Qtl Input Pipeline.

Genetic variants underlying traits that become either non-adaptive or selectively neutral are expected to have altered evolutionary trajectories. Uncovering genetic signatures associated with phenotypic loss presents the opportunity to discover the molecular basis for the phenotype in populations where it persists. Here we study circalunar clocks in populations of the marine midge Clunio marinus. The circalunar clock synchronizes development to the lunar phase, and it is set by moonlight and tidal cycles of mechanical agitation. Two out of ten studied populations have lost their sensitivity to mechanical agitation while preserving sensitivity to moonlight. Intriguingly, the F1 offspring of the two insensitive populations regained the sensitivity to mechanical entrainment, implying a genetically independent loss of the phenotype. By combining quantitative trait locus mapping and genome-wide screens, we explored the genetics of this phenotypic loss. QTL analysis suggested an oligogenic origin with one prevalent additive locus in one of the strains. In addition, it confirmed a distinct genetic architecture in the two insensitive populations. Genomic screens further uncovered several candidate genes underlying QTL regions. The strongest signal under the most prominent QTL contains a duplicated STAT1 gene, which has a well-established role in development, and CG022363, an ortholog of the Drosophila melanogaster CG32100 gene, which plays a role in gravitaxis. Our results support the notion that adaptive phenotypes have a complex genetic basis with mutations occurring at several loci. By dissecting the most prevalent signals, we started to reveal the molecular machinery responsible for the entrainment of the circalunar clock.那些导致性状变为非适应性或选择性中性的遗传变异，预计将改变其演化轨迹。揭示与表型丢失相关的遗传特征，可为该表型仍存续的种群中解析该表型的分子基础提供契机。本研究聚焦于海洋摇蚊（Clunio marinus）种群的月周节律钟（circalunar clock）。月周节律钟可将发育进程与月相同步，其授时信号由月光以及机械搅动的潮汐周期所调控。在所研究的10个种群中，有2个种群丧失了对机械搅动刺激的敏感性，但仍保留对月光的响应能力。有趣的是，这两个不敏感种群的F1子代重新恢复了对机械授时的敏感性，这表明该表型的丢失为遗传上独立的事件。本研究结合数量性状位点（quantitative trait locus，QTL）定位与全基因组筛选技术，探究了该表型丢失的遗传机制。QTL分析提示该性状的遗传基础为寡基因调控，其中一个品系存在一个主要的加性位点；此外，分析证实这两个不敏感种群具有独特的遗传架构。全基因组筛选进一步在QTL区域内发现了多个候选基因。位于最显著QTL下的最强信号区域包含一对重复的STAT1基因（其在发育过程中的功能已得到充分阐明），以及黑腹果蝇（Drosophila melanogaster）CG32100基因的同源基因CG022363，该基因参与趋重力性调控。本研究结果支持“适应性表型具有复杂的遗传基础，突变可发生于多个基因座”这一观点。通过解析最关键的信号通路，我们初步揭示了调控月周节律钟授时的分子机制。