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.在许多无脊椎动物中，体型呈现出基于遗传的渐变规律：寒冷气候下个体体型更大。较大体型通常与更长的发育时长相关联。本研究聚焦于中枢神经系统特异性（central nervous system-specific, CNS-specific）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：Nf1-插入型-A（Nf1-insertion-A）与Nf1-缺失型-G（Nf1-deletion-G）。这两种单倍型以Nf1内含子2区域的45碱基插入/缺失（insertion/deletion, INDEL）以及位点L17277处的A/G同义替换为特征。插入/缺失位点与邻近位点间的连锁不平衡（linkage disequilibrium, LD）水平较高，但该连锁不平衡仅局限于Nf1基因的基因组区间内。在澳大利亚，Nf1-插入型-A单倍型的频率随纬度升高而增加，此时翅型更大，且该关联不受染色体倒位In(3R)Payne的影响。出乎意料的是，Nf1-插入型-A单倍型与翅型大小呈负相关。我们发现，Nf1-插入型-A单倍型在发育时长更短的雌性个体中富集。这表明Nf1单倍型的渐变规律可能由发育时长的选择压力所驱动，而非体型选择。来自澳大利亚南部（高纬度地区）的黑腹果蝇（Drosophila melanogaster, D. melanogaster）雌性个体，尽管体型相对更大，仍维持了较快的发育速度，而澳大利亚南部种群中Nf1-插入型-A单倍型的高发生率或许促成了这一模式；此外，Nf1单倍型对体型的影响可能被其他对体型与发育时长存在拮抗效应的基因座所抵消。本研究结果表明，当研究基于空间格局或关联分析时，鉴定对具有多效性效应的遗传变异施加的选择压力，其背后涉及的潜在复杂性。