Melamed Esther, Arnold Arthur P
Department of Physiological Science, and Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, CA 90095-1606, USA.
Genome Biol. 2007;8(9):R202. doi: 10.1186/gb-2007-8-9-r202.
Most Z chromosome genes in birds are expressed at a higher level in ZZ males than in ZW females, and thus are relatively ineffectively dosage compensated. Some Z genes are compensated, however, by an unknown mechanism. Previous studies identified a non-coding RNA in the male hypermethylated (MHM) region, associated with sex-specific histone acetylation, which has been proposed to be involved in dosage compensation.
Using microarray mRNA expression analysis, we find that dosage compensated and non-compensated genes occur across the Z chromosome, but a cluster of compensated genes are found in the MHM region of chicken chromosome Zp, whereas Zq is enriched in non-compensated genes. The degree of dosage compensation among Z genes is predicted better by the level of expression of Z genes in males than in females, probably because of better compensation of genes with lower levels of expression. Compensated genes have different functional properties than non-compensated genes, suggesting that dosage compensation has evolved gene-by-gene according to selective pressures on each gene. The group of genes comprising the MHM region also resides on a primitive mammalian (platypus) sex chromosome and, thus, may represent an ancestral precursor to avian ZZ/ZW and monotreme XX/XY sex chromosome systems.
The aggregation of dosage compensated genes near the MHM locus may reflect a local sex- and chromosome-specific mechanism of dosage compensation, perhaps mediated by the MHM non-coding RNA.
鸟类中大多数Z染色体基因在ZZ雄性中的表达水平高于ZW雌性，因此剂量补偿相对无效。然而，一些Z基因通过未知机制实现了补偿。先前的研究在雄性高甲基化（MHM）区域鉴定出一种非编码RNA，其与性别特异性组蛋白乙酰化相关，有人提出该RNA参与剂量补偿。
通过微阵列mRNA表达分析，我们发现剂量补偿基因和非补偿基因分布于整个Z染色体，但在鸡Z染色体Zp的MHM区域发现了一组补偿基因，而Zq富含非补偿基因。Z基因间的剂量补偿程度在雄性中比在雌性中能更好地通过Z基因的表达水平来预测，这可能是因为表达水平较低的基因能得到更好的补偿。补偿基因与非补偿基因具有不同的功能特性，这表明剂量补偿是根据每个基因所承受的选择压力逐基因进化而来的。包含MHM区域的基因群也存在于原始哺乳动物（鸭嘴兽）的性染色体上，因此可能代表了鸟类ZZ/ZW和单孔目动物XX/XY性染色体系统的祖先前体。
剂量补偿基因在MHM位点附近的聚集可能反映了一种局部的、性别和染色体特异性的剂量补偿机制，或许是由MHM非编码RNA介导的。
