生命體的遺傳穩(wěn)定性在于基因組,,功能多樣性在于蛋白質(zhì)組。蛋白質(zhì)組是由若干蛋白質(zhì)所構(gòu)成的集合體,,其構(gòu)成原則即其豐度整體分布規(guī)律,,屬于重大理論問題,。賀福初院士所領(lǐng)導(dǎo)的軍事醫(yī)學(xué)科學(xué)院放射與輻射醫(yī)學(xué)研究所,、北京蛋白質(zhì)組研究中心,、蛋白質(zhì)組學(xué)國家重點實驗室及復(fù)旦大學(xué)生物醫(yī)學(xué)研究院科研團隊近來在多物種間揭示了蛋白質(zhì)豐度的整體分布與蛋白質(zhì)的進化、結(jié)構(gòu)和功能存在規(guī)律性的相關(guān),,其成果于2012年3月9日在線發(fā)表于PLoS ONE,。
自然界的各類現(xiàn)象都有其制約規(guī)律,生命體的表征也不例外,,蛋白質(zhì)作為生命活動的關(guān)鍵執(zhí)行者之一,,其重要性不言而喻。蛋白質(zhì)組學(xué)研究表明細(xì)胞內(nèi)不僅表達(dá)數(shù)千至數(shù)萬種蛋白質(zhì),,而且豐度差異高達(dá)6個數(shù)量級。如此巨大的差異是隨機產(chǎn)生的,,還是存在本質(zhì)的調(diào)節(jié)規(guī)律呢,?賀福初院士率領(lǐng)的科研團隊針對這一有趣的現(xiàn)象展開了探索。該團隊選取了在整個生命進化史中具有代表性的6個物種(大腸桿菌,、酵母,、線蟲、果蠅,、小鼠,、人)為研究對象,綜合它們的定量蛋白質(zhì)組數(shù)據(jù),,最終發(fā)現(xiàn)了存在于蛋白質(zhì)豐度整體分布的三個普適性規(guī)律:
1)在進化上,蛋白質(zhì)豐度與其起源時間和序列保守性呈正相關(guān),;2)從結(jié)構(gòu)角度,蛋白質(zhì)豐度與其結(jié)構(gòu)域數(shù)目呈負(fù)相關(guān),,而與其結(jié)構(gòu)域的覆蓋度呈正相關(guān),;3)蛋白質(zhì)的功能決定其豐度:參與基礎(chǔ)物質(zhì)流的蛋白質(zhì)其豐度高于調(diào)控精細(xì)信息流的蛋白質(zhì)。
蛋白質(zhì)豐度分布規(guī)律的揭示對深入認(rèn)識生命體的蛋白質(zhì)構(gòu)成原則具有重要的理論意義,,同時也為從海量數(shù)據(jù)到知識歸納提供了有效的實踐模式,。
自然科學(xué)的重要目標(biāo)是發(fā)現(xiàn)普遍規(guī)律與原理,其普遍的發(fā)展范式是:從數(shù)據(jù)的大量積累到經(jīng)驗性規(guī)律的不斷發(fā)現(xiàn),,繼而催生新的學(xué)說與理論。在生命科學(xué)領(lǐng)域,,近年來的組學(xué)研究導(dǎo)致了海量數(shù)據(jù)的“大爆炸”式積累,,如沒有理性條件下的系統(tǒng)化梳理,、歸納,、綜合(就像十九世紀(jì)的細(xì)胞論,、進化論,,二十世紀(jì)的基因論),,將不可避免地形成“災(zāi)難性”野性開采,。近20年前四條分子進化規(guī)律性的發(fā)現(xiàn)、5年前生物分子網(wǎng)絡(luò)組織規(guī)律的發(fā)現(xiàn),,生命體20種氨基酸的選擇對于細(xì)胞內(nèi)蛋白質(zhì)等電點分布一勞永逸的解決方案的報道,,以及不久前“促成生物學(xué)復(fù)雜性的蛋白質(zhì)結(jié)構(gòu)域特征因素規(guī)律性利用模式”的發(fā)現(xiàn),證明當(dāng)前生命科學(xué)領(lǐng)域急需系統(tǒng)化的數(shù)據(jù)挖掘,、并初步顯示出此類嘗試的有效性,。此文就是薈萃分析(meta-analysis)和深度挖掘方法系統(tǒng)應(yīng)用于蛋白組學(xué)數(shù)據(jù)的一個成功范例,為今后更加合理有效的利用組學(xué)數(shù)據(jù)進行理論生物學(xué)研究提供了方法和思路,。(生物谷 bioon.com)
doi:10.1371/journal.pone.0032423
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Regular Patterns for Proteome-Wide Distribution of Protein Abundance across Species
Fan Zhong, Dong Yang, Yunwei Hao, Chengzhao Lin, Ying Jiang, Wantao Ying, Songfeng Wu, Yunping Zhu1, Siqi Liu, Pengyuan Yang, Xiaohong Qian, Fuchu He
A proteome of the bio-entity, including cell, tissue, organ, and organism, consists of proteins of diverse abundance. The principle that determines the abundance of different proteins in a proteome is of fundamental significance for an understanding of the building blocks of the bio-entity. Here, we report three regular patterns in the proteome-wide distribution of protein abundance across species such as human, mouse, fly, worm, yeast, and bacteria: in most cases, protein abundance is positively correlated with the protein's origination time or sequence conservation during evolution; it is negatively correlated with the protein's domain number and positively correlated with domain coverage in protein structure, and the correlations became stronger during the course of evolution; protein abundance can be further stratified by the function of the protein, whereby proteins that act on material conversion and transportation (mass category) are more abundant than those that act on information modulation (information category). Thus, protein abundance is intrinsically related to the protein's inherent characters of evolution, structure, and function.