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COMPLEMENTATION. "The efficiency of purifying (or negative) selection is the product of effective population size and the average mutational fitness effect(s). In large populations, strong selection will quickly purge mutants with lower fitness. Larger population sizes may also result in higher multiplicities of infection, where a given cell supports replication of at least two different genomes. Here, genetic complementation can increase the robustness of the viral population." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

POPULATION SHIELD. "Most mutations have deleterious effects on viral fitness. Tolerance to mutational load determines the nature and extent of genetic diversity that can be maintained in the population. Thus, viral population diversity results from both the generation of mutations and the tolerance to them; these two factors together drive adaptation and virus evolution." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

LOW FIDELITY. "The focus on mutation as a driving force in viral evolution has tended to overlook the tremendous cost of low replicative fidelity." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

DIAGNOSTIC SOLUTION. "To overcome this limitation an experimental approach was developed that dramatically reduces sequencing errors.The basic premise of this method, called Circular Sequencing (or CirSeq). Using this approach, we are now able to estimate changes in mutation frequency of variants that exist in the population at very low levels. This opens an opportunity to determine fitness landscape at single nucleotide resolution." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

DIAGNOSTIC CHALLENGES. "Characterizing the genetic structure of virus populations remains a fundamental challenge. High-throughput sequencing technologies are capable of generating very large datasets; but distinguishing true genetic variation from sequencing error remains a central problem due to the high average sequencing error rates for NGS and given that even small error probabilities result in a significant number of sequencing errors." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

PROGNOSTIC FITNESS. "Translated into clinical practice, it means that the evolutionary history of HCV in infected patients may influence the response to treatments. In particular, long-term replication of HCV during prolonged chronicity may increase viral fitness to the detriment of treatment efficacy, as observed in clinical practice. These observations render essential to develop methods to define fitness values in vivo and to explore the fitness landscape in viral populations." http://www.sciencedirect.com/science/article/pii/S0042682215001580 View in LinkedIn

TRANSITION TO LIVING MOLECULES. "However, once informational macromolecules are given the opportunity to inherit profitable variation through self-sustained Darwinian evolution, they just may take on a life of their own." Read very carefully. http://www.cfr.org/united-states/biologys-brave-new-world/p31894 View in LinkedIn

ENGINE OF INNOVATION. "Life on Earth ... has demonstrated extraordinary resiliency and inventiveness in adapting to highly disparate niches. Perhaps the most significant invention of life is a genetic system that has an extensible capacity for inventiveness, something that likely will not be achieved soon for synthetic biological systems." http://www.cfr.org/united-states/biologys-brave-new-world/p31894 View in LinkedIn

DISRUPTIVE EFFICIENCIES. "In the past 25 years, modern society has seen many disruptive innovations, most of which have been based on a single platform: the internet. The key feature of most disruptive innovations is their ability to exploit and eliminate inefficiencies in existing systems. The connectedness enabled by the internet has allowed companies across a range of industries to replace traditional, capital-intensive approaches with new ways of doing business." https://lnkd.in/dPP5UrP View in LinkedIn

SO ENDS these two weekends looking at RNA virus quasispecies. No other creature on this planet has such a high rate of mutation, and viruses are the largest pool of genetic diversity; they actively exchange genes between them and with their hosts. These shimmering and shape-shifting populations have played a key role in evolution, and equally, when the symbiotic spectrum is at the extreme, represent diseases that can be very hard to treat. That said, the vast majority of viruses are benign, and co-exist happily with their host ecosystems. View in LinkedIn