Data from: Polymorphism in the neurofibromin gene, Nf1, is associated with antagonistic selection on wing size and development time in Drosophila melanogaster

In many invertebrates, body size shows genetically based clines, with size increasing in colder climates. Large body size is typically associated with prolonged development times. We consider variation in the CNS-specific gene neurofibromin 1 (Nf1) and its association with body size and development time. We identified two major Nf1 haplotypes in natural populations, Nf1-insertion-A and Nf1-deletion-G. These haplotypes are characterized by a 45-base insertion/deletion (INDEL) in Nf1 intron 2 and an A/G synonymous substitution (locus L17277). Linkage disequilibrium (LD) between the INDEL and adjacent sites is high but appears to be restricted within the Nf1 gene interval. In Australia, the frequency of the Nf1-insertion-A haplotype increases with latitude where wing size is larger, independent of the chromosomal inversion In(3R)Payne. Unexpectedly, the Nf1-insertion-A haplotype is negatively associated with wing size. We found that the Nf1-insertion-A haplotype is enriched in females with shorter development time. This suggests that the Nf1 haplotype cline may be driven by selection for development time rather than size; females from southern (higher latitude) D. melanogaster populations maintain a rapid development time despite being relatively larger, and the higher incidence of Nf1-insertion-A in southern Australia may contribute to this pattern whereas the effects of the Nf1 haplotypes on size may be countered by other loci with antagonistic effects on size and development time. Our results point to the potential complexity involved in identifying selection on genetic variants exhibiting pleiotropic effects when studies are based on spatial patterns or association studies.在诸多无脊椎动物（invertebrate）中，体型呈现出受遗传调控的渐变群特征：寒冷气候下的个体体型更大。通常而言，体型偏大与更长的发育时长相关联。本研究聚焦于中枢神经系统（Central Nervous System, CNS）特异性基因神经纤维蛋白1（neurofibromin 1, Nf1）的变异，及其与体型和发育时长的关联。我们在自然种群中鉴定出两种主要的Nf1单倍型（haplotype）：Nf1-insertion-A与Nf1-deletion-G。这两种单倍型的特征为：Nf1基因第2内含子区域存在一段45碱基的插入/缺失变异（insertion/deletion, INDEL），以及一处A/G同义替换（synonymous substitution）位点（locus L17277）。插入/缺失变异与邻近位点间的连锁不平衡（Linkage disequilibrium, LD）程度较高，但这种不平衡似乎仅局限于Nf1基因区间内。在澳大利亚，Nf1-insertion-A单倍型的频率随纬度升高而增加，而高纬度区域的翅型更大，且该关联不受染色体倒位In(3R)Payne的影响。但出乎意料的是，Nf1-insertion-A单倍型与翅型大小呈负相关。我们发现，Nf1-insertion-A单倍型在发育时长更短的雌性个体中富集。这表明，Nf1单倍型的渐变群可能由针对发育时长的选择所驱动，而非体型选择：来自南半球（高纬度）黑腹果蝇（Drosophila melanogaster, D. melanogaster）种群的雌性个体，即便体型相对偏大，仍能保持较快的发育速率；而澳大利亚南部地区Nf1-insertion-A单倍型的更高频率或许是这一现象的成因之一。与此同时，Nf1单倍型对体型的影响可能被其他对体型和发育时长存在拮抗效应的基因位点所抵消。本研究结果表明，当研究基于空间分布模式或关联分析时，鉴定携带多效性效应（pleiotropic effect）的遗传变异所受的选择压力，可能存在相当的复杂性。