Both size and GC-content of minimal introns are selected in human populations

Abstract

Background: We previously have studied the insertion and deletion polymorphism by sequencing no more than one hundred introns in a mixed human population and found that the minimal introns tended to maintain length at an optimal size. Here we analyzed re-sequenced 179 individual genomes (from African, European, and Asian populations) from the data released by the 1000 Genome Project to study the size dynamics of minimal introns.

Principal findings: We not only confirmed that minimal introns in human populations are selected but also found two major effects in minimal intron evolution: (i) Size-effect: minimal introns longer than an optimal size (87 nt) tend to have a higher ratio of deletion to insertion than those that are shorter than the optimal size; (ii) GC-effect: minimal introns with lower GC content tend to be more frequently deleted than those with higher GC content. The GC-effect results in a higher GC content in minimal introns than their flanking exons as opposed to larger introns (≥125 nt) that always have a lower GC content than that of their flanking exons. We also observed that the two effects are distinguishable but not completely separable within and between populations.

Conclusions: We validated the unique mutation dynamics of minimal introns in keeping their near-optimal size and GC content, and our observations suggest potentially important functions of human minimal introns in transcript processing and gene regulation.

Figure 1. Estimation of key parameters.

The distributions of derived allele frequency or DAF (A) and GC content (B) of minimal introns among the three studied populations: Africans (YRI), Europeans (CEU), and Asians (JPTCHB). The dashed lines divide the thresholds for DAF (A) and intron GC content (B).

Figure 2. Indel counts and ratios.

RDI (A, B, C), insertions (D, E, F) and deletions per intron length (G, H, I) in different minimal intron size intervals of the three populations (DAF <0.1).

Figure 3. Relationship between GC content and intron size.

GC contents in three size intervals from the three populations (DAF <0.1): YRI (A), CEU (B), and JPTCHB (C) as well as the combined data (all introns; D). The horizontal lines in the boxplots indicate the upper, the median, and the lower quartiles (from the top to the bottom).