near neutrality

Gu X 2007 Stabilizing selection of protein function and distribution of selection coefficient among sites. Genetica 130:93-97.

  • the evolutionary conservation of protein function can be viewed as a set of several (K) molecular phenotypes that are constrained by independent stabilizing selections
  • for simplicity, we assume σ2w is the same for all molecular phenotypes
  • independent of other parameters, the gamma shape parameter of ƒ(S) or ƒ(s) is K / 2
  • indicating an important role of K in the nearly-neutral model
  • the distribution of fitness effects for deleterious mutations is highly leptokurtic
  • more recent work with experimental populations of bacteria has confirmed that the distribution is leptokurtic
  • if this is the general case, one may speculate that the gamma shape parameter of ƒ(S) is not very larger than 1
  • roughly K ≤ 2
  • Ohta (1977) was the first to investigate the population genetical consequences of very slightly deleterious mutations by assuming that selection coefficients against the new mutations follow an exponential distribution, which is equivalent to K = 2 in Eq. 8
  • assuming that the generation time (g) is roughly inversely proportional to Ne, Ohta (1977) demonstrated a constant evolutionary rate (molecular clock) with respect to years rather than to generations
  • Kimura (1979, 1983) criticized that Ohta's (1977) model has drawback
  • it cannot accommodate enough mutations that behave effectively as neutral when the population size gets large
  • instead, Kimura (1979) proposed the model of effective neutral mutations, which assumes that the selection coefficients among mutations follow a gamma distribution characterized by the shape parameter β
  • Ohta's (1977) model is the special case of β = 1
  • Kimura (1979) regarded β < 1 as representing the degree of physiological homeostasis that should be species-soecific
  • up to present there is no supporting empirical evidence
  • our analysis has provided an interpretation that differs dramatically from Kimura's (1979) original view
  • we have β = K / 2
  • the fitness function follows a Gaussian curve
  • there was no much evidence to expect this form
  • Eyre-Walker et al. (personal communication) has estimated the shape parameter of 0.23