Our oceans are getting warmer and more acidic every year, and as a result, coral reefs are rapidly dying.
Biologist Mikhail Matz has been carefully monitoring this decline, awaiting evolutionary developments that may signal better news.
“Corals have a substantial potential to evolve, and I want to see how they do this,” said Matz, assistant professor of integrative biology at The University of Texas at Austin, and an expert on coral DNA. “This is about basic science. Evolution is happening right now. Let’s see how it works.”
Only a few years ago, studying an organism like coral through its DNA would have been impossibly expensive and time-consuming. However, with the emergence of next-generation gene sequencing devices, scientists have been able to move beyond mice, flies and monkeys — the traditional platforms for DNA research — to study a wide variety of organisms based only on their genomes.
In 2009, using the “next-gen” sequencers at The University of Texas at Austin, Matz and his team sequenced the entire transcriptome of the common Pacific coral in less than one year, and at a fraction of the cost of previous efforts. This was one of the first successful full-transcriptome sequences for a non-model organism and generated a flurry of scientific publications and popular press coverage.
The transcriptome is the set of RNA molecules that reflects the genes that are actively expressed at any given time. Unlike the genome, which is fixed, the transcriptome can vary with external environmental conditions, so for Matz purposes, it is a much better resource than genome, providing a concise summary of the essential genomic information relevant to the study of evolution.
“You can mine it for the sequences of adaptation-relevant genes, and for genetic variation by which to trace the evolutionary process in natural coral populations,” explained Matz. “It also represents a knowledge base to profile gene expression in a variety of environmental conditions.”
However, sequencing an organism’s transcriptome is only one part of the discovery effort. The more complicated aspect of DNA analysis involves interpreting the genetic data, performing system-wide analyses, and learning how gene expression leads to diverse physiological outcomes.
Using the Ranger supercomputer at the Texas Advanced Computing Center (TACC), Matz has been exploring the massive amounts of genetic information produced by UT’s sequencers. Through his analysis, Matz helps advance the theory of how genotypes (the genetic constitution of an organism) relate to phenotypes (an organism’s observable traits), and how evolution happens — which would tell us about more than just corals.
“How does the genome drive variation in gene expression, and how is that related to physiology?” Matz asked. “We want to forge those links.”
Unusual worms showcase newest adaptations
In addition to the coral populations, Matz has been working with biologist Svetlana Maslakova at the University of Oregon to study the phylum Nemertea (commonly known as ribbon worms), which, in recent history, developed a radically new larval body-form.
“When we compare these worms with their closest relatives — worms of the same phylum that did not evolve this way — we may be able to answer the question of how this new body plan arose at the genome level,” explained Matz. “Where do the genes come from? How does the system level network get re-organized?”
Matz and Maslakova sequenced the developmental transcriptome of the nemertean worm. Their pool of sequence information allows them to go fishing for developmentally interesting genes, and to quantitatively analyze data on the expression of a large number of genes during development. By studying this data, they hope to identify where in the genetic sequence the instructions for a new larval form emerged, and to pinpoint the changes that made it possible.
“’Next-generation’ sequencing technology allows us to bring genomics tools to studies of non-model organisms, whose genomes have not been sequenced yet, and may not be for a while,” said Maslakova. “This way we can begin to understand how development is regulated at the genetic level, and eventually, how development evolves.”
Methods for interpreting sequences
Beyond studying these biological models of interest, Matz is one of the first to develop the methodology that will allow the broader biological community to use next-generation sequencing effectively.
“We want to develop a standard approach based on next-generation sequencing, so that anybody could do this for any non-model organism,” said Matz.
Currently, next-generation sequencers produce so much data that comprehensive interpretation is nearly impossible. However, Ranger’s massive size and speed let Matz experiment with the data streams delivered by UT’s Applied Biosystems SOLiD sequencer and Roche 454 sequencer — the most advanced products on the market. These experiments help determine what should be sequenced first, which parts of the output are useful and which unnecessary, and which bioinformatics tools should be applied.
Ultimately, the process of interpreting gene sequence data will be accomplished on a powerful desktop computer, not a supercomputer. To reach that goal, Matz needed all the compute resources he could get.
“We wouldn’t be able to do anything without TACC,” said Matz. “We can generate massive amounts of sequences, but then what? The main challenge is to figure out the most appropriate and effective way of dealing with this huge amount of data, and extracting the information you want.”
Matz’s studies are helping genomics and bioinformatics realize the promise of better health, better crops, and a better understanding of evolution and biology generally. He expects a set of guidelines for genetic studies to be in place by early 2011.
“Only now are people realizing what next-generation sequencing can do,” said Matz. “We’re trying to show people how to make use of this wonderful new toy.”
As he develops the gene-sequencing methodology, Matz continues to analyze the coral results, waiting for the telltale signature of evolution, and the emergence of a climate-change-tolerant coral. He anticipates that coral will actually do quite well in the end, thanks to the evolutionary adaptation to the new conditions.
“The corals are dying, yes, but that’s a part of evolving,” said Matz. “It may sound cynical, but this is a golden opportunity to study how evolution happens.”
- Written by Aaron Dubrow, TACC
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