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…)

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…)

Evolutionary and Ecological Factors in Influenza A Virus Spread

In the May 26 (2011) issue of Nature, Vijaykrishna et al. address patterns of evolution and transmission exhibited by swine influenza A viruses (SwIV) isolated from pigs beings slaughtered in Hong Kong between May 1998 and January 2010.  Although the focus of the study is on viruses that circulate in swine, this study is relevant to human medicine and public health because these viruses can serve as the ancestors of viruses that infect people.  (more…)

A Genomic Perspective on Pathogen Adaptation to Antibiotics and Vaccines

Among human pathogens, Streptococcus pneumoniae holds an especially prominent place in the history of biomedical investigation.  Griffith (1928) described the transforming principle, a soluble substance released by dead, virulent pneumococci that could render living avirulent pneumococci able to effectively kill a mouse.  Oswald Avery’s commitment to curing pneumococcal pneumonia (http://profiles.nlm.nih.gov/ps/retrieve/Narrative/CC/p-nid/37) led him and his collaborators to determine that the pneumococcal transforming principle was DNA (Avery et al., 1944).  It was also Avery’s and his collaborators’ work on pneumococci that provided some of the first insights into the chemical nature of most bacterial capsules. (more…)