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September 09, 2013 | By:  Sedeer el-Showk
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Tracking the Evolution of a Virus

Most of the articles on this blog have talked about evolution as though it were somehow distant, something that happens to unfamiliar organisms and doesn't really affect our daily lives. Nothing could be further from the truth. Evolution didn't just shape the world around us; it continues to mold that world, casting and recasting it as creatures thrive and perish in turn. Some of these stories may seem strange and foreign, but others strike closer to home. In that spirit, I'm planning to write a few posts about evolutionary stories that might affect our day-to-day lives. The first centers around research by an international team of scientists trying to understand where the H7N9 influenza virus came from.

First detected in China in March, H7N9 is the latest in a slew of influenza viruses to have cropped up in the media. H7N9, H5N1, H1N1 — what do all these names and numbers mean, anyway? The 'H' and 'N' refer to two proteins on the surface membrane of the influenza virus, hemagglutinin and neuraminidase, and the numbers indicate the type of each protein. H7N9 has a type 7 H protein and a type 9 N protein.

Schematic depictions of influenza hemagglutinin (left) and neuraminidase (right).
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Both proteins play an important role in the virus' life cycle, which is one reason they're useful for classification. While N proteins help mature viruses break out of a cell so they can spread, H proteins help the virus get into a cell and infect it. They attach the virus to a cell by sticking to molecules on its membrane; the cell then engulfs the virus, pulling it in and pinching off a pocket of membrane to trap the virus in an endosome. When the cell releases acids into the endosome in an attempt to digest the virus, the H protein springs into action again. The acid makes the H protein change shape, grabbing the inside of the endosome membrane and pulling the virus against it. The viral membrane then merges with the endosome membrane, spilling the insides of the virus out to wreak havoc in the cell. Since the H and N proteins get the virus in and out of cells, knowing which type a virus has tells us something about which kinds of cells it can infect. For example, H1, H2, and H3 proteins are found in human influenza viruses, but we can also be infected by viruses with H5, H7, or H9 proteins.

(For completeness' sake, I should mention influenza viruses are first classified as type A, B, or C, and only then categorized by protein type. These three are all type A, so the full name would be A/H7N9. Other subcategories include the year and place the virus was isolated.)

The H and N proteins, along with all the other proteins in a virus, are encoded in its genome. By comparing the genomes of related organisms, scientists can reconstruct their evolutionary history. It's a bit like comparing different versions of a text. One of Shakespeare's most famous sonnets opens with the line "Shall I compare thee to a summer's day?". If we found some copies of the poem that say "summer day" instead, we might speculate that they're from the same source, where the original mistake (summer's → summer) was made. We might even find other copies where the line reads "Can I compare thee to a summer day?". Again, these are probably copies of a single document where "shall" was replaced with "can", but because they also have the summer's/summer change, it's likely that the shall/can switch happened in a version which already had this mistake. In other words, the "can" versions are descendants of the "summer" version. Of course, it's possible that these mistakes happened independently instead of coming from the same copying error, but we can try to estimate how likely that would be and account for it. The technical details are very different when you try the same thing with genes, genomes, and proteins, but the basic idea is the same.

The researchers collected samples from the throats and guts of various birds in three provinces in China and isolated viruses from them. They sequenced the H7N9, H7N7, and H9N2 viruses they found and compared their genomes with those of older strains collected between 2000 and 2013. According to their findings, domestic ducks probably served as a melting pot for influenza viruses from wild migratory birds, allowing various H and N subtypes to mix together in different combinations. From there, the viruses spread to chickens, where they could recombine further, swapping bits with the H9N2 virus common in chickens. The infections eventually spread to live poultry farms, and, at some point, the H7N9 virus gained the ability to infect humans from chickens. It never became able to jump directly between humans, which is fortunate since 44 of the ~135 people who got infected died. Understanding where this virus came from and how it changed along the way can help us know where to look for other threats and prepare for them.

Evolution isn't just a dusty old theory to explain the similarity and diversity of life on Earth. It's more than just a conceptual framework underpinning the rest of biology. Evolution is always happening, a never-ending process of change and discovery and loss, even as you read these words. Not just "out there" somewhere in the wild, but in our cities and markets and schools, in our yards and parks, and even in our own bodies, home to countless micro-organisms. Viruses and bacteria evolve to infect us and continue evolving while they're inside us, learning to cope with our bodies' defenses and our cornucopia of drugs. Ceaseless and unyielding, evolution shapes and reshapes the fabric of this world, an ever-changing tapestry in which our thread is woven.

Some things to ponder:
- Can you think of other ways that evolution is important in our lives?
- Some people to think humans have stopped evolving. What do you think?

Reference
Lam T et al. (2013) The genesis and source of the H7N9 influenza viruses causing human infections in China. Nature Advance online publication. DOI: 10.1038/nature12515
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