As shown in figure 3 B , values of P 50(KCl + IHP) for the SIAI, SVAV, and SIVI genotypes fell well below the lower 95% confidence limit of the ancestral, high-affinity GVAI genotype, and an additional double-mutant genotype, GIAV, exhibited a marginally significant reduction in P 50(KCl + IHP) below this same threshold.
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Stability-Mediated Epistasis Restricts Accessible Mutational Pathways in the Functional Evolution of Avian Hemoglobin.
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