生物谷報道：Warwick大學研究人員最近揭開了女性細胞在其兩條染色體之間隨機選擇的奧秘,。
男性細胞有X染色體和Y染色體,，女性細胞有兩條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,。這個過程非常關(guān)鍵，出錯會導致嚴重的遺傳疾病,。細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,。研究人員詳細這種自殺基因是通過在其染色體位點上形成一個“蛋白栓”實現(xiàn)自我封閉的,，但不清楚這種過程在兩條染色體間隨機進行的機制。其實研究人員對這種隨機說法非常不滿意,，一直沒有中斷過尋找X染色體隨機失活的規(guī)律,。
最近，Warwick大學物理學家Mario Nicodemi率領(lǐng)的研究小組探清了這種隨機性發(fā)生的機制及其優(yōu)勢,，不僅為研究少數(shù)婦女X染色體不能正常完全隨機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染色體間進行“選擇”的機制相似機制。
Nicodemi依靠熱力學攻克了這道難題,。之前研究已經(jīng)證實在X染色體失活的關(guān)鍵時刻,，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)開始聚集在兩條X染色體的自殺基因周圍,，兩團蛋白之間的競爭開始了。結(jié)果正如所料，其中一個初具模型的蛋白栓勉強獲勝并達到一個能級——能夠?qū)⑿纬蓛蓚€栓的所有物質(zhì)聚集為一個蛋白栓,。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XIST自殺基因使其所在X染色體失活,。
此觀點被提出后，哈佛大學研究人員觀測到蛋白栓關(guān)閉X染色體XIST基因的過程，進一步證實了Nicodemi的研究,。Nicodemi博士相信隨機性有進化優(yōu)勢,，意味著基因池中母本染色體和父本染色體數(shù)量相同，后代的適應能力更強,。
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
