pleiotropy - senecio7の日記

Razeto-Barry P, Díaz J, Cotras D & Vásquez RA 2011 Molecular evolution, mutation size and gene pleiotropy: a geometric reexamination. Genetics 187:877-885.

Gu (2007a,b) used a bottom–up approach for the generation of mutational random vectors (Poon and Otto 2000)
the magnitude of vectors increases as the number of dimensions increases (Appendix 2 of Orr 2000)
the previous approaches cannot distinguish separately the effect of mutation size and the effect of pleiotropy in the substitution rate of a gene
to differentiate between the influence of mutation size and pleiotropy, it is critical to use a top–down approach (Poon and Otto 2000)
our second improvement was to specify explicitly the magnitude distribution of the vector
the magnitude distribution of vector components along each axis is left unspecified
a change in the number of dimensions does not affect the magnitude of mutational effects, guaranteeing that gene pleiotropy is not correlated with mutation size

the distribution of magnitude used was uniform, implying that in each axis the magnitude distribution of vector components is leptokurtic

we found that gene pleiotropy, i.e., the number of orthogonal molecular phenotypes affected by the mutations in a protein, does not affect the rate of substitutions in a nearly neutral, environmentally stable condition
this result contrasts with the fact that in the FGM the probability that a mutation of a given phenotypic size is advantageous decreases with the number of dimensions, and the probability that it is deleterious increases
in the balanced steady state, this fact affects only the mean equilibrium fitness
when the equilibrium is attained, the rate of substitutions is not affected by the number of dimensions
protein evolution is not affected by gene pleiotropy
while the equilibrium fitness is lower for higher dimensions, the number of advantageous mutations increases since the population is further away from the optimum
the effect of the dimensionality is compensated by the effect of the distance from the optimum

in our model we differentiated the effect of gene pleiotropy and the average size of the mutational effects such that gene pleiotropy was not correlated with the average mutational size

Gu (2007a,b) and Su et al. (2010) theoretically found a strong negative relationship between evolutionary rate and gene pleiotropy
these findings can be explained by their bottom–up approach to the random vector generation
the distribution and magnitude of mutational effects are specified for each axis and the total magnitude of mutation is left unspecified
under the bottom–up approach the magnitude of vectors increases as the number of dimensions increase
in Gu's model higher pleiotropy decreases the evolutionary rate simply because pleiotropy increases the size of mutations
(other criticisms applicable to the approach used by Gu 2007a,b can be found in Appendix 2 of Orr 2000)