiovascular, muscular, and chemosensory systems of monitor lizards. Nature Ecology and Evolution https://doi/org/10.1038/s41559-019-0945-8

Joe Mendelson, PhD
Director of Research

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