SUPPORTING INFORMATION: Contribution of selection for protein folding stability in shaping the patterns of polymorphisms in coding regions Adrian W.R. Serohijos and Eugene I. Shakhnovich† Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA USA 02138 † Correspondence: E.I.S. (
[email protected])
1
drift
Fitness, f
1
flux term toxicity term total fitness
selection
0.8 0.6 0.4 0.2 0 −10
−8
−6
−4
−2
ΔG (kcal/mol)
0
2
Supplementary Fig. S1. Organismal fitness f as a function of folding stability (Eqns. 1 to 3). The stability corresponding to mutation-selection balance is the same as indicated in fig. 4F.
2
Supplementary Fig. S2. Algorithm of the explicit in silico evolution of model organisms in the polyclonal that accounts for mutation, drift, and selection (Methods). Random mutations occur at the primary sequence and can affect the folding stability of the protein product.
3
Supplementary Fig. S3. Representative histories of mutations that fixed in the evolving population. Time window is as in figs. 1B-C and 2A-C. Mutations are colored according to their fitness effects.
4
A
Normalized per type of SNP
both non−syn syn
0.4
non-synonymous SNPs (27421)
0.4 0.2
0.2 0
Human Genome 0.6
Density
0.6
Density
B
Simulation
0
0.1
0.2
0.3
0.4
0.5
Minor Allele Frequency
0
0
0.1
0.2
0.3
0.4
0.5
Minor Allele Frequency
Supplementary Fig. S4. Distribution of minor allele frequencies in simulation (A) and in the coding region of the human genome (B).
5
All
Normalized Frequency
0.16
s>1/(2Ne)
|s|
