Anholt R R, Fanara J J, Fedorowicz G M, Ganguly I, Kulkarni N H, Mackay T F, Rollmann S M
Department of Zoology, WM Keck Center for Behavioral Biology, North Carolina State University, Raleigh 27695-7617, USA.
Chem Senses. 2001 Feb;26(2):215-21. doi: 10.1093/chemse/26.2.215.
The avoidance response to repellent odorants in Drosophila melanogaster, a response essential for survival, provides an advantageous model for studies on the genetic architecture of olfactory behavior. Transposon tagging in a highly inbred strain of flies in combination with a rapid and simple statistical behavioral assay enables the identification of not only large phenotypic effects, but also small aberrations from wild-type avoidance behavior. The recent completion of the sequence of the Drosophila genome facilitates the molecular characterization of transposon-tagged genes and correlation between gene expression and behavior in smell-impaired (smi) mutant lines. Quantitative genetic analyses of a collection of smi lines in a co-isogenic background revealed an extensive network of epistatic interactions among genes that shape the olfactory avoidance response. Candidate genes for several of these transposon-tagged smi loci implicate genes that mediate odorant recognition, including a novel odorant binding protein; signal propagation, including a voltage-gated sodium channel; and a protein containing multiple leucine rich repeats and PDZ domains likely to be involved in postsynaptic organization in the olfactory pathway. Several novel genes of unknown function have also been implicated, including a novel tyrosine-regulated protein kinase. The discovery and characterization of novel gene products that have major, hitherto unappreciated effects on olfactory behavior will provide new insights in the generation and regulation of odor-guided behavior. The identification and functional characterization of proteins encoded by smi genes that form part of the olfactory subgenome and correlation of polymorphisms in these genes with variation in odor-guided behavior in natural populations will advance our understanding of the genetic architecture of chemosensory behavior.
黑腹果蝇对驱避性气味剂的回避反应是其生存所必需的反应，为嗅觉行为的遗传结构研究提供了一个有利的模型。在高度近交的果蝇品系中进行转座子标签技术，并结合快速简单的统计行为分析，不仅能够识别出大的表型效应，还能识别出与野生型回避行为的小偏差。果蝇基因组序列的最近完成有助于对转座子标签基因进行分子表征，并有助于研究嗅觉受损（smi）突变系中基因表达与行为之间的相关性。对同基因背景下的一组smi品系进行数量遗传学分析，揭示了塑造嗅觉回避反应的基因之间广泛的上位相互作用网络。这些转座子标签的smi位点中的几个候选基因涉及介导气味剂识别的基因，包括一种新型气味结合蛋白；信号传播，包括一种电压门控钠通道；以及一种含有多个富含亮氨酸重复序列和PDZ结构域的蛋白质，可能参与嗅觉通路中的突触后组织。还涉及几个功能未知的新基因，包括一种新型酪氨酸调节蛋白激酶。对嗅觉行为有重大的、迄今未被认识到的影响的新基因产物的发现和表征，将为气味引导行为的产生和调节提供新的见解。对构成嗅觉亚基因组一部分的smi基因编码的蛋白质进行鉴定和功能表征，以及这些基因中的多态性与自然种群中气味引导行为变异的相关性，将推动我们对化学感应行为遗传结构的理解。
