Polyglutamine expansion in Drosophila:: thermal stress and Hsp70 as selective agents
Polyglutamine expansion in Drosophila:: thermal stress and Hsp70 as selective agents
复制标题
DOI：
10.1007/s12038-007-0053-9
复制
发表时间：
2007-04-01
影响因子：
2.9
通讯作者：
Nimali, Mario
中科院分区：
文献类型：
--
作者：
Bettencourt, Brian R.;Hogan, Catherine C.;Nimali, Mario
编码多聚谷氨酰胺束的重复 DNA 序列易于扩增并导致高度有害的神经变性表型。尽管有这种趋势，多聚谷氨酰胺束（“polyQs”）仍然是真核基因组的保守特征。 PolyQ 是昆虫基因组中最常见的蛋白质编码同型重复序列，主要存在于编码从果蝇到人类保守的转录因子的基因中。尽管在不同物种之间高度保守，但 polyQ 长度在物种内差异很大。在黑腹果蝇中，25 个基因中的多 Q 比所有其他多氨基酸束具有更多的等位基因和更高的杂合性。热休克蛋白 Hsp70 是 polyQ 扩展的主要抑制因子，可能在调节编码它们的等位基因的表型中发挥关键作用。 Hsp70 还可以促进果蝇和多种生物体对自然热应激的耐受性，这一作用可能会耗尽伴侣蛋白对 PolyQ 毒性的缓冲作用。因此，在压力环境中，针对更容易扩增和有害表型的长polyQ等位基因的自然选择可能更有效。这一假设可以通过测量黑腹果蝇经历自然热应激时 Hsp70 和 polyQ 转基因之间的表型相互作用来检验，这是一种将比较基因组学与实验和生态遗传学相结合的方法。
Repetitive DNA sequences that encode polyglutamine tracts are prone to expansion and cause highly deleterious phenotypes of neurodegeneration. Despite this tendency, polyglutamine tracts ("polyQs") are conserved features of eukaryotic genomes. PolyQs are the most frequent protein-coding homotypic repeat in insect genomes, and are found predominantly in genes encoding transcription factors conserved from Drosophila through human. Although highly conserved across species, polyQ lengths vary widely within species. In D. melanogaster, polyQs in 25 genes have more alleles and higher heterozygosity than all other poly-amino acid tracts. The heat shock protein Hsp70 is a principal suppressor of polyQ expansions and may play a key role in modulating the phenotypes of the alleles that encode them. Hsp70 also promotes tolerance of natural thermal stress in Drosophila and diverse organisms, a role which may deplete the chaperone from buffering against polyQ toxicity. Thus in stressful environments, natural selection against long polyQ alleles more prone to expansion and deleterious phenotypes may be more effective. This hypothesis can be tested by measuring the phenotypic interactions between Hsp70 and polyQ transgenes in D. melanogaster undergoing natural thermal stress, an approach which integrates comparative genomics with experimental and ecological genetics.