中科院上海生命科學(xué)研究院上海交通大學(xué)醫(yī)學(xué)院健康科學(xué)研究所分子遺傳實驗室殷善葉博士等，在孔祥銀研究員的指導(dǎo)下,，與巴斯大學(xué)教授Hurst合作,，通過整合大規(guī)模芯片數(shù)據(jù)和生物信息學(xué)分析，發(fā)現(xiàn)X染色體基因表達噪音并不比常染色體高,；而常染色單拷貝表達的基因的確具有較高的噪音,。逃脫失活并不會為這些X染色體基因帶來更高的表達豐度或表達噪音。 他們進一步發(fā)現(xiàn)基因表達豐度是決定表達噪音的重要因素,；升高表達水平能降低基因的表達噪音,。
X染色體通過劑量補償機制,，達到和常染色體相似的基因表達豐度,。該工作首次發(fā)現(xiàn)了X染色體不僅基因表達劑量存在補償,，其表達噪音也得到了 “補償”,；并提出單拷貝的X染色體基因表達劑量補償在一定程度上是為了降低其有害的基因表達噪音,。這一研究結(jié)果在線發(fā)表在2009年的Genome Biology雜志上,。
該項工作得到了科技部,、國家自然科學(xué)基金委和中科院項目的支持,。（生物谷Bioon.com）
生物谷推薦原始出處：
Genome Biology 2009, 10:R74doi:10.1186/gb-2009-10-7-r74
Dosage compensation on the active X chromosome minimizes transcriptional noise of X-linked genes in mammals
Shanye Yin , Ping Wang , Wenjun Deng , Hancheng Zheng , Landian Hu , Laurence D Hurst and Xiangyin Kong
Background
Theory predicts that haploid-expressed genes should have noisier expression than comparable diploid-expressed ones with the same expression level. However, in mammals there are several classes of gene that are monoallelically-expressed, including X-linked genes, imprinted genes and some other autosomal genes. Does it follow that the evolution of X chromosomes in eukaryotes comes at the cost of increased transcriptional noise in the heterogametic sex? Moreover, is X-inactivation in mammalian females associated with an increase in transcriptional variation? To address these questions, we analyze gene expression variation between replicate samples of diverse mammalian cell lines in steady-state using microarray data.
Results
We observe that transcriptional variation of X-linked genes is no different to that of autosomal genes both before and after control for transcript abundance. By contrast, autosomal genes subject to allelic exclusion do have unusually high noise levels even allowing for their low transcript abundance. The prior theory we suggest was insufficient, at least as regards X-chromosomes, as it failed to appreciate the regulatory complexity of gene expression, not least the effects of genomic neighbourhood.
Conclusions
These results suggest that high noise is not a necessary consequence of haploid expression and emphasize the primacy of expression level as a determinant of noise. The latter has consequences for understanding the etiology of haplo-insufficiency and the evolution of gene expression levels. Given the coupling between expression level and noise on the X-chromosome, we suggest that part of the selective advantage of dosage compensation is noise abatement of X-linked genes.
