Its well-known that amino acids aren't necessarily well-conserved in homologous proteins, but function will remain. Obviously some amino acids can easily substitute in for others to fulfill some structure or charge function. So what happens when a SNP comes along and alter an amino acid? Usually, nothing, or at most a slight decrease in stability.
The authors scanned the human genome of a small sample of African and European Americans, looking for SNPs, allele frequency, and the amount of change each SNP may cause. They found that many nonsynonymous mutations are neutral (27-29%), a large amount are slightly deleterious (30-42%), and the rest are highly deleterious or lethal. Most of the highly deleterious alleles were present in alleles that were less than 5% of sampled alleles at that locus. Additionally, the cumulative affect of benign mutations greatly outweighed the effect of harmful mutations. The affect of SNPs was measured using PolyPhen, a program that characterized the SNP as benign, possibly damaging, and probably damaging based on its conservation and amino acid change; ‘damaging’ only referring to protein structure not organisms’ fitness. Furthermore, comparing to an outgroup of chimpanzees, 10-20% of SNPs were deemed fixed by positive selection.
Allele frequency on x-axis
Red: strongly deleterious
Orange: moderately
Yellow: weakly
Green: nearly neutral
Blue: neutral
White: beneficial
Other notes:
-around half of nonsynonymous mutations are strongly or mildly deleterious
-most segregating variation above 5% frequency in the population is predicted to be nearly neutral, with higher proportion of neutral variation as the allele frequency increases
-15,916 benign; 4,199 possibly damaging; 2,646 probably damaging SNPs from PolyPhen
-estimated 5% of benign, 27% of possibly, and 35% of probably damaging were fixed through positive selection
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