Tower John
Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089-1340, USA.
Annu Rev Genet. 2004;38:273-304. doi: 10.1146/annurev.genet.37.110801.143851.
Developmentally regulated gene amplification serves to increase the number of templates for transcription, yielding greatly increased protein and/or RNA product for gene(s) at the amplified loci. It is observed with genes that are very actively transcribed and during narrow windows of developmental time where copious amounts of those particular gene products are required. Amplification results from repeated firing of origins at a few genomic loci, while the rest of the genome either does not replicate, or replicates to a lesser extent. As such, amplification is a striking exception to the once-and-only-once rule of DNA replication and may be informative as to that mechanism. Drosophila amplifies eggshell (chorion) genes in the follicle cells of the ovary to allow for rapid eggshell synthesis. Sciara amplifies multiple genes in larval salivary gland cells that encode proteins secreted in the saliva for the pupal case. Finally, Tetrahymena amplifies its rRNA genes several thousand-fold in the creation of the transcriptionally active macronucleus. Due to the ease of molecular and genetic analysis with these systems, the study of origin regulation has advanced rapidly. Comparisons reveal an evolutionarily conserved trans-regulatory apparatus and a similar organization of sequence-specific cis-regulatory replicator and origin elements. The studies indicate a regulatory role for chromatin structure and transcriptionally active genes near the origins.
发育调控的基因扩增用于增加转录模板的数量，从而使扩增位点处的基因产生大量增加的蛋白质和/或RNA产物。在非常活跃转录的基因以及在发育时间的狭窄窗口期间，当需要大量特定基因产物时，会观察到这种情况。扩增是由于少数基因组位点的起始点反复激活，而基因组的其余部分要么不复制，要么复制程度较低。因此，扩增是DNA复制一次且仅复制一次规则的一个显著例外，并且可能为该机制提供信息。果蝇在卵巢的卵泡细胞中扩增卵壳（绒毛膜）基因，以便快速合成卵壳。蕈蚊在幼虫唾液腺细胞中扩增多个基因，这些基因编码分泌到唾液中用于蛹壳的蛋白质。最后，四膜虫在形成转录活跃的大核时将其rRNA基因扩增数千倍。由于这些系统易于进行分子和遗传分析，起源调控的研究进展迅速。比较结果揭示了一种进化上保守的反式调控装置以及序列特异性顺式调控复制子和起始元件的相似组织。这些研究表明染色质结构和起始点附近转录活跃基因具有调控作用。
