颜林林 (2022-08-30 23:47):
#paper doi:10.1016/j.gpb.2022.08.003 Genomics, Proteomics & Bioinformatics, 2022, Dynamic Spatial-temporal Expression Ratio of X Chromosome to Autosomes but Stable Dosage Compensation in Mammals. 哺乳动物的性染色体,在雌性和雄性中分别为XX和XY,也即X染色体的数量在雌雄之间相差了一倍,然而X染色体上的基因并未因此在两性之间出现巨大的表达差异,这个现象称为剂量补偿效应。本文通过收集和分析多组学数据,包括转录组(RNA-seq)、翻译组(Ribo-seq)、蛋白组(质谱),涉及不同物种(人、鸭嘴兽、负鼠;使用鸡作为外类群),以及(小鼠模型的)不同发育阶段,对此现象进行了深入细致的研究。采用将X染色体连锁的各基因表达,与常染色体基因表达、直系同源基因的表达,分别计算比值,评估剂量补偿效应的量化情况,发现该表达量比值,在不同组织和不同发育阶段,存在时空动态性,且与演化相关。很有意思的一篇生信文章。
Dynamic Spatial-temporal Expression Ratio of X Chromosome to Autosomes but Stable Dosage Compensation in Mammals
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Abstract:
In the evolutionary model of dosage compensation, per-allele expression level of the X chromosome has been proposed to have twofold up-regulation to compensate its dose reduction in males (XY) compared to females (XX). However, the expression regulation of X-linked genes is still controversial, and comprehensive evaluations are still lacking. By integrating multi-omics datasets in mammals, we investigated the expression ratios including X to autosomes (X:AA ratio) and X to orthologs (X:XX ratio) at the transcriptome, translatome, and proteome levels. We revealed a dynamic spatial-temporal X:AA ratio during development in humans and mice. Meanwhile, by tracing the evolution of orthologous gene expression in chickens, platypuses, and opossums, we found a stable expression ratio of X-linked genes in humans to their autosomal orthologs in other species (X:XX ≈ 1) across tissues and developmental stages, demonstrating stable dosage compensation in mammals. We also found that different epigenetic regulations contributed to the high tissue specificity and stage specificity of X-linked gene expression, thus affecting X:AA ratios. It could be concluded that the dynamics of X:AA ratios were attributed to the different gene contents and expression preferences of the X chromosome, rather than the stable dosage compensation.
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