Did Viruses Teach Us Sex?

Sex is a weird thing. At its core, the process involves a cell from one organism meeting up with another cell from another organism. These two cells have to become one when they collide, and they do this by fusing. New evidence suggests that the molecules responsible for this fusion might have come from viruses.

A new paper in the journal Current Biology noticed that proteins called fusogens in a single-celled organism are remarkably similar to another group of proteins produced by several types of viruses. Both types of fusogens are responsible for cell fusion in their respective organism/virus. In the single-celled organism, called Tetrahymena, fusogens dot the outside of the cell and allow the cells to undergo fusion and a primitive version of sex. Viruses, on the other hand, use fusogens to invade their cellular hosts.

mating_tetrahymena
Sex in Tetrahymena — Image: Jmf368w (CC BY-SA 4.0 via Wikimedia Commons)

The researchers involved in the present study were surprised when they saw just how similar Tetrahymena and viral fusogens look. Since proteins are just long strings of amino acids that are folded into complex shapes, we can represent a protein as a string of letters similar to what is done with DNA sequences. Then we can use a computer program to align the protein strings together by similarity. If two protein sequences align with a great deal of similarity–such that there is relatively little difference between the amino acid sequences of the two–it is often inferred that the proteins share a recent ancestor in evolutionary time. This is because evolutionary change is due to change at the DNA level, and the DNA change ultimately determines the protein change. When the viral and Tetrahymena fusogens were aligned, they appeared to be closely related based on similarity.

Not only did viral and Tetrahymena fusogens look strikingly similar, but the researchers were also able to show that they behaved quite similarly in a test tube. Specifically, they were similar in how they interacted with the chemicals that make up the exteriors of cells. The researchers concluded from this that both the structure and function of fusogens are conserved between viruses and Tetrahymena. When we see conservation of structure and function in biology, it is usually suggests that structures share an evolutionary origin.

So could viruses have passed sex on to us by leaving behind fusogens in our ancestor’s cells? Maybe, but the team that wrote this paper is not sure, and even admit that it might have happened the other way around. The bottom line is that we will need more evidence to know for sure, but this is certainly good circumstantial evidence that sexually reproducing organisms might owe a debt of gratitude to our infectious viral frenemies.

Sequencing the World

It looks like the beginnings of a consortium are taking shape, with the goal of sequencing all life on earth. As something of a genomicist, I am psyched by the goal, unattainable as it may be. I also want to say why lofty goals are helpful, and this one will be too.

The Human Genome Project took years to finish, and ended up costing about a dollar per base-pair, which are the chemical “letters” that make up the genetic code. Since then, sequencing has become orders of magnitude cheaper. The current genome sequencing leader, Illumina, famously announced that sequencing a genome could be done for a thousand dollars. If we compare that to the investment required for the human sequence, we certainly have made strides. This is due  to the technology we use to sequence genomes. The most popular way to do it today is to take a sample of DNA from an organism, which is typically present in long stretches of DNA called chromosomes, and break it into short fragments. Since we have a lot of DNA in the sample, we end up having more than one copy of each letter of the genome. Using the powerful genome sequences that we have developed , we can sequence a little bit of each of these fragments before using a computer program to take the short reads and assemble them into a contiguous sequence. If you can imagine taking a few hundred copies of “Moby Dick” and randomly cutting out stretches of letters before trying to reassemble the book from the fragments by looking for overlap between random fragments, then you understand the basic strategy that genome sequencing uses today.

In spite of the cutting edge technology, it still takes a ton of work to go from a draft genome assembly–which is what you could immediately get after putting a thousand dollars into an Illumina machine and plugging the resulting reads into the computer to assemble–to the kind of gold-standard genome assemblies that we have in well-studied organisms like mice and humans. Typically, more work has to be put in to fill in gaps in the assembly that result from highly repetitive DNA, which confounds assemblers. Scientists sometimes have to do follow-up experiments to prove that their genome assembly is real and is not just a computer error. Finally, the genome sequence is useless until you start to figure out where the genes and other features lie. This means more follow-up experiments and comparing the genome to those of other related organisms.

All of this take a significant investment of time and treasure, and there is no way that we could do that for all life on earth. You would never be able to have a gold-standard genome assembly for every organism on earth. Much like the oft-told anecdote about restaurants in New York City–where it is said that you could never eat at every restaurant in the city because new ones are opening for business and going out of business faster than you could visit them all–new organisms are evolving and going extinct all of the time. The idea of putting in enough work to get something as polished as the fruit fly genome, let alone the mouse or human genome, is laughable if you start to think about it. But it would allow researchers to gain an appreciation for the diversity of life that exists on earth, specifically at the DNA level. Just having fractions of the genomes of most of the species on earth would allow us to better understand the evolutionary relationships between all life on earth.

As for this goal being a little too big to handle, big goals are important to push us to new heights. Getting to the moon seemed ridiculous at the time, and sequencing the human genome was impossible when we first started to plan how to do it. These goals ended up being attainable, but just imagine if they had not been. Even if we had never made it to the moon, we would have still developed the kind of technology that allowed us to put satellites into orbit that now power our ubiquitous mobile devices. Even if the human genome proved intractable, we would have still ended up with improved sequencing technology. This is because setting these lofty goals has the effect of pushing us to achieve things that we would have never thought to accomplish without a lofty goal. If we set out sequence all life on earth, just imagine what we might find we can do along the way.

*I found a post by professor/blogger Jeff Ollerton who also had his own take on the proposal. While he and I do not agree, he has an interesting take that I enjoyed reading. It should also be said that he has more expertise than me in this area.

Don’t Stick to Science

I have not experienced it firsthand, but I have heard a lot about “stick to X” phenomenon. Specifically, we all have our area of expertise. Some of us are doctors, some are bricklayers, some are chefs. That is how we pay the rent. Some of us either choose or are compelled to interact with the wider public about this specialty. Writers necessarily put themselves out there and broadcast their expertise to the world. Some scientists with writing habits do that too. Those of us with blogs or enough recognition to get published in periodicals put our views on the progress of science out there for wider consumption.

But we all have ancillary interests too. I am a scientist with a real interest in baseball and politics (real original, I know). If I were a little more well-known, I would probably have eggs in my Twitter mentions telling me to “stick to science” whenever I share a political opinion. In fact, plenty of scientists and other writers I follow have shared stories about people tell them to stick to their respective area of expertise. The whole idea of sticking to X is ridiculous. I have never known a bricklayer or other blue-collar worker shy about sharing their political beliefs, so why should I?

I have been thinking about this a lot more lately because I have been thinking a lot more about politics. As an American–and a progressive one, at that–I have been shocked by the new presidential administration. I feel compelled to share my opinions with my followers. Luckily, it does not seem like I am the only one. Plenty of scientists that I follow have started to speak up. Some are concerned about the way the new administration will employ–or not employ–evidence-based policy-making. Others have broader concerns about the effect Trumpism might have on the culture of diversity and inclusion that we progressives idealize. I believe that it is critical that we not be afraid to share these opinions. Too many scientists that I know have tunnel-vision, unable to see beyond the next grant to be written, the next committee to chair, or the next experiment to run. I swear, I thought some of these folks did not even know that 2016 was a presidential election year until November 7. But we have a lot to share with the world. We scientists are intelligent, rational people, and our expertise should not be pigeonholed. If you think that scientific training only matters in the field of science, then you might as well set up your lab on a deserted island and never leave. You are not doing science any favors by pretending that we are separate from the rest of the world. So I implore those of you who have been silent: start a blog, tweet up a storm, write a letter to the editor. Stay as up on local politics as you do on the latest issues of Nature and Cell (news articles are, by design, much easier to read than papers). Hell, run for office if you have the chance. You can have it all, and in doing so we will make sure that the scientists of the next generation feel comfortable being citizens as well as scientists. Remember, we cannot do science in a vacuum (unless you are a particle physicist, I mean), and the continued success of the scientific endeavor is not preordained. We have to advocate for our science, our way of solving problems, and our vision of the world. The world will be better for it.

Another Zika Structure…and a Mea Culpa

From time to time, I make a mistake by failing to keep up with the primary scientific literature as closely as I should. If I had been on my grind, I would have noticed that another Zika structure was published in Science at around the same time as the Nature structure that I blogged about earlier. The group that put together this structure also compared the Zika particle to related viruses, this time choosing to focus on a region of the viral protein coat that is especially dissimilar to related viruses. The authors go on to suggest that this region of the coat may be involved in attaching to host cells, which could explain how transmissible Zika is compared to its relatives.

Scientists Publish Zika Snapshot

(Image credit: Kostyuchenko et al. (2016) Nature.)

Update (4/27/2016): Science also published a Zika structure, drawing complementary conclusions from it. I thought it would be a good idea to post a small blurb about it here.

A group in Singapore published a structure of the Zika virus particle in Nature on Wednesday. Zika, which the Centers for Disease Control recently concluded is responsible for birth defects in children of infected mothers, has become a growing public health concern.

Victor A. Kostyuchenko and his colleagues at the Duke-National University of Singapore Medical School used cryo-electron microscopy to see the structure of Zika particles incubated at different temperatures. Importantly, the scientists found that the Zika particle is stable over a broader range of temperatures than other related viruses. On a practical level, this could mean that the virus is more transmissible than related viruses, and may be more challenging to control.

Virus particles are simply genetic material–either DNA or RNA–surrounded by a protein coat that protects and transports the genetic material. When the protein coat comes into contact with a susceptible cell, the virus can inject its genetic material into the host. The virus then uses its own genetic material to take over the cell’s own protein-producing machinery in order to produce more viruses. Eventually, those new viruses will be released and go on to infect other cells.

The authors note that their structural model can allow others to find drugs that may destabilize the virus. The hardiness of the Zika particle is almost certainly due to a tough protein coat, but certain drugs may make that protein coat more susceptible to degradation at higher temperatures or other harsh environments. All of this can be used to help stem the transmission of the virus.

For more information, check out the article at Nature: http://www.nature.com/nature/journal/vnfv/ncurrent/full/nature17994.html