This suggests that differences in levels of selective constraint play a major role in causing the differences between the two sets of genes, with the fast-evolving genes being under weaker constraints with respect to purifying selection.
We found above that genes harboring SCPs are likely to be under weak functional constraint.
Only a minority of residues may be under weak or no constraint, for example those that cause silent changes in lowly expressed proteins.
Therefore, our study compared the "proximal promoter" region, which is defined as the 200-bp region upstream of the TSS and is expected to contain more TFBSs, with the "distal promoter" region, which is defined as the intergenic region between 201 and 400 bp upstream of the TSS and is expected to be under weaker selective constraint.
A possible hypothesis based on these trends is that expensive amino acids are only used for specific structural or functional roles and are therefore conserved, while cheaper amino acids may be under weaker structural or functional constraints and more likely to be substituted.
Together, these observations are consistent with the hypothesis that genes carrying these subsets of SCPs are under weaker selective constraint than other genes.
Within the URA1 gene family we found that both the laboratory S288c strain and the VL3 wine production strain were under weaker selective constraint than both the wine strain AWRI796 and the human pathogen strain YJM789.
Regions evolving under weak constraint, however, could often be missed by current approaches as they will not always show the expected signature of conservation.
Using single nucleotide polymorphisms (SNPs) from human and yeast populations, and polarized distribution of fitness effect (DFE) analyses, we validate previous reports that amino acid replacements are under negative selection in yeast and humans, although disordered regions appear to be under moderately weaker constraints of selection compared with folding protein regions.
The limitations of conservation analysis presented here spotlight the need for more accurate inference methods in comparative genomics in order to also capture regions evolving under weak constraint.
