“人類基因組計劃”顯示,，人類30億個堿基對中只有很少一部分用于編碼蛋白質(zhì),。那么人類基因組剩余的部分在起著什么作用？它們是否只是之前遺傳事件的殘余,？
美國科學家近日研究發(fā)現(xiàn),，遺傳信息轉(zhuǎn)變?yōu)榈鞍踪|(zhì)的過程中會留下遺傳“指紋”，這些“指紋”甚至會出現(xiàn)在未參與蛋白編碼過程的序列中,。研究人員估計這些“指紋”至少影響到了三分之一的基因組,，這表明雖然大部分DNA不參與編碼蛋白，但是它們對在進化期間保持持續(xù)性具有重要的生物學作用,。相關論文4月7日在線發(fā)表于美國《國家科學院院刊》（PNAS）上,。
生物學家認為，不同物種的基因組有些相關序列相差很大,，這是進化導致的突變所致,；而有些相關序列所含基因相似，這些序列稱為保守序列（conserved sequences）,，這些序列中基因的突變會使物種無法存活。生物學家因此將保守序列視為生物學重要性的標記,。
要檢測保守性,，研究人員需要在兩個物種中找到匹配的序列。這對編碼序列來說相對簡單,，而對非編碼序列來說則要困難許多,。即使在一個基因之內(nèi)，編碼目標蛋白的序列也通常會點綴著“內(nèi)含子”（introns）,，這些內(nèi)含子在蛋白質(zhì)形成之前會被切除下來,。
之前，科學家猜測內(nèi)含子中的突變不會影響最后的蛋白質(zhì),，所以它們就簡單地積累起來,。而在最新的研究中，美國冷泉港實驗室和芝加哥大學的研究人員發(fā)現(xiàn),，即使在這些區(qū)域,，進化也會拒絕一些類型的突變。研究負責人,、冷泉港實驗室教授Michael Zhang認為,，雖然選擇是微弱的,，但就對存活的影響來說，“內(nèi)含子不是中立的”,。
接下來的研究發(fā)現(xiàn),，必須有某種信號序列（signal sequences）出現(xiàn)在內(nèi)含子中，它才能被很好地剪切,，否則會帶來潛在的致命效果,。其它一些序列同樣得以保存在保留區(qū)域內(nèi)。
研究人員還發(fā)現(xiàn)了內(nèi)含子和編碼區(qū)對不同堿基的偏愛,。這些區(qū)域一共構成三分之一多的基因組,，經(jīng)歷著進化的選擇壓力。這一發(fā)現(xiàn)支持了其他一些研究的結果,，即雖然大多數(shù)DNA不編碼蛋白質(zhì),，它們中的大部分卻具有重要的生物學意義。
除了證明了剪接怎樣影響遺傳進化之外,，此次研究還確定了一些可能的信號序列,，其中一些為過去已知，另一些則是全新發(fā)現(xiàn),。論文合作者,、冷泉港實驗室教授Adrian Krainer說：“令人激動的是，將來要用實驗方法檢測這些預測元素是否是真的,。”（科學網(wǎng) 梅進/編譯）
生物谷推薦原始出處：
（PNAS）,，doi：10.1073/pnas.0801692105，Chaolin Zhang,，Michael Q. Zhang
RNA landscape of evolution for optimal exon and intron discrimination
Chaolin Zhang*,, Wen-Hsiung Li, Adrian R. Krainer*, and Michael Q. Zhang*,
*Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724; Department of Biomedical Engineering, State University of New York, Stony Brook, NY 11794; and Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637
Contributed by Wen-Hsiung Li, February 20, 2008 (sent for review January 8, 2008)
Abstract
Accurate pre-mRNA splicing requires primary splicing signals, including the splice sites, a polypyrimidine tract, and a branch site, other splicing-regulatory elements (SREs). The SREs include exonic splicing enhancers (ESEs), exonic splicing silencers (ESSs), intronic splicing enhancers (ISEs), and intronic splicing silencers (ISSs), which are typically located near the splice sites. However, it is unclear to what extent splicing-driven selective pressure constrains exonic and intronic sequences, especially those distant from the splice sites. Here, we studied the distribution of SREs in human genes in terms of DNA strand-asymmetry patterns. Under a neutral evolution model, each mononucleotide or oligonucleotide should have a symmetric (Chargaff's second parity rule), or weakly asymmetric yet uniform, distribution throughout a pre-mRNA transcript. However, we found that large sets of unbiased, experimentally determined SREs show a distinct strand-asymmetry pattern that is inconsistent with the neutral evolution model, and reflects their functional roles in splicing. ESEs are selected in exons and depleted in introns and vice versa for ESSs. Surprisingly, this trend extends into deep intronic sequences, accounting for one third of the genome. Selection is detectable even at the mononucleotide level, so that the asymmetric base compositions of exons and introns are predictive of ESEs and ESSs. We developed a method that effectively predicts SREs based on strand asymmetry, expanding the current catalog of SREs. Our results suggest that human genes have been optimized for exon and intron discrimination through an RNA landscape shaped during evolution.
