Like most point mutations, the majority are probably mildly deleterious.
Alternatively, these observed sequence level changes could be neutral or possibly even mildly deleterious.
Bustamante et al., [24] suggests that this may indicate an excess of mildly deleterious variation possibly due to balancing selection.
These simulations also allowed us to ask at what rate mildly deleterious alleles are lost between BY and RM.
More generally, our results confirm theoretical predictions that mildly deleterious regulatory QTL segregate in natural populations [42] and raise the possibility that these polymorphisms contribute to phenotypic diversity.
Thus, for the moment it cannot be ruled out that T9205C is a benign or mildly deleterious variant, despite the considerable extension of the amino acid chain.
Hence, rare mutations represent a greater fraction of new and mildly deleterious mutations, whereas common ones represent a greater fraction of ancient and neutral mutations.
We demonstrate that purifying selection against mildly deleterious alleles is the dominant force governing cis-regulatory evolution in S. cerevisiae and estimate the strength of selection.
Specifically, the compensation-draft feedback process postulates that fixation of a mildly deleterious mutation favors compensatory mutations within the same or interacting polypeptides, which in turn can result in fixation of new mildly deleterious mutations by genetic draft due to the linked, non-recombining genes in mitochondrial DNA [80].
Alternative explanation, concerning natural selection, would be that the small historical population size of humans has reduced the efficiency of purifying selection, which enabled the mildly deleterious synonymous sites to escape the purifying selection among humans but not in chimpanzees.
These shallower genealogies imply approximately half the level neutral variation, and hence a higher ratio of mildly deleterious to neutral changes at these loci as evidenced by the significantly elevated rare derived allele skew in non-synonymous changes.
