近日，在中國科學(xué)院北京基因組研究所副所長,、中國科學(xué)院基因組科學(xué)與信息重點(diǎn)實(shí)驗(yàn)室主任于軍研究員的指導(dǎo)下,，該重點(diǎn)實(shí)驗(yàn)室博士生王大鵬通過對(duì)人類千人基因組計(jì)劃數(shù)據(jù)的比較分析，進(jìn)一步證實(shí)了兩種DNA組分特殊效應(yīng)在人類基因組中的存在,，使該研究組延續(xù)十幾年的小內(nèi)含子基本功能和進(jìn)化機(jī)制研究獲新進(jìn)展,。相關(guān)學(xué)術(shù)論文在PLoS ONE雜志發(fā)表，并且被GenomeWeb網(wǎng)站推薦為“每日精選”,。
內(nèi)含子是真核基因組的重要和必需組成部分,，并且它在mRNA的加工、選擇性剪接和核外運(yùn)輸?shù)冗^程中發(fā)揮著精確且復(fù)雜的作用,。在基因組進(jìn)化研究中,，盡管內(nèi)含子并沒有像編碼區(qū)域一樣受到足夠的重視，但越來越多證據(jù)表明內(nèi)含子和它們的序列受到潛在功能相關(guān)的自然選擇作用,。
此次博士生王大鵬等的發(fā)現(xiàn)：出現(xiàn)在長度范圍為88-124nt上的小內(nèi)含子的刪除/插入比值要高于50-86nt,；另外，出現(xiàn)在GC含量（鳥嘌呤和胞嘧啶所占的比例）小于65%的小內(nèi)含子上的刪除/插入比值要高于GC含量大于65%的,。進(jìn)一步發(fā)現(xiàn),，這兩種效應(yīng)可以在某種程度上得以區(qū)分但是并不能完全獨(dú)立存在。這可能是因?yàn)橐恍〨C富集的小內(nèi)含子在長度上受到較弱的純化選擇,，而在GC含量方面受到了較強(qiáng)的正選擇,。
該研究結(jié)果表明，在不同人類群體中,，小內(nèi)含子的長度和GC含量都受到某種自然選擇（適應(yīng)性選擇或者負(fù)選擇）的作用而保持在最適值附近,。這些結(jié)果為“突變力”模型提供了證據(jù)：偏離最適合長度值的小內(nèi)含子更容易發(fā)生插入刪除突變。區(qū)別于在果蠅中發(fā)現(xiàn)的“選擇力”模型,，該研究揭示了脊椎動(dòng)物這一分支中小內(nèi)含子的進(jìn)化動(dòng)力學(xué)特性,，強(qiáng)調(diào)了小內(nèi)含子的潛在的功能重要性，為后續(xù)的各物種小內(nèi)含子功能研究的實(shí)驗(yàn)和生物信息研究奠定了理論基礎(chǔ),。（生物谷Bioon.com）
生物谷推薦原文出處：
PLoS ONE 6(3): e17945. doi:10.1371/journal.pone.0017945
Both Size and GC-Content of Minimal Introns Are Selected in Human Populations
Dapeng Wang1,2, Jun Yu1*
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.
