1. Evolutionary Biology
  2. Genetics and Genomics

Gene flow mediates the role of sex chromosome meiotic drive during complex speciation

  1. Colin D Meiklejohn  Is a corresponding author
  2. Emily L Landeen
  3. Kathleen E Gordon
  4. Thomas Rzatkiewicz
  5. Sarah B Kingan
  6. Anthony J Geneva
  7. Jeffrey P Vedanayagam
  8. Christina A Muirhead
  9. Daniel Garrigan
  10. David L Stern
  11. Daven C Presgraves  Is a corresponding author
  1. University of Nebraska, United States
  2. University of Rochester, United States
  3. Janelia Research Campus, Howard Hughes Medical Institute, United States
https://doi.org/10.7554/eLife.35468
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Cite this article
  1. Colin D Meiklejohn
  2. Emily L Landeen
  3. Kathleen E Gordon
  4. Thomas Rzatkiewicz
  5. Sarah B Kingan
  6. Anthony J Geneva
  7. Jeffrey P Vedanayagam
  8. Christina A Muirhead
  9. Daniel Garrigan
  10. David L Stern
  11. Daven C Presgraves
(2018)
Gene flow mediates the role of sex chromosome meiotic drive during complex speciation
eLife 7:e35468.
https://doi.org/10.7554/eLife.35468
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7 figures, 7 tables and 4 additional files

Figures

Figure 1 with 1 supplement
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Crosses used to introgress eight regions of the D. mauritiana X chromosome into a D. simulans genome.

(A) D. mauritiana ‘2P’ lines were constructed by combining pairs of P-element insertions containing the miniwhite transgene (P[w+]; red triangles) distributed across the X chromosome. The P[w+] inserts are semi-dominant visible eye-color markers that permit discrimination of individuals carrying 0, 1 or 2P[w+]. X-linked segments from D. mauritiana were introgressed into a D. simulans genetic background by backcrossing 2P[w+] hybrid females to D. simulans wXD1 males for over 40 generations. Each introgression line was then bottlenecked through a single female to eliminate segregating variation in the recombination breakpoints flanking the 2P[w+] interval. (B) Cytological map of the D. melanogaster X chromosome, indicating the locations of P[w+] and pBac[eYFP] transgene insertions. The extent of regions introgressed from D. mauritiana into D. simulans (e.g. 2P-1) are labeled above the map. Two pairs of introgression genotypes (2P-5a/b and 2P-6a/b) mostly overlap; the regions included in 2P-5b/2P-6b but not 2P-5a/2P-6a are indicated by dashed lines. (C) Meiotic mapping of sterility factors. 2P[w+] females were crossed to D. simulans strains carrying an X-linked pBac[eYFP] transgene (yellow triangles) that was used as an additional visible marker to score recombinant chromosomes. Recombinant X chromosomes with both pBac[eYFP] and a single P[w+] were chosen and assayed for male fertility. Recombinant chromosomes were generated using pBac[eYFP] markers both proximal and distal to each 2P introgression.

https://doi.org/10.7554/eLife.35468.002
Figure 1—source data 1

Source data for Figure 1—figure supplement 1, Figure 4—figure supplement 1.

https://doi.org/10.7554/eLife.35468.004
Figure 1—source data 2

Source data for Figure 1—figure supplement 1, Figure 4—figure supplement 1.

https://doi.org/10.7554/eLife.35468.005
Figure 1—source data 3

Source data for Figure 1—figure supplement 1.

https://doi.org/10.7554/eLife.35468.006
Figure 1—figure supplement 1
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Distribution of fertility (number of progeny) among all males carrying recombinant 1P-YFP X chromosomes, and average number of progeny among all 1P-YFP genotypes.

Colored bars and arrow below indicate individual male and mean fertility for D. simulans wXD1, respectively. The mean fertility of 10 replicate D. mauritiana w12 males with D. simulans wXD1 females is 197.2 offspring.

https://doi.org/10.7554/eLife.35468.003
Figure 2 with 1 supplement
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High-resolution genetic map of X-linked hybrid male sterility.

Colored horizontal bars indicate the extent of introgressed D. mauritiana alleles for each recombinant 1P-YFP X chromosome. The color of each introgression indicates the mean fertility of 10 replicate males carrying that 1P-YFP X chromosome. The three shaded areas indicate fertile regions within which D. mauritiana introgressions do not cause sterility, whereas the four red arrows indicate small candidate sterility regions. The blue arrowhead indicates the location of the Dox/MDox meiotic drive loci. Lines in the lower panel indicate the average number of offspring and average proportion of sterile males (defined as producing fewer than five offspring) for all 1P-YFP genotypes that carry D. mauritiana alleles at each genotyped SNP.

https://doi.org/10.7554/eLife.35468.009
Figure 2—source data 1

Source data for Figure 2, Figure 2—figure supplement 1, Figure 4.

https://doi.org/10.7554/eLife.35468.011
Figure 2—figure supplement 1
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SNP locations and inferred ancestry for five recombinant 1P-YFP genotypes.

Red ticks indicate D. simulans alleles (par1), blue ticks indicate D. mauritiana alleles (par2), and the red (blue) shaded regions indicate the location of inferred D. simulans (D. mauritiana) ancestry.

https://doi.org/10.7554/eLife.35468.010
Figure 3 with 2 supplements
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QTL analysis of male fertility.

Mean offspring counts for each genotype were transformed as log10(N + 1). The top plot shows lod scores for a two-part model that treats completely sterile genotypes as one class, and tests for quantitative effects on fertility among non-sterile genotypes. The solid and dotted gray lines indicate 5% and 1% significance thresholds, respectively, determined from 10,000 permutations. The bottom plot shows the estimated effects of D. simulans and D. mauritiana alleles at QTL placed every 1 cM (bounding lines indicate 95% confidence intervals).

https://doi.org/10.7554/eLife.35468.012
Figure 3—source data 1

Source data for Figure 3, Figure 3—figure supplement 1, Figure 3—figure supplement 2, Figure 4—figure supplement 3.

https://doi.org/10.7554/eLife.35468.015
Figure 3—figure supplement 1
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Alternate QTL models of male fertility.

Lod scores are shown for models where offspring counts for each genotype were modeled as a normally distributed variable (normal), log10(N + 1) offspring counts were modeled as a normally distributed variable (normal (log)), or offspring counts were modeled as two classes, completely sterile genotypes as one class, and tests for quantitative effects on fertility among non-sterile genotypes. Horizontal lines indicate 1% significance thresholds determined from 10,000 permutations.

https://doi.org/10.7554/eLife.35468.013
Figure 3—figure supplement 2
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QTL analysis of male fertility incorporating introgression length as a covariate.

Lod scores are shown for analyses where offspring log10(N + 1) offspring counts were treated as a normally distributed variable, without and with introgression length in base-pairs as a covariate. Horizontal lines indicate 1% significance thresholds determined from 10,000 permutations.

https://doi.org/10.7554/eLife.35468.014
Figure 4 with 3 supplements
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High-resolution map of progeny sex ratios among fertile 1P-YFP introgression male genotypes.

Colored horizontal bars indicate the extent of introgressed D. mauritiana alleles for each fertile recombinant 1P-YFP X chromosome. The color of each introgression indicates the sex-ratio of progeny from replicate males carrying that 1P-YFP X chromosome. The line below indicates the average progeny sex-ratio for all 1P-YFP genotypes that carry D. mauritiana alleles at each genotyped SNP.

https://doi.org/10.7554/eLife.35468.017
Figure 4—figure supplement 1
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Relationship between progeny number and sex-ratio.

The top panel shows number of progeny and the percentage of daughters for all recombinant 1P-YFP males that produced any offspring and 40 control D. simulans wXD1 males. The bottom panel shows mean number of progeny and mean progeny sex-ratio for all recombinant 1P-YFP genotypes. In all cases, there is a significant positive correlation between fertility and progeny sex-ratio (1P-YFP males: ρ = 0.12, p<0.0001; wXD1 males: ρ=0.44, p=0.009; 1P-YFP genotypes: ρ = 0.21, p=0.0002).

https://doi.org/10.7554/eLife.35468.018
Figure 4—figure supplement 2
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Relationship between introgression length, fertility, and sex-ratio.

Partial correlation coefficients among these three variables: length, fertility: ρ = 0.03, p=0.67; fertility, sex-ratio: ρ = 0.16, p=0.02; length, sex-ratio: ρ = −0.31, p<0.0001). Trendline corresponds to linear regression of progeny sex-ratio on introgression length: sex-ratio = 0.487 - length*0.022.

https://doi.org/10.7554/eLife.35468.019
Figure 4—figure supplement 3
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QTL analysis of progeny sex ratio associated with introgression genotypes.

Top panel includes all males that produced any offspring; bottom panel includes only males that sired more than four offspring and genotypes with at least three males that sired more than four offspring. Grey lines indicate results using all genotypes that met the above criterion; black lines indicate results excluding a single outlier genotype. Solid and dotted lines indicate 5% and 1% significance thresholds determined from 10,000 random permutations, respectively.

https://doi.org/10.7554/eLife.35468.020
Figure 5 with 2 supplements
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Identification of introgessed regions by Gmin.

Grey (black) dots indicate Gmin values calculated using 5-kb (10-kb) windows; light blue (dark blue) dots indicate 5-kb (10-kb) windows with significant Gmin values. As with 10-kb windows, 5-kb windows with significant Gmin values are 4-fold underrepresented on the X chromosome: 14 of 3603 5-kb windows on the X chromosome (0.39%) have significant Gmin values versus 266 of 17,065 5-kb windows on the autosomes (1.56%; Fisher’s exact test p<0.0001).

https://doi.org/10.7554/eLife.35468.022
Figure 5—source data 1

Source data for Figure 5—figure supplements 1 and 2.

https://doi.org/10.7554/eLife.35468.025
Figure 5—source data 2

Source data for Figure 5.

https://doi.org/10.7554/eLife.35468.026
Figure 5—figure supplement 1
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Population genomic scans for polymorphism, divergence, and introgression in 10-kb windows.

The rows of panels show: nucleotide diversity for a sample of 10 inbred strains of D. mauritiana (πmau, green dots) and 20 inbred strains of D. simulans (πsim, purple dots); nucleotide divergence scaled by within-species polymorphism (blue dots); and Gmin (red dots), the ratio of the minimum number of nucleotide differences per site between D. mauritiana and D. simulans to the average number of differences per site, a summary statistic that is sensitive to introgression. Panels correspond to each major chromosome arm, with genome coordinates on the x-axis.

https://doi.org/10.7554/eLife.35468.023
Figure 5—figure supplement 2
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Polymorphism and Gmin.

Within both D. simulans and D. mauritiana there is a significant negative correlation between polymorphism (π) and Gmin P-value (Spearman's ρ = 0.22 and 0.38, respectively, p<0.0001), indicating that windows with higher polymorphism are more likely to have low Gmin values, although this correlation is driven by the large majority of non-significant windows. However, 10-kb windows with significant Gmin values have lower levels of polymorphism in D. simulans than non-significant windows, while significant windows have higher levels of polymorphism in D. mauritiana than non-significant windows (Wilcoxon rank test p<0.0001 within both species). One interpretation of this pattern is that windows with significant Gmin values have levels of polymorphism similar to that in the other species, which is consistent with these windows carrying lineages derived from the other species.

https://doi.org/10.7554/eLife.35468.024
Figure 6
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Natural introgression of the MDox-Dox region of the X chromosome.

(A) Gmin values for 10-kb windows in the region containing MDox and Dox. Blue lines indicate windows with significantly low Gmin values. Inset box indicates the 90-kb region shown in panel B. (B) DNA polymorphism tables: the top table corresponds to the MDox region, and the bottom corresponds to the Dox region. Within the tables, yellow squares denote the derived nucleotide state, and blue squares indicate the ancestral state. The top 20 rows of each table correspond to the D. simulans samples, and the bottom 10 rows correspond to the D. mauritiana samples. The genome map between the polymorphism tables shows gene models for the region (orange boxes) and the locations of the MDox and Dox genes (green triangles). Regions highlighted in red are 10-kb windows with significantly low Gmin values. (C) Maximum likelihood phylogenetic trees for the MDox and Dox regions. Green circles and red triangles denote D. mauritiana and D. simulans samples, respectively.

https://doi.org/10.7554/eLife.35468.027
Figure 6—source data 1

Source data for Figure 6.

https://doi.org/10.7554/eLife.35468.028
Appendix 1—figure 1
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Resampled autosomal 10-kb windows matching X-chromosome polymorphism.

(A) Distributions of polymorphism within 10-kb windows for the X chromosome and autosomes in D. simulans and D. mauritiana. (B) Exemplar resampled autosomal data sets matching X-chromosome polymorphism for D. simulans and D. mauritiana. (C) Distribution of the number of resampled windows with significant Gmin values across 10,000 replicate resampled data sets. Vertical dotted lines indicate the observed number of significant X-linked windows in each species.

https://doi.org/10.7554/eLife.35468.036

Tables

Table 1
Locations and lengths of 2P intervals.
https://doi.org/10.7554/eLife.35468.007
2P intervalLeft P[w+]*Right P[w+]*Length (Mbp)
2P-199341944985203.51
2P-3619255591261332.93
2P-49126133111898732.06
2P-5a11189873133240172.13
2P-5b11189873139039342.71
2P-6a13903934174920843.59
2P-6b13324017174920844.17
2P-717492084186600371.17

  1. *coordinate position in the assembled D. simulans w501 genome

Table 2
Fertility and sex ratio phenotypes for 1P-YFP recombinant genotypes.
https://doi.org/10.7554/eLife.35468.008
2P intervalN testedN sterile*N sub-fertileN fertile†Mean fertility†% fertile†Mean SR†
2P-1171482010372.20.600.43
2P-39712216467.40.660.45
2P-4771795171.90.660.45
2P-5a/b9223165368.20.580.51
2P-6a/b9769101873.80.190.44
2P-7836968136.50.100.47
all 1P-YFP genotypes6172388229781.70.480.45

  1. *genotypes where no male produced any offspring

    †genotypes where at least two males produced at least five offspring

Table 3
Distribution of 1P-YFP recombinant introgression lengths.
https://doi.org/10.7554/eLife.35468.016
2P intervalSequencedMin sizeMean sizeMax size
2P-1129295,2252,617,8336,322,871
2P-373306,0521,636,9443,818,569
2P-455226,0181,482,6592,917,578
2P-561365,0041,627,6323,276,930
2P-655692,3502,400,4994,764,204
2P-766218,7221,412,1082,502,552
Table 4
Population genomics summary statistics.
https://doi.org/10.7554/eLife.35468.021
InferenceStatistic*D. simulansD. mauritianaP-value
Polymorphismmedian πX0.01190.0076< 0.0001‡
median πA0.01520.0116< 0.0001‡
SNPs with inferred ancestry†4,324,7402,181,959<0.0001§
% ancestral SNPs14.621.6<0.0001#
% derived SNPs85.378.3
Site frequency spectramedian Tajima's DX−1.218−0.536< 0.0001c
median Tajima's DA−1.127−0.359< 0.0001c
Linkage disequilibriummedian Zns, X0.0560.122< 0.0001c
median Zns, A0.0580.129< 0.0001c

  1. *Summary statistics estimated from 10-kb non-overlapping windows.

    †SNP were inferred as ancestral or derived using parsimony, with D. melanogaster as an outgroup (see Materials and methods).

  2. ‡P-value for Mann-Whitney U-test.

    §P-value for χ2-test.

  3. #P-value from Fisher's exact test.

Key resources table
Reagent type
(species) or resource		DesignationSource or referenceIdentifiersAdditional information
Genetic reagent
(Drosophila mauritiana)		mau w[12]Drosophila species
stock center; NCBI SRA		14021–0241.60;
SRX684364;
SRX135546
Genetic reagent
(Drosophila simulans		sim w[XD1]this paperSRR8247551obtained from J. Coyne
Genetic reagent
(Drosophila mauritiana)		2P-1this paperw[12], P{w[+]=Neneh2},
P{w[+]=4R1}
Genetic reagent
(Drosophila mauritiana)		2P-3this paperw[12], P{w[+]=Ophelia1},
P{w[+]=4J1}
Genetic reagent
(Drosophila mauritiana)		2P-4this paperw[12], P{w[+]=4J1},
P{w[+]=2A1}
Genetic reagent
(Drosophila mauritiana)		2P-5athis paperw[12], P{w[+]=2A1},
P{w[+]=ILEA1}
Genetic reagent
(Drosophila mauritiana)		2P-5bthis paperw[12], P{w[+]=2A1},
P{w[+]=2G3}
Genetic reagent
(Drosophila mauritiana)		2P-6athis paperw[12], P{w[+]=2G3},
P{w[+]=A1}
Genetic reagent
(Drosophila mauritiana)		2P-6bthis paperw[12], P{w[+]=ILEA1},
P{w[+]=A1}
Genetic reagent
(Drosophila mauritiana)		2P-7this paperw[12], P{w[+]=A1},
P{w[+]=3L1}
Genetic reagent
(Drosophila simulans)		YFP[175.2]PMID:28280212pBac{3XP3::EYFP-attP}
Genetic reagent
(Drosophila simulans)		YFP[356.5]PMID:28280212pBac{3XP3::EYFP-attP}
Genetic reagent
(Drosophila simulans)		YFP[377.31]PMID:28280212pBac{3XP3::EYFP-attP}
Genetic reagent
(Drosophila simulans)		YFP[52.4]PMID:28280212pBac{3XP3::EYFP-attP}
Genetic reagent
(Drosophila simulans)		YFP[277.1]PMID:28280212pBac{3XP3::EYFP-attP}
Genetic reagent
(Drosophila simulans)		YFP[926.3]PMID:28280212pBac{3XP3::EYFP-attP}
Genetic reagent
(Drosophila simulans)		YFP[16.3]PMID:28280212pBac{3XP3::EYFP-attP}
Genetic reagent
(Drosophila simulans)		YFP[360.1]PMID:28280212pBac{3XP3::EYFP-attP}
Genetic reagent
(Drosophila simulans)		YFP[433.1]PMID:28280212pBac{3XP3::EYFP-attP}
Genetic reagent
(Drosophila simulans)		YFP[19.1]PMID:28280212pBac{3XP3::EYFP-attP}
Genetic reagent
(Drosophila simulans)		YFP[21.4]PMID:28280212pBac{3XP3::EYFP-attP}
Genetic reagent
(Drosophila simulans)		YFP[458.6]PMID:28280212pBac{3XP3::EYFP-attP}
Sequence-based
reagent		Dox_F_1this paperCGAAATGAGACGCTTCTGTG
Sequence-based
reagent		Dox_R_1this paperAACCGATACCGTCGTAGTTGAC
Sequence-based
reagent		MDox_F_1this paperCCCATTTTGTCCAAGGTCAC
Sequence-based
reagent		MDox_R_2this paperAGTTCCGGTCAAAGTGGTTG
Sequence-based
reagent		RpS28b_F_1this paperTGGACAAACCAGTTGTGTGG
Sequence-based
reagent		RpS28b_R_1this paperAGGAACTCGACCTTCACCTG
Strain
(Drosophila simulans)		sim w[501]PMID:2293624914021–0251.011
Strain
(Drosophila simulans)		md06NCBI SRASRX497551
Strain
(Drosophila simulans)		md15NCBI SRASRX497574
Strain
(Drosophila simulans)		md63NCBI SRASRX497553
Strain
(Drosophila simulans)		md73NCBI SRASRX497563
Strain
(Drosophila simulans)		md105NCBI SRASRX497558
Strain
(Drosophila simulans)		md199NCBI SRASRX497559
Strain
(Drosophila simulans)		md221NCBI SRASRX495510
Strain
(Drosophila simulans)		md233NCBI SRASRX495507
Strain
(Drosophila simulans)		md251NCBI SRASRX497557
Strain
(Drosophila simulans)		ns05NCBI SRASRX497560
Strain
(Drosophila simulans)		ns33NCBI SRASRX497575
Strain
(Drosophila simulans)		ns39NCBI SRASRX497562
Strain
(Drosophila simulans)		ns40NCBI SRASRX497556
Strain
(Drosophila simulans)		ns50NCBI SRASRX497571
Strain
(Drosophila simulans)		ns67NCBI SRASRX497565
Strain
(Drosophila simulans)		ns78NCBI SRASRX497573
Strain
(Drosophila simulans)		ns79NCBI SRASRX497576
Strain
(Drosophila simulans)		ns113NCBI SRASRX497572
Strain
(Drosophila simulans)		ns137NCBI SRASRX497561
Strain
(Drosophila mauritiana)		r12NCBI SRASRX135546
Strain
(Drosophila mauritiana)		r23NCBI SRASRX688576
strain
(Drosophila mauritiana)		r31NCBI SRASRX688581
Strain
(Drosophila mauritiana)		r32NCBI SRASRX688583
Strain
(Drosophila mauritiana)		r39NCBI SRASRX688588
Strain
(Drosophila mauritiana)		r41NCBI SRASRX688609
Strain
(Drosophila mauritiana)		r44NCBI SRASRX688610
Strain
(Drosophila mauritiana)		r56NCBI SRASRX688612
Strain
(Drosophila mauritiana)		r61NCBI SRASRX688710
Strain
(Drosophila mauritiana)		r8NCBI SRASRX688712
Appendix 1—table 1
Gmin and power to detect simulated introgression on the X chromosome and autosomes.

Numbers in parentheses indicate the standard deviation from 100 replicate simulations

https://doi.org/10.7554/eLife.35468.034
400 ybp4000 ybp40,000 ybp
AXAXAX
Windows with migration (#)202.12 (18)31.06 (7.2)250.65 (16)66.48 (10)281.15 (20)65.22 (8.7)
Windows with migration (%)2.4% (0.21)1.7% (0.4)3% (0.19)3.7% (0.56)3.4% (0.24)3.6% (0.48)
Significant Gmin windows (#)179.08 (17)28.5 (6.4)111.44 (9.8)27.02 (4.7)15.87 (4.4)2.4
(1.3)
Significant Gmin windows (%)2.2% (0.2)1.6% (0.35)1.3% (0.12)1.5% (0.26)0.19% (0.052)0.13% (0.07)
True positive rate96% (1.5)95% (3.9)94% (2.4)93% (5.1)45% (11)30% (34)
False postive rate3.7% (1.5)4.8% (3.9)5.7% (2.4)6.8% (5.1)55% (11)70% (34)
Migration Events Detected85% (3.2)88% (7.5)42% (2.9)38% (5.1)2.6%
(1)		1.2% (1.4)
Appendix 1—table 2
X chromosome, and X/A ratio, for expectation of Patterson’s D.
https://doi.org/10.7554/eLife.35468.035
X/A ratio of NeRationaleE[D]X/A ratio of D
0.751:1 sex ratio, random mating, etc.0.0941.309
0.656Observed X/A nucleotide diversity in D. mauritiana0.1061.479
0.778Observed X/A nucleotide diversity in D. simulans0.0911.265

Additional files

Supplementary file 1

Gmin scan identifies forty-eight interspecific introgressions.

https://doi.org/10.7554/eLife.35468.029
Supplementary file 2

Genotype of samples at the Dox and MDox genes.

https://doi.org/10.7554/eLife.35468.030
Supplementary file 3

Primers used in RT-PCR to assay expression of MDox, Dox, and a control gene (RpS28b).

https://doi.org/10.7554/eLife.35468.031
Transparent reporting form
https://doi.org/10.7554/eLife.35468.032

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  1. Colin D Meiklejohn
  2. Emily L Landeen
  3. Kathleen E Gordon
  4. Thomas Rzatkiewicz
  5. Sarah B Kingan
  6. Anthony J Geneva
  7. Jeffrey P Vedanayagam
  8. Christina A Muirhead
  9. Daniel Garrigan
  10. David L Stern
  11. Daven C Presgraves
(2018)
Gene flow mediates the role of sex chromosome meiotic drive during complex speciation
eLife 7:e35468.
https://doi.org/10.7554/eLife.35468