Table 2. Estimates of the scaled selection parameter γ(=2N_Cs) for conservative, moderate, and radical nonsynonymous changes, as defined by different measures of amino acid exchangeability, and for nonsynonymous mutations categorized as “benign,” “possibly damaging,” or “probably damaging” by the polyphen program, which uses site-specific structural and phylogenetic information.

		Conservative		Moderate		Radical
Exchangeability measure	Ref.	Range		Range		Range
Physicochemical measures
Miyata metric	16	x ≤ 0.89	-5.71*	0.89 < x ≤ 1.85	-8.45*	x > 1.85	-14.06*
Grantham's distance	17	x ≤ 44	-7.48*	44 < x ≤ 82	-7.77*	x > 82	-12.04*
Experimental measures
Experimental exchangeability	20	x > 0.354	-6.35*	0.256 < x ≤ 0.354	-8.79*	x ≤ 0.256	-12.15*
General measures based on structural models
Protein stability matrix	21	x > 0.210	-8.19*	0.030 < x ≤ 0.210	-8.55*	x ≤ 0.030	-10.15*
Phylogenetic measures
PAM-120	18	x > 1	-5.32	-1 < x ≤ 1	-8.35*	x ≤ -1	-12.76*
BLOSUM-45	19	x > 0	-8.41*	-1 < x ≤ 0	-3.96	x ≤ -1	-13.39*
BLOSUM-62	19	x > 0	-8.41*	-1 < x ≤ 0	-4.09	x ≤ -1	-12.75*
BLOSUM-80	19	x > 0	-8.46*	-2 < x ≤ 0	-4.49	x ≤ -2	-13.52*
Site-specific structural/phylogenetic measures
Polyphen	22	“Benign” (310 SNPs)	-6.072*	“Possibly damaging” (97 SNPs)	-11.732*	“Probably damaging” (56 SNPs)	-23.602*

Ranges define the values of the exchangeability measure, x, over which the category extends.

^*Categories for which a likelihood ratio test rejects neutrality (P < 0.01).