Rogers A S, Escher Stefan A, Pasetto C, Rosato E, Costa R, Kyriacou C P
Department of Genetics, University of Leicester, Leicester LE1 7RH, UK.
Genetica. 2004 Mar;120(1-3):223-32. doi: 10.1023/b:gene.0000017643.62084.96.
The length of the Thr-Gly repeat within the period gene of Drosophilids, coevolves with its immediate flanking region to maintain the temperature compensation of the fly circadian clock. In Drosophila simulans, balancing selection appears to maintain a polymorphism in this region, with three repeat lengths carrying 23, 24 or 25 Thr-Gly pairs, each in complete linkage disequilibrium with a distinctive flanking region amino acid moiety. We wondered whether separating a specific length repeat from its associated flanking haplotype might have functional implications for the circadian clock. We fortuitously discovered a population of flies collected in Kenya, in which a chimeric Thr-Gly haplotype was segregating that carried the (Thr-Gly)24 repeat, but the flanking region of a (Thr-Gly)23 allele. One of the five isofemale lines that carried this 'mutant' Thr-Gly sequence showed a dramatically long and temperature-sensitive free-running circadian period. This phenotype was mapped to the X chromosome, close to the D. simulans per gene, but there was also a significant effect of a modifying autosomal locus or loci. It seems remarkable that such a mutant phenotype should be discovered in a screen of chimeric Thr-Gly regions.
果蝇period基因内苏氨酸 - 甘氨酸重复序列的长度与其紧邻的侧翼区域共同进化，以维持果蝇生物钟的温度补偿。在拟暗果蝇中，平衡选择似乎维持了该区域的多态性，有三种重复长度分别携带23、24或25个苏氨酸 - 甘氨酸对，每一种都与一个独特的侧翼区域氨基酸部分完全连锁不平衡。我们想知道，将特定长度的重复序列与其相关的侧翼单倍型分离，是否会对生物钟产生功能影响。我们偶然发现了一群在肯尼亚采集的果蝇，其中一种嵌合的苏氨酸 - 甘氨酸单倍型正在分离，它携带（苏氨酸 - 甘氨酸）24重复序列，但侧翼区域是（苏氨酸 - 甘氨酸）23等位基因的。携带这种“突变”苏氨酸 - 甘氨酸序列的五个同雌系之一，表现出显著延长且对温度敏感的自由运转生物钟周期。这种表型被定位到X染色体上，靠近拟暗果蝇的per基因，但一个或多个修饰性常染色体位点也有显著影响。在嵌合苏氨酸 - 甘氨酸区域的筛选中发现这样一种突变表型，似乎很不寻常。
