Fourth, and perhaps most strikingly, a comparison of the NIRV sequences from different fungal species shows that their ratio of non-synonymous to synonymous nucleotide substitutions (Kn/Ks) is significantly less than 1 which is evidence of evolution under the pressure of purifying selection [ 14] (although, judging from the Ka/Ks values, that pressure is rather weak).
However, the time frame in which some of the therapy-resistant diseases arise cannot solely be explained by evolution under selective pressure.
We showed that divergence patterns in nuclear-encoded tRNA molecules of vertebrate and drosophilid species follow general theoretical predictions for sequence evolution under mutational pressure.
Understanding the underlying mechanisms of antigenic diversity and cyclical epidemics will provide theoretical bases for their evolution under selective pressure such as the replacement of strains and the emergence of resistance strains under pharmacological control measures [ 25].
The mechanism of acquired targeted therapy resistance – mutations in the target and activation of the same or parallel pathways of the target – is widely accepted as via molecular evolution under selective pressure in a Darwinian sense.
One hallmark of such a relationship between a virus and its host is the evolution, under selective pressure to resist infection, of host genes encoding proviral and antiviral factors.
We show that patterns of nucleotide variation for the two classes of sites are explained well by Kimura's one- and two-locus models of sequence evolution under mutational pressure.
Despite over 40 years of evolution under immune pressure that should promote antigenic diversification, H3N2 influenza viruses exhibit very limited genetic and antigenic diversity at any one time, instead being characterised by the presence of only one dominant circulating strain.
Our data reveal that resistance in this patient was not mediated by acquired mutations or sub-clonal evolution under selection pressure exerted by treatment, but by a combination of pre-existing mutations in two genes that activate at least two pro-growth/pro-survival pathways.
The proposed RT-PCR protocol and subsequent analysis pipeline for influenza viruses is widely applicable, e.g. to study vaccine composition, analyze virus evolution under selection pressure, monitor mutations associated with antiviral resistance, and assemble the reference genome of new viral isolates.
