Either way, the establishment of alternative gene content motifs in both the centromeric and telomeric regions, provided the basic structure within which increasingly elaborate A and B motifs could evolve.
In general, a motif's correlation to recombination rate was influenced by its relative GC content, with high GC content motifs correlating positively to recombination rate.
These subtle and complex differences are presumably obscured by the motif derivation process, which tends to produce degenerate (i.e., low information content) motifs for most of these TFs.
As part of that expansion both 2DS4 and 2DL5 were moved into the telomeric region, but as part of different and mutually exclusive gene-content motifs.
Dividing the KIR haplotypes into centromeric and telomeric regions separated by the 3DP1-2DL4 framework [33], showed that the seven gene content KIR haplotypes are all combinations of four centromeric and two telomeric gene-content motifs (Figure 1).
Phylogenetic analysis and divergence time estimates, point to the centromeric gene-content motifs that distinguish A and B haplotypes having emerged ∼6 million years ago, contemporaneously with the separation of human and chimpanzee ancestors.
This unique sequence has been the site for events of reciprocal recombination that allowed centromeric and telomeric gene-content motifs to reassort in different combinations and form new variant KIR haplotypes [34], [46].
The gene-content, and allele-content motifs contained in the centromeric and telomeric regions of these 27 haplotypes are likely to account for many common haplotypes in many human populations, and should provide a strong base from which to investigate the rarer and more population-specific haplotypes.
Table 2 shows the means and standard deviations of log10 for these intervals and for the seven predictor variables defined for each inter-SNP interval: length, regional recombination rate, G+C content, "core" motif count, "extended" motif count, hot spot presence, and AluY presence (as detailed in Methods).
