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Today, the Wilke lab has published two studies on the selective pressures that protein structure exerts on evolving genetic sequences. [ The first,] published in BMC Evol. Biol., looks at broad evolutionary trends in yeast. This study shows that evolutionary rate varies linearly with relative solvent accessibility of residues (RSA, a measure for how close to the surface or the core of the protein a residue is located). Hence, more exposed residues evolve faster than more buried residues. [ The second study], published in Mol. Biol. Evol., uses the insight gained from the first to identify individual sites in viral protein that evolve more rapidly or more slowly than expected given their RSA. When applied to two proteins of the influenza virus, hemagglutinin and neuraminidase, this method identified sites involved in cell entry, antibody binding, and drug resistance.
<font size="4">Bringing Molecules Back into Molecular Evolution</font>
<br> <font size== 04/01/2012—Matthew "4">Matthew Tien wins NSF Graduate Research Fellowship ==</font>  Posted on 04/01/2012
Matthew Tien, an undergraduate researcher currently working in the Wilke lab, has been awarded an NSF Graduate Research Fellowship in this year's competition. For his graduate work, Matthew will be joining [ Allan Drummond's laboratory] at the University of Chicago. Matthew plans to use mass spectrometry to investigate the world of mistranslated and misfolded proteins.
<br> <font size== 04/22/2011—Contact "4">Contact networks shape parasite evolutionary trees ==</font>  Posted on 04/22/2011
The inference of population dynamics (such as the number of infected individuals as a function of time) from molecular sequence data is becoming an important new method for the surveillance of infectious diseases. We have examined how heterogeneity in host contacts shapes the genealogies of parasitic agents. We find that contact heterogeneity can have a strong effect on how the structure of genealogies reflects epidemiologically relevant quantities such as the proportion of a population that is infected. Contact heterogeneity also can increase the number of sequence isolates required to estimate these quantities over the course of an epidemic. Our results suggest that data about contact-network structure will be required in addition to sequence data for accurate estimation of a parasitic agent's genealogy. This work is published in a special issue of the journal Perspectives on Infectious Diseases focused on [ network perspectives on infectious disease dynamics].
<br> <font size== 03/04/2010—Universal "4">Universal trend of reduced RNA stability near translation-initiation site ==</font>  Posted on 03/04/2010
In an analysis of 340 complete genomes from bacteria, archaea, and eukaryotes including fungi, plants, insects, fish, birds, and mammals, we have found a universal trend for reduced RNA stability near the translation-initiation site. With few exceptions, the secondary structure of mRNAs is less stable than expected in the first 30-50 nucleotides downstream from the start codon, but is more stable than expected further downstream. The effect is strongly correlated with genomic GC content — the higher GC the stronger the destabilization effect — and, in prokaryotes, with growth temperature — the lower the optimal growth temperature, the stronger the destabilization effect. These observations are consistent with a thermodynamic hypothesis that stable RNA secondary structure near the start codon can interfere with efficient translation initiation. This work is published in the February issue of [ PLoS Computational Biology.]
<br> <font size== 02/24/2010—NSF "4">NSF funds BEACON, a Science and Technology Center in Evolutionary Biology ==</font>  Posted on 02/24/2010
The Wilke lab is part of a $25 million, multi-university center that will study evolution in action in natural and artificial settings. The center is called BEACON, "Bio/computational Evolution in Action CONsortium." It will be headquartered at Michigan State University. Other participating universities are The University of Texas at Austin, the University of Washington, the University of Idaho and North Carolina A&T State University.
<br> <font size== 01/05/2010—New "4">New York Times article on lethal mutagenesis ==</font>  Posted on 01/05/2010
In today's issue of the New York Times, Carl Zimmer discusses the prospects and challenges of [ combating viruses with lethal mutagenesis]. The article features some of the work done in the Wilke lab as well as work done by our colleagues and collaborators in the Bull lab.
<br> <font size== 09/16/2009—Novel "4">Novel source of HIV-1 viremia in patients on HAART ==</font>  Posted on 09/16/2009
Even though highly active antiretroviral therapy (HAART) can reduce HIV-1 virus load to clinically undetectable levels, the virus never completely disappears and ultrasensitive assays can detect small quantities of virus in all patients on HAART. The exact origin of this virus is unknown. Many researchers assume that it is produced by latently infected CD4+ T cells that reactivate. [ We analyzed] HIV-1 sequences isolated from resting CD4+ T cells, activated CD4+ T cells, and blood plasma using a population-genetics approach. Our analysis showed that sequences from resting and activated CD4+ T cells formed a single population, whereas some of the virus in the blood plasma seemed genetically distinct from the virus in CD4+ T cells. This result shows that circulating CD4+ T cells are not the only source of residual viremia, and it suggests that a novel cellular source may contribute significantly to ongoing virus production under HAART. This research was featured by [ Science Daily].
<br> <font size== 06/15/2009—Translational"4">Translational-accuracy selection protects buried and structurally important sites==</font>  Posted on 06/15/2009 
In 1994, Akashi proposed that translationally optimal codons, codons that are translated with relatively low error rate, should preferentially be located at important sites in coding sequences. This signal would be the consequence of translational-accuracy selection, i.e., selection to minimize the amount of non-functional or misfolded protein produced by translation errors. Traditionally, the importance of a site under Akashi's test has been assessed by evolutionary conservation. The July issue of Mol. Biol. Evol. contains a study by [ Zhou et al.] that correlates the location of optimal codons with sites that are important for protein structure. The study finds that there is a tendency of optimal codons to appear at structurally important sites in a wide range of organisms. The study lends further credence to the mistranslation-induced protein-misfolding hypothesis, which argues that much of the selection pressure on coding sequences stems from the toxic effects of mistranslated and misfolded proteins.
<br> <font size== 05/20/2009—HIV "4">HIV viral-load dynamics under Raltegravir==</font>  Posted on 05/20/2009 
The spectrum of anti-HIV drugs was recently extended by a new class of drugs, the integrase inhibitors. The first drug of this class that received FDA approval is Raltegravir. Clinical data show that when previously untreated patients start treatment on Raltegravir, their viral load declines more rapidly than it does in patients who take instead the reverse-transcriptase inhibitor Efavirenz. This spring, Antiviral Therapy published a modeling study by [ Sedaghat et al.] that discusses the possible mechanisms responsible for this accelerated decline in viral load. The study argues that the accelerated decline is likely not caused by greater antiviral efficiency of Raltegravir compared to Efavirenz. Instead, because Raltegravir acts later in the viral life cycle than Efavirenz, at the beginning of Raltegravir therapy fewer cells have progressed to a state where the drug can not inhibit virus production, and hence the viral load declines faster. The study is a follow-up to a paper published in 2008 in [ Proc. Natl. Acad. Sci. USA].

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