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

Abstract

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.

A clinal polymorphism in the insulin signaling transcription factorfoxocontributes to life‐history adaptation inDrosophila*

“…These examples illustrate the complexity of dissecting clinal selection and the genotype–phenotype map underlying clinal adaptation (Lee et al. ; Paaby et al. ; Flatt ).…”

“…As noted by Lee et al. () and Paaby et al. (), clinal variants subject to countergradient effects might interact epistatically with other loci affecting the trait, or they might be affected by antagonistic selection pressures (Schluter et al.…”

“…Likewise, for a clinal variant of neurofibromin 1 ( Nf1 ), the HL haplotype has smaller wing size, an effect that runs counter to the cline (Lee et al. ). However, as mentioned in the methods, we can of course not completely rule out potentially confounding LD effects that might account for this unexpected result with regard to starvation resistance.…”

Life history evolution and cellular mechanisms associated with increased size in high‐altitude Drosophila

“…In Australian D. melanogaster , haplotypes of the Neurofibromin gene were correlated with antagonistic effects on development time and wing size (Lee et al. 2013). …”

A framework for incorporating evolutionary genomics into biodiversity conservation and management

“…Whilst SNPs are informative and relatively easy to identify, studies on model species have shown that insertion-deletion polymorphisms (indels) also play an important role in genome evolution and adaptation [73][74][75][76]. Identifying indels from high-throughput sequencing data remains a difficult bioinformatic problem [77], and identifying large indels in RRS data is especially difficult because only a small percentage of the genome is sequenced.…”