Increased Substitution Rates in DNA Surrounding Low-Complexity Regions

Abstract

<p>Previous studies have found that DNA flanking low-complexity regions (LCRs) have an increased substitution rate. Here, the substitution rate was confirmed to increase in the vicinity of LCRs in several primate species, including humans. This effect was also found within human sequences from the 1000 Genomes Project. A strong correlation was found between average substitution rate per site and distance from the LCR, as well as between the proportion of genes with gaps in the alignment at each site and distance from the LCR. Along with substitution rates, dN/dS ratios were also determined for each site, and the proportion of sites undergoing negative selection was found to have a negative relationship with distance from the LCR.</p> <p>Low-complexity regions in proteins often form and extend through the gain or loss of repeated units, a process that is dependent on the presence of a relatively pure string of repeats. Any interruption should disrupt the mechanisms of LCR extension and contraction, inhibiting LCR formation. Despite this, several examples have been found of LCR-coding DNA which are interrupted by introns. While many of these LCRs may be the result of two shorter LCRs forming on opposite sides of an intron, shuffling the order of exons showed that more intron-interrupted LCRs exist than would be expected to occur randomly. Another possible explanation for this phenomenon is the apparent movement of either the LCRs or introns, possibly through recombination or the appearance of new splice sites through the gain of repeat units.</p>