生物谷報(bào)道：Warwick大學(xué)研究人員最近揭開(kāi)了女性細(xì)胞在其兩條染色體之間隨機(jī)選擇的奧秘,。
男性細(xì)胞有X染色體和Y染色體,，女性細(xì)胞有兩條X染色體,，意味著性別為女的受精卵在發(fā)育的早期階段需要沉默兩條X染色體中的一條,。這個(gè)過(guò)程非常關(guān)鍵,，出錯(cuò)會(huì)導(dǎo)致嚴(yán)重的遺傳疾病,。細(xì)胞中的兩條染色體都有自殺基因XIST,。XIST活化,，其所在的X染色體失活。研究人員詳細(xì)這種自殺基因是通過(guò)在其染色體位點(diǎn)上形成一個(gè)“蛋白栓”實(shí)現(xiàn)自我封閉的,，但不清楚這種過(guò)程在兩條染色體間隨機(jī)進(jìn)行的機(jī)制,。其實(shí)研究人員對(duì)這種隨機(jī)說(shuō)法非常不滿意，一直沒(méi)有中斷過(guò)尋找X染色體隨機(jī)失活的規(guī)律。
最近,，Warwick大學(xué)物理學(xué)家Mario Nicodemi率領(lǐng)的研究小組探清了這種隨機(jī)性發(fā)生的機(jī)制及其優(yōu)勢(shì),，不僅為研究少數(shù)婦女X染色體不能正常完全隨機(jī)分布的病狀提供了線索，而且具有更廣泛的提示意義——至少10％的基因具有與在X染色體間進(jìn)行“選擇”的機(jī)制相似機(jī)制,。
Nicodemi依靠熱力學(xué)攻克了這道難題,。之前研究已經(jīng)證實(shí)在X染色體失活的關(guān)鍵時(shí)刻，兩條染色體緊密接觸,。Nicodemi等發(fā)現(xiàn)X染色體緊密接觸不久,，蛋白栓的組成物質(zhì)開(kāi)始聚集在兩條X染色體的自殺基因周圍，兩團(tuán)蛋白之間的競(jìng)爭(zhēng)開(kāi)始了,。結(jié)果正如所料,，其中一個(gè)初具模型的蛋白栓勉強(qiáng)獲勝并達(dá)到一個(gè)能級(jí)——能夠?qū)⑿纬蓛蓚€(gè)栓的所有物質(zhì)聚集為一個(gè)蛋白栓。最終的蛋白栓關(guān)閉了其所在X染色體上的XIST自殺基因,，維持了這條染色體的活性,，另一個(gè)XIST自殺基因使其所在X染色體失活。
此觀點(diǎn)被提出后,，哈佛大學(xué)研究人員觀測(cè)到蛋白栓關(guān)閉X染色體XIST基因的過(guò)程,，進(jìn)一步證實(shí)了Nicodemi的研究。Nicodemi博士相信隨機(jī)性有進(jìn)化優(yōu)勢(shì),，意味著基因池中母本染色體和父本染色體數(shù)量相同,，后代的適應(yīng)能力更強(qiáng)。
原始出處：
Symmetry-Breaking Model for X-Chromosome Inactivation
Mario Nicodemi1 and Antonella Prisco2
1Dipartimento di Scienze Fisiche, Università di Napoli “Federico II,” INFN, Via Cintia, 80126 Napoli, Italy
2CNR Institute of Genetics and Biophysics "Buzzati Traverso," Via Pietro Castellino 111, 80131 Napoli, Italy
(Received 14 June 2006; published 7 March 2007)
In mammals, dosage compensation of X linked genes in female cells is achieved by inactivation of one of their two X chromosomes which is randomly chosen. The earliest steps in X-chromosome inactivation (XCI), namely, the mechanism whereby cells count their X chromosomes and choose between two equivalent X chromosomes, remain mysterious. Starting from the recent discovery of X chromosome colocalization at the onset of X-chromosome inactivation, we propose a statistical mechanics model of XCI, which is investigated by computer simulations and checked against experimental data. Our model describes how a “blocking factor” complex is self-assembled and why only one is formed out of many diffusible molecules, resulting in a spontaneous symmetry breaking in the binding to two identical chromosomes. These results are used to derive a scenario of biological implications.
©2007 The American Physical Society
Symmetry breaking Model in X Chromosome Inactivation
Physical Review Letters, vol.98 page 108104
