Tandem Duplications and the Limits of Natural Selection in Drosophila yakuba and Drosophila simulans

Abstract

Tandem duplications are an essential source of genetic novelty, and their variation in natural populations is expected to influence adaptive walks. Here, we describe evolutionary impacts of recently-derived, segregating tandem duplications in Drosophila yakuba and Drosophila simulans. We observe an excess of duplicated genes involved in defense against pathogens, insecticide resistance, chorion development, cuticular peptides, and lipases or endopeptidases associated with the accessory glands across both species. The observed agreement is greater than expectations on chance alone, suggesting large amounts of convergence across functional categories. We document evidence of widespread selection on the D. simulans X, suggesting adaptation through duplication is common on the X. Despite the evidence for positive selection, duplicates display an excess of low frequency variants consistent with largely detrimental impacts, limiting the variation that can effectively facilitate adaptation. Standing variation for tandem duplications spans less than 25% of the genome in D. yakuba and D. simulans, indicating that evolution will be strictly limited by mutation, even in organisms with large population sizes. Effective whole gene duplication rates are low at 1.17 × 10-9 per gene per generation in D. yakuba and 6.03 × 10-10 per gene per generation in D. simulans, suggesting long wait times for new mutations on the order of thousands of years for the establishment of sweeps. Hence, in cases where adaptation depends on individual tandem duplications, evolution will be severely limited by mutation. We observe low levels of parallel recruitment of the same duplicated gene in different species, suggesting that the span of standing variation will define evolutionary outcomes in spite of convergence across gene ontologies consistent with rapidly evolving phenotypes.

Fig 1. SFS for tandem duplications in D. yakuba and D. simulans, corrected for ascertainment bias.

A. Site frequency spectra on the autosomes (black) and on the X (grey) in D. yakuba. B. SFS on the autosomes (black) and on the X (grey) in D. simulans. C. SFS for X-linked intronic SNPs (black) and duplicates (white) in D. simulans. The excess of high frequency variants on the X in D. simulans suggests widespread selection for tandem duplicates on the D. simulans X.

Fig 2. Diversity (θ _π) as a function of distance from new mutations in D. yakuba for putatively neutral intronic SNPs (black) and for tandem duplications (red) by chromosome with lowess smoothing.

Duplicates show a reduction in diversity approaching duplications on chromosome 3L, whereas neutral SNPs show no reduction in diversity. Plots exclude centromeric regions and the 4th chromosome which have atypical nucleotide diversity. D. yakuba chromosome 2 displays an atypical pattern of increased diversity and was handled separately from chromosome 3 due to segregating inversions in populations.

Fig 3. Nucleotide diversity, θ _π as a function of distance from new mutations in D. simulans for putatively neutral intronic SNPs (black) and for tandem duplications (red) by chromosome with lowess smoothing.

Duplicates show a reduction in mean diversity approaching duplications on the D. simulans autosomes and X chromosome, whereas neutral SNPs show no reduction in diversity. Plots exclude centromeric regions and the 4th chromosome which have atypical nucleotide diversity. Chromosome 3L is strongly affected by a cluster of duplications at roughly 8.5Mb, which is excluded from the plot, but the effect is still significant without this region.

Fig 4

Histogram of nucleotide diversity, θ _π, (A) For Intergenic mutations (yellow) and duplications that capture gene sequences but do not create chimeric constructs (blue) in D. yakuba. (B) For Intergenic mutations (yellow) and duplications that create chimeric genes (red) in D. yakuba. (C) For Intergenic mutations (yellow) and duplications that capture gene sequences but do not create chimeric constructs (blue) in D. simulans. (D) For Intergenic mutations (yellow) and duplications that create chimeric genes (red) in D. simulans.

Fig 5. Genomewide population mutation rates for all duplications (θ), population sizes (N _e), and per gene mutation rates (μ) for gene structures produced by whole gene duplication, recruitment of non-coding sequence, and chimeric genes by species.

Low mutation rates and mutation limited evolution leads to low levels of parallel recruitment of tandem duplications.

Fig 6

A) Gene ontology classes overrepresented by species among singly duplicated genes or among multiply duplicated genes. B) Number of genes duplicated by species. Most variants are species specific, with small numbers of parallel duplication of orthologs across species.