A bonus Wednesday blog post! Today’s BEACON Researchers at Work post is by MSU graduate student Justin Meyer.
For as long as I can remember I have been fascinated by the natural world. Whether it is the chameleon with its capacity to change colors, ants’ collective behavior, or virus’s ability to highjack the machinery of cells, the great variety of organisms alive has inspired my curiosity. As I became more interested in biology I learned that despite the complexity of life forms, there were physical processes such as evolution by natural selection that are responsible for producing them. With this awareness I realized that there was in fact reason behind the seeming chaos of a jungle or an eclectic coral reef. From then on my interests in the natural world extended beyond learning about organisms, but how evolutionary processes such as natural selection shaped them.
Today I study the evolution of a particular group of organisms, viruses, and how they evolve to exploit new hosts. To do this I study how one particular virus, called phage λ (“lambda”), evolves to exploit new genotypes of its host, the bacterium Escherichia coli. I perform my studies by co-culturing the virus and its host in the lab and observing how the virus adapts by genetic mutations to better exploit its host. Since viruses have a short generation time and high mutation rate, I am able to watch the evolutionary process occur over days and weeks rather than the millennia that would be required for long-lived organisms. I find this research particularly rewarding because I am able to watch the hidden evolutionary processes that shape the world’s biodiversity.
One of the most interesting results I have found is when I observed λ evolve to exploit a new receptor on the outer membrane of E. coli. Receptors are proteins or other cellular features viruses use to recognize their host cells as opposed to other cells that they cannot exploit. λ also uses the receptor to bind to the cell and inject its DNA into the host. Once the viral DNA enters the cell, it tricks the host into making more viruses rather than to grow itself. Eventually the cell becomes overrun by viruses, explodes, and releases the new virions. Receptors can be viewed as viruses’ gateway into their hosts and have a major role in determining what species they infect. Therefore evolving to exploit a new receptor is an important event in the evolution of viruses.
I am interested in studying this process for a number of reasons: First, explaining how organisms evolve novel functions daunted even Darwin and remains a relatively unexplained phenomenon today. I hope that my research will fill this unexplored part of evolutionary biology. Secondly, these transitions mark important events in the evolution of disease and by studying them we may be able to design techniques to predict, monitor, or stifle the emergence of future diseases. Lastly, learning the ecological and evolutionary pressures that drive the evolution of novel functions could have bioengineering applications, such as engineering viruses to deliver genetic medicine or bacteria to remediate pollution.
The process by which λ evolved the new function was pretty fascinating. First, the event that triggered λ’s evolution was not an evolutionary change in λ itself, but was a change in its host. E. coli evolved resistance to λ infection by turning off production of the receptor protein, named LamB. This was accomplished through mutations in a gene, malT, that up-regulates LamB. By knocking out the receptor, the E. coli gains complete immunity to the virus. Fortunately for λ, the mutation is not perfect and occasionally an unlucky cell expresses LamB and becomes infected by λ. The virus is therefore able to reproduce and maintain a modest population, however it experiences pressure to improve on the resistant E. coli and regain its abundance. At this stage the virus acquires mutations that improve its binding to the very rare LamB molecules. These mutations are thought to make the virus less picky so that if it encounters a LamB molecule, it does not miss the opportunity to attach to it and infect a cell. Eventually a combination of four mutations evolves that together confer the ability of λ to exploit a new outer-membrane protein, OmpF, in addition to LamB. Interestingly, this sequence only happens in a quarter of the experimental trials. For the other three quarters of the time λ remains reliant on LamB because the host cells evolve a second round of resistant mutations that block the virus from infecting even if it acquires the ability to target OmpF.
There are two notable findings from this work. The first is that mutations evolved to improve an ancestral function can be co-opted for a new function. This observation shows that evolving new functions may be easier than often assumed if old parts can be put together to create new innovations. Secondly, whether λ evolves this key innovation is not dependent on the evolutionary path it takes, but instead is dependent on the host. One set of mutations in the host promotes the viral evolution while another set stifles it. This adds an interesting twist to Stephen J. Gould’s thought experiment on the contingent nature of the tape of life and suggests that there are ways to intervene in the process of viral host-jumps.
For more information on Justin’s work, contact him at meyerju3 at msu dot edu.