The Evolution & Medicine Review

Epistasis in Adaptive versus Stochastic Evolution of the Influenza A Virus Nucleoprotein Gene

Epistasis refers to the influence of one genomic mutation or variant on the phenotypic effects of another mutation or variant.  Based on available evidence and theory, this phenomenon has a major influence on evolutionary trajectories for organisms of all sorts.  The role of epistasis has been studied primarily in the context of adaptive evolutionary change.  In a recent paper (2014), Gong and Bloom attempt to determine the relative frequencies of epistatic interactions in adaptive versus stochastic evolution, i.e. evolution driven by selection as opposed to evolution resulting from random processes without a significant selective ‘pressure.’  Gong and Bloom perform this comparison by analyzing homologous nucleoprotein (NP) genes in human and swine influenza A viruses.  The authors argue that the human viruses are subject to substantially more intense selection than the swine viruses since domestic swine are much shorter lived and their viruses are not as likely to be subjected to immune memory responses. (more…)

Augmented Infection Control via Practical Pathogen Phylogenetics Based on Whole-Genome Sequencing

A major problem confronting physicians, nurses, and other hospital personnel is transmission of pathogens among inpatients or between medical personnel and inpatients (in either direction).  A crucial component in efforts to control such infectious outbreaks in hospital wards is determining whether particular cases are linked by instances of person-to-person transmission.  Standard methods of analysis involve epidemiological data, determinations of antibiotic sensitivities, and evaluation (multilocus sequence typing or MLST) of alleles at a limited number (<1%) of bacterial loci.  A recent paper by Harris et al. in Lancet Infect Dis. (2012) offers results that support the use of whole-genome sequencing (WGS), which covers >95% of loci, of infectious isolates from individuals that might reasonably be thought to be part of an outbreak.  In this particular study, focused on infection by methicillin-resistant Staphylococcus aureus (MRSA), both inpatients and outpatients were likely involved.


Genomic Analysis of a Bacterial Evolutionary Pathway Underlying a Phenotypic Innovation

Peter and Rosemary Grant have been responsible for what must be among the longest-running continuous field studies in evolutionary biology (2011).  It will reach forty years in 2013.  In this work, the Grants closely follow multiple species of finches on the Galápagos Island of Daphne Major.  Their results have provided numerous valuable insights into the nature of evolutionary change. 

The closest comparable study in the laboratory setting, with respect to both duration and the number of insights pertaining to the nature of selection and evolution, is perhaps the Long-Term Evolutionary Experiment (LTEE) of Richard Lenski and his associates at Michigan State University.  For almost twenty-five years they have been growing twelve populations of Escherichia coli in a glucose-limited minimal medium and transferring a sample of each population to a fresh flask every day and freezing samples periodically for later analysis.  They have now propagated these bacteria for more than 40,000 generations. 

Under the well-aerated conditions of these cultures, E. coli cannot normally utilize the substantial amount of citrate in the medium as a carbon source.  However, mutation to a Cit+ phenotype did occur in one of the long-term populations after about 31,000 generations.  In a Nature paper published last month, Blount et al. (2012) thoroughly characterize the mutational steps required to achieve the Cit+ phenotype. (more…)

Parallel Evolution Guides Identification of Pathogenic Pathogen Mutations

The new tools for determining nucleotide sequences for whole genomes can sometimes present a problem of data analysis: How can mutations that influence important phenotypes be distinguished from mutations that may be of minimal or no impact on fitness, so-called passenger mutations that arise and persist primarily by chance and can greatly outnumber adaptive genetic variants?  Merely finding nucleotide substitutions or larger genomic differences in comparing independent isolates of a microbial pathogen does not automatically reveal which genetic variants are responsible for the medically-relevant differences in pathogen attributes.

Lieberman et al. (2011) have approached this problem by determining the whole genome sequences for 112 isolates of an opportunistic bacterial pathogen, Burkholderia dolosa, obtained from 14 cystic fibrosis (CF) patients, including the initial patient infected, who were all part of an epidemic of small scale in the Boston area.  A total of 39 individuals were infected in the course of the outbreak, and the patient samples were taken over a period of 16 years.  Bacterial samples were obtained primarily from the airways and from blood.  For these genome sequences, the average read depth was 37x, and the genomes were aligned based on a B. dolosa reference genome. (more…)