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Comparative Study
. 2006 May;173(1):197-205.
doi: 10.1534/genetics.105.054098. Epub 2006 Feb 19.

High-resolution Quantitative Trait Locus Mapping Reveals Sign Epistasis Controlling Ovariole Number Between Two Drosophila Species

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Free PMC article
Comparative Study

High-resolution Quantitative Trait Locus Mapping Reveals Sign Epistasis Controlling Ovariole Number Between Two Drosophila Species

Virginie Orgogozo et al. Genetics. .
Free PMC article

Abstract

Identifying the genes underlying genetically complex traits is of fundamental importance for medicine, agriculture, and evolutionary biology. However, the level of resolution offered by traditional quantitative trait locus (QTL) mapping is usually coarse. We analyze here a trait closely related to fitness, ovariole number. Our initial interspecific mapping between Drosophila sechellia (8 ovarioles/ovary) and D. simulans (15 ovarioles/ovary) identified a major QTL on chromosome 3 and a minor QTL on chromosome 2. To refine the position of the major QTL, we selected 1038 additional recombinants in the region of interest using flanking morphological markers (selective phenotyping). This effort generated approximately one recombination event per gene and increased the mapping resolution by approximately seven times. Our study thus shows that using visible markers to select for recombinants can efficiently increase the resolution of QTL mapping. We resolved the major QTL into two epistatic QTL, QTL3a and QTL3b. QTL3a shows sign epistasis: it has opposite effects in two different genetic backgrounds, the presence vs. the absence of the QTL3b D. sechellia allele. This property of QTL3a allows us to reconstruct the probable order of fixation of the QTL alleles during evolution.

Figures

Figure 1.
Figure 1.
Variation in ovariole number in the D. melanogaster subgroup. (A) Phylogeny (Powell 1997; Harr et al. 1998; Ting et al. 2000) showing the range in number of ovarioles per ovary for each species (David and Bocquet 1975b; Louis and David 1986; Coyne et al. 1991; Hodin and Riddiford 2000). (B) Ovarian morphology in D. melanogaster, D. simulans, and D. sechellia. Bar, 200 μm. (C) Mean ovariole number and standard deviation for D. melanogaster (Oregon-R, n = 44 flies), D. simulans f;nt,pm;st,e (n = 29), D. sechellia (n = 48), F1 hybrids D. sechellia/D. simulans (n = 47), progeny from the D. sechellia (n = 226) and D. simulans backcrosses (n = 383).
Figure 2.
Figure 2.
Composite interval mapping of mean ovariole number between D. sechellia and D. simulans for the D. sechellia backcross (A) and the D. simulans backcross (B). Marker positions are indicated along the x-axis and LOD score on the y-axis. The asterisks indicate the positions of the background parameters (see supplemental material at http://www.genetics.org/supplemental/). The estimated effect of QTL is shown at the top of each peak and is expressed in ovariole number. The LOD threshold for a 5% significance threshold, estimated by a permutation test, is represented as a dotted line.
Figure 3.
Figure 3.
High-resolution QTL mapping of the D. simulans backcross. (A) Section of chromosome 3. (B) Entire chromosome 2. Representation is as in Figure 2. Cytological locations of markers are shown along the x-axis. The shaded bar indicates the position of the inversion breakpoint relative to D. melanogaster. Results from composite interval mapping for the first backcross (light shaded line), the second backcross (dark shaded line), and the total analysis of both first and second backcrosses (solid line) are presented.
Figure 4.
Figure 4.
Two-dimensional scan for linked QTL on chromosome 3. Values are given as a function of the two QTL positions tested by the model. Cytological locations are indicated for each marker. (A) The LOD score (relative to a model with no QTL) for the three-QTL model with a QTL in fixed position on chromosome 2 and two interacting QTL in varying positions on chromosome 3. (B) The interaction LOD score, comparing the model with two interacting QTL on chromosome 3 to that with additive QTL on chromosome 3. (C) The estimated effect of substituting one D. simulans allele by a D. sechellia allele at QTL3a (in a D. simulans background at QTL3a and QTL3b positions). (D) The estimated effect of substituting a D. simulans allele by a D. sechellia allele at QTL3b (in a D. simulans background at QTL3a and QTL3b positions). (E) The estimated effect of substituting a D. simulans allele by a D. sechellia allele at both QTL3a and QTL3b (in a D. simulans background for QTL3a and QTL3b). In A–E, the location of the QTL on chromosome 2 is kept fixed. The estimated locations of the two QTL are indicated by a cross and the 2-LOD support region by a thick solid line. Iso-LOD lines are shown in A with thin solid lines.
Figure 5.
Figure 5.
Two evolutionary scenarios for the evolution of ovariole number. Only QTL3a and QTL3b are considered here. We assume that the ancestor of D. simulans and D. sechellia was D. simulans-like, with genotype QTL3a sim/sim, QTL3b sim/sim, and an initial phenotype of 15 ovarioles. In A, the QTL3a mutation appears first and is followed by the QTL3b mutation. B represents the alternative scenario. The estimated number of ovarioles and standard error are indicated at each evolutionary step (based on Table 1). Although it is possible that one QTL was fixed before the origin of the second, the se/se allelic conditions are not shown because we do not have ovariole number estimates for the se/se genotypes. If we assume that mutations that increase ovariole number (open inverted triangle) decreased fitness during D. sechellia evolution, then A is unlikely and B, which involves successive mutations that decrease ovariole number (shaded triangle), is more likely. sim, simulans; se, sechellia.

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