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Alanine mutation at other residues of the β7 β8 loop did not affect either RT stability or virus infectivity significantly.
The reason could attribute to smaller effect sizes of this mutation at other ages that had low power to uncover it.
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The effects of mutations at other active site residues are however more variable.
Also, second-site mutations at other genes can act as suppressors, restoring wild type function.
In a changing environment, the short-term advantage of producing beneficial mutations at other loci can allow mut-T to spread by hitch-hiking, despite its long-term disadvantages.
In contrast, many mutations at other positions in TM14 exhibited reduced substrate-binding affinities.
Non-synonymous mutations at other residues, and in particular 57 and 61, were not observed.
In our analysis it appears that selection at one locus does not have any affect on the distribution of mutations at other loci.
This is in line with the theoretical prediction that genes that are better able to buffer genetic mutations at other loci will evolve higher genetic robustness.
Mutations at other positions, possibly followed by subsequent mutations elsewhere in the protein either preserved (or restored) the original protein function or gave rise to a newly acquired one.
Second, restoration of normal rates of growth in resistant strains is more often attributable to compensatory mutations at other loci, rather than to back-mutation, thus preserving the resistance trait in the bacterial population [6].
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