Compared with the neutral reference, both proximal and tele-enhancers evolved under a significant negative selection pressure (P < 6 × 10−23, Fisher's exact test, Table 1).
K a /K s ratios < 1 indicate that <span class="lh">a sequence is under negative selection, K a /K s ratios close to 1 imply that the sequence is undergoing drift, and K a /K s ratios > 1 suggest that the sequence is under positive selection.
Phenotypic regression of morphological, behavioral, or physiological traits is a common process contributing to evolutionary trait dynamics (Fong and Kane 1995; Porter and Crandall 2003) that is frequently observed when a trait is under negative selection or when bearing a trait is selectively neutral (Lahti et al. 2009).
A portion of the C-terminal transactivation domain in FOXO4 and the entire transactivation domain in FOXO1a was under strong negative selection, therefore a C-terminal transactivation domain consisting of the negatively selected residues (sites 389 428 in Figure 2D, residues 605 673 in FOXO3a) may be predicted in FOXO3a.
LRT is a likelihood ratio test comparing the probability that a codon has evolved under negative selection to a model in which the codon has evolved neutrally, where rates of synonymous and nonsynonymous substitutions are equal.
One prediction from coupling between enzymes in a pathway is that when a pathway is under negative selection (or other types of selection), that the selective pressure on amino acid change in an individual protein will relate to the sensitivity of pathway function to perturbation of each individual enzyme based upon amino acid changes.
This is expected for a gene under strong negative selection and is mirrored in the finding of synonymous mutations at 17 of 22 segregating sites.
Increased d N /d S among conspecifics (or among closely related sequences/species) has been observed in other taxa, and a variety of hypotheses has been suggested to interpret these results under a regime of negative selection: balancing selection, variable population sizes, variable mutation rates, relaxed selective constraints and/or the prevalence of slightly deleterious mutations [ 19, 20].
We also conducted simulations under a scenario of negative selection acting on TE insertions that arose from a single recent burst of transposition.
Since the scenario we have simulated seems biologically reasonable, i.e. a combination of some sites under very strong negative selection, some sites under moderate negative selection, and a small proportion of sites evolving neutrally, we believe that evidence of adaptive evolution obtained with the M7-M8 LRT alone should be treated with caution.
