Since there is some uncertainty about the details of the microsatellite mutation process, we consider several plausible mutation schemes, and estimate the variance in mutation size simultaneously with the demographic parameters of interest.
To study the influence of the mutation process, we simulate the evolution of DNA sequences under nine different mutation biases with both transition-to-transversion ratios k = 2 and k = 20, Our model of protein evolution cannot be treated analytically, so that we have to study it using numerical simulations (see Fig. 1).
These two observations infirm the hypothesis of a transcription-induced GC-biased mutation process, and we are therefore confident that the observed correlation between optimal codon usage and expression rate is the consequence of selection for translational optimization.
Note, however, that the over-/under-representations can be made less marked by mutation processes lacking neighbor-base-dependence (we thank R.R. Hudson for pointing this out).
This model consists of a selection process, which depends on two hydrophobicity parameters that can be computed from protein sequences without any fit, and a mutation process for which we consider various models.
This apparent connection between MES-4 and the other MES complex in adult germ cells may be separable from PGC-specific processes, because mes-2 mutations do not affect the PGC processes we studied.
Following established methods16,27, we extracted 3 SC-specific signatures (Supplementary Fig. 3a) that represent the distinct mutation processes occurring during SC aging.
To probe whether the GOF mutations affected this process, we measured how an increase in the extracellular potassium concentration, [K+]O, from 2 to 90 mM affected pHO inhibition.
Also, we use the result that the number of mutations along a genealogical branch is Poisson distributed, and because we restrict our attention to neutral loci, we separate the mutation process from the genealogical process (Tavaré 1984; Hudson 1990).
Besides the reported effect of this mutation on the transfer process, we could not exclude that other functions could be affected as well, including at the transcriptional level.
