Both Size and GC-Content of Minimal Introns Are Selected in Human Populations

Abstract

BackgroundWe 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 FindingsWe 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.ConclusionsWe 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.

Intron evolution in Neurospora: the role of mutational bias and selection

“…First, the data from this study indicate that intron length is not a major factor determining intron dynamics in Neurospora (Figs. 4, 8), which is in contrast to other studies (of humans and Drosophila) in which selection is involved in shaping intron length distribution (Coulombe-Huntington and Majewski 2007b;Wang and Yu 2011;Leushkin et al 2013). Furthermore, as for the majority of other organisms that have been analyzed to date (Denoeud et al 2010;Rogozin et al 2012), we found a strong phase 0 bias of intron position in Neurospora.…”

Systematic analysis of intron size and abundance parameters in diverse lineages

“…First, comparative studies of splicing machineries have pointed out the tempo-spatial features of the different types of introns that all have unique characteristics as we have discussed above in this article and previously elsewhere [6]. Second, evolutionary studies have proven that minimal introns are selected through negative selections on minimal-intron-containing genes and have special sequence contexts in human populations [8,11]. The original design of these experiments is to investigate whether the intron size constraint of human minimal introns is selected in a human population but it has also revealed sequence context relevance [38,11].…”

“…Second, evolutionary studies have proven that minimal introns are selected through negative selections on minimal-intron-containing genes and have special sequence contexts in human populations [8,11]. The original design of these experiments is to investigate whether the intron size constraint of human minimal introns is selected in a human population but it has also revealed sequence context relevance [38,11]. It is not difficult to extend the conclusion in any other population data beyond mammals.…”

“…The number and size parameters by and large reflect the nature and efficiency of the intron splicing machinery of particular species or lineages [5][6][7][8][9]. The context parameters are most complicated, concerning the sequence content and context of nucleotide composition (such as GC and purine contents), transposable elements, and functional elements (such as splicing enhancers and the branch point) [10][11][12]. There are at least three possibilities for the existence and the absence of introns in eukaryotic genes: intronless (no intron), small introns in fixed sizes, and large introns in variable sizes.…”

Stabilizing Selection, Purifying Selection, and Mutational Bias in Finite Populations

“…This has led to the proposal that species with a low effective population size (N e ), in which selection is relatively ineffective in relation to genetic drift and mutation (Wright 1931;, are more likely than species with a high N e to evolve selectively disadvantageous properties, such as lower codon usage bias, larger genome size, and a higher mutation rate (Lynch 2002(Lynch , 2007(Lynch , 2011Sung et al 2012). But there is no a priori reason to exclude the possibility that at least some genomic traits are subject to stabilizing selection rather than purifying selection, so that individuals with extreme values of the trait are at a selective disadvantage compared with those with intermediate values (Kimura 1981;Johnson 1999;Parsch 2003;Wang and Yu 2011).Evidence that quantitative traits can be subject to stabilizing selection started to accumulate over a century ago (Bumpus 1899;Weldon 1901;Di Cesnola 1907). Subsequently, Fisher (1930b, pp.…”