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In more distant comparisons, with longer ancestral divergence times, colinearity across orthologous regions appears to be much more rare than within the grasses.
Given the early availability of both the human and mouse genomes, initial efforts focused on human mouse pair-wise comparisons; but subsequent studies frequently used more distant comparisons such as human-fish to uncover functional non-coding elements with a higher stringency [15][16].
We may thus expect estimates of selective constraint to be lower for more distant comparisons.
We conducted analyses with and without these more distant comparisons (for details see supplementary material, Supplementary Material online).
As in other distance measures, this finds the most similar sequence fragments and is biased high, particularly for more distant comparisons.
More distant comparisons with mosquitoes, moths, beetles, and bees reveal hugely expanded and contracted lineages over time frames of 250 300 My (million years) (see, for example, [ 27]).
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With even more distant comparison to the eudicots, >220 million years of independent descent, only rare segments of genic colinearity are observed at either full genome or local genome scales [58].
In three of the four comparisons (human with tarsier, tree shrew, and opossum), significant bias was still identifiable between human and the more distant comparison species (supplementary table S1, Supplementary Material online).
Nevertheless, it is reassuring that our study of polymorphism and simulations of molecular evolution generally corroborate previous work based on more distant evolutionary comparisons.
However, the repeated observation of chimeras in our population data sets suggests that interparalog exchange may be more common than previously thought and that evidence for such nonallelic recombination may be obscured in more distant evolutionary comparisons by subsequent molecular events.
If dN/ dS was exceedingly high for an internal branch in the primate lineage (which is repeatedly included in all more distant pairwise comparisons), the observed negative correlation could in fact simply reflect the dilution of this high value with increasing branch length.
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