7 April 2015
Origin, evolution, and population genetics of the selfish Segregation distorter gene duplication in European and African populations of Drosophila melanogaster
Cara L. Brand, Amanda M. Larracuente, and Daven C. Presgraves
Department of Biology University of Rochester Rochester, NY 14627 U.S.A
Word Count: 6,480 (Abstract: 172) Figures: 2 Tables: 5
Running title: Evolution of the selfish SD complex Keywords: meiotic drive, segregation distortion, Drosophila melanogaster, gene complex Corresponding Author: Cara L. Brand, Department of Biology, University of Rochester, Rochester, NY 14627 USA; Phone: (585) 276-2183; Email: [email protected]
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/evo.12658. This article is protected by copyright. All rights reserved.
1
ABSTRACT Meiotic drive elements are a special class of evolutionarily “selfish genes” that subvert Mendelian segregation to gain preferential transmission at the expense of homologous loci. Many drive elements appear to be maintained in populations as stable polymorphisms, their equilibrium frequencies determined by the balance between drive (increasing frequency) and selection (decreasing frequency). Here we show that a classic, seemingly balanced, drive system is instead characterized by frequent evolutionary turnover giving rise to dynamic, rather than stable, equilibrium frequencies. The autosomal Segregation Distorter (SD) system of the fruitfly Drosophila melanogaster is a selfish coadapted meiotic drive gene complex in which the major driver corresponds to a partial duplication of the gene RanGTPase activating protein (RanGAP). SD chromosomes segregate at similar, low frequencies of 1-5% in natural populations worldwide, consistent with a balanced polymorphism. Surprisingly, our population genetic analyses reveal evidence for parallel, independent selective sweeps of different SD chromosomes in populations on different continents. These findings suggest that, rather than persisting at a single stable equilibrium, SD chromosomes turn over frequently within populations.
This article is protected by copyright. All rights reserved.
2
INTRODUCTION Meiotic drive elements subvert the fair segregation of meiosis to gain a transmission advantage (Sandler and Novitski 1957; Zimmering, et al. 1970; Crow 1988). Once considered rare genetic curiosities, naturally occurring drive elements are now known to occur in a wide range of taxa (e.g., plants, fungi, insects and mammals), reside on sex chromosomes or on autosomes, and have far reaching consequences for the evolution of recombination, gametogenesis, genome structure, and speciation (reviewed in (Lyttle 1991; Jaenike 2001; Burt and Trivers 2006; Presgraves 2008; Meiklejohn and Tao 2010). Much of what is known about the genetics and molecular biology of drive comes from decades of work on two classic autosomal systems, the t-complex in house mouse species (Lyon and Phillips 1959; Silver 1985; Lyon 2003) and the Segregation Distorter (SD) complex of Drosophila melanogaster (Sandler, et al. 1959; Hartl 1975; Temin, et al. 1991; Kusano, et al. 2003; Larracuente and Presgraves 2012).
SD is found on 1-5% of second chromosomes (an autosome) in natural populations of D. melanogaster worldwide (Hiraizumi and Nakazima 1967; Hartl 1975; Temin and Marthas 1984; Temin, et al. 1991; Presgraves, et al. 2009; Larracuente and Presgraves 2012). SDmediated drive is male-specific: heterozygous SD/SD+ females transmit SD and SD+ chromosomes fairly, whereas heterozygous SD/SD+ males sire almost exclusively SD-bearing offspring (Sandler, et al. 1959). Soon after its discovery, genetic analyses revealed that SD corresponds to a multilocus gene complex comprising two major interacting loci and several linked upward modifiers of distortion (Sandler and Hiraizumi 1960; Hartl 1974). The Sd locus on chromosome arm 2L is a trans-acting driver that targets sensitive alleles at the cisacting locus, Responder (Rsp), on chromosome arm 2R. SD chromosomes carry Sd and drive-insensitive Rsp alleles (Rspi), whereas wildtype chromosomes lack Sd and tend to carry
This article is protected by copyright. All rights reserved.
3
drive-sensitive alleles (Rsps). Consequently, in Sd Rspi / Sd+ Rsps heterozygous males, the Sd+ Rsps sperm fail to develop properly and only Sd Rspi-bearing spermatids are transmitted to progeny. Sd encodes a truncated, tandem duplication of Ran-GTPase Activating Protein (RanGAP; hereafter Sd-RanGAP) (Merrill, et al. 1999), and Rsp corresponds to a block of 240-bp satellite repeats in the pericentric heterochromatin (Wu, et al. 1988; Pimpinelli & Dmitri 1989), with sensitivity to segregation distortion depending on Rsp repeat copy number (Rsps alleles comprise >700 copies, whereas Rspi comprise 10,000 coalescent simulations assuming a standard neutral model Probabilities obtained using >10,000 coalescent simulations assuming out-of-Africa bottleneck parameters of Thornton & Andolfatto (2006), see Materials & Methods b
This article is protected by copyright. All rights reserved.
35
Table 5. Strength of segregation distortion among SD chromosomes. Chromosome Armidale BN19 CN4 EC49 FR36 FR41 FR43 FR59 FR60 FR64 FR196 FR200 FR264 FR295 FR270 KM87 KM92 KN20 KR57 KY38 KY91 Las Arenas Madison MD21 MD31 NH2 NK04 Oviedo Roma SD72 SD79 SP188 VO17 WEY ZI86 ZI125 ZI138 ZI157 ZI233 ZI259 ZI323 ZI346 ZI348 ZI429 ZI469 ZI489 Z1517 ZL221 ZL304 ZL313 ZK216 ZO108
Male transmission
Female transmission
km
±s.e
km*
±s.e
Total progeny
kf
±s.e
Total progeny
1.000 0.575 0.452 1.000 0.877 0.993 0.999 0.984 0.851 0.996 0.987 0.899 0.999 0.955 0.932 1.000 1.000 1.000 0.500 1.000 1.000 0.907 0.980 1.000 0.522 0.991 1.000 0.957 1.000 1.000 1.000 1.000 0.989 1.000 1.000 1.000 1.000 0.545 1.000 1.000 1.000 0.496 1.000 0.529 1.000 0.531 0.518 1.000 0.547 0.501 1.000 0.529
0.000 0.004 0.000 0.000 0.011 0.000 0.000 0.000 0.013 0.000 0.000 0.008 0.000 0.002 0.003 0.000 0.000 0.000 0.000 0.000 0.000 0.002 0.000 0.000 0.000 0.000 0.000 0.003 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.002 0.000 0.000 0.000 0.002 0.000 0.000 0.000 0.001 0.003 0.000 0.000 0.002 0.000 0.000
1.000 0.493 0.425 1.000 0.870 0.989 0.998 0.984 0.771 0.996 0.982 0.880 0.998 0.940 0.927 1.000 1.000 1.000 0.405 1.000 1.000 0.871 0.973 1.000 0.392 0.986 1.000 0.947 1.000 1.000 1.000 1.000 0.984 1.000 1.000 1.000 1.000 0.441 1.000 1.000 1.000 0.495 1.000 0.433 1.000 0.516 0.453 1.000 0.513 0.431 1.000 0.460
0.000 0.004 0.000 0.000 0.012 0.000 0.000 0.000 0.030 0.000 0.000 0.011 0.000 0.004 0.004 0.000 0.000 0.000 0.000 0.000 0.000 0.003 0.000 0.000 0.000 0.000 0.000 0.005 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.002 0.000 0.000 0.000 0.002 0.000 0.000 0.000 0.001 0.003 0.000 0.000 0.002 0.000 0.000
2071 1179 1660 952 2023 2318 2157 1164 1351 2893 1564 2297 2010 2617 1986 1124 1092 1072 1655 837 1544 888 1178 997 1531 866 1167 830 193 686 878 585 1438 2300 1784 1119 995 1394 1424 517 1121 2527 775 2133 744 1694 1457 563 1196 1069 1307 1969
0.560 0.566 0.528 0.513 0.516 0.591 0.557 0.501 0.617 0.483 0.580 0.553 0.530 0.556 0.517 0.579 0.598 0.572 0.582 0.545 0.590 0.579 0.560 0.518 0.617 0.490 0.513 0.557 0.528 0.572 0.511 0.522 0.586 0.542 0.595 0.571 0.540 0.596 0.564 0.556 0.582 0.500 0.553 0.588 0.517 0.505 0.563 0.550 0.531 0.564 0.533 0.566
0.000 0.010 0.000 0.001 0.000 0.004 0.000 0.000 0.010 0.000 0.003 0.001 0.000 0.008 0.004 0.000 0.012 0.001 0.007 0.001 0.005 0.008 0.004 0.004 0.003 0.001 0.003 0.001 0.001 0.007 0.007 0.002 0.003 0.003 0.002 0.010 0.000 0.005 0.000 0.009 0.001 0.000 0.000 0.004 0.000 0.010 0.001 0.000 0.003 0.003 0.002 0.002
1457 561 454 428 807 427 303 245 999 277 1002 539 511 413 1045 430 799 1020 926 664 230 1539 1892 752 1167 706 457 1169 1035 529 646 278 2209 1117 672 283 153 116 692 123 528 140 529 782 751 395 445 249 307 1045 813 863
km = proportion progeny inheriting SD from SD/Gla males km* = proportion progeny inheriting SD from SD/Gla males, corrected for viability kf = proportion progeny inheriting SD from SD/Gla females
This article is protected by copyright. All rights reserved.
36
Origin, evolution, and population genetics of the selfish Segregation distorter gene duplication in European and African populations of Drosophila melanogaster
Cara L. Brand, Amanda M. Larracuente, and Daven C. Presgraves
Department of Biology University of Rochester Rochester, NY 14627 U.S.A
Word Count: 6,480 (Abstract: 172) Figures: 2 Tables: 5
Running title: Evolution of the selfish SD complex Keywords: meiotic drive, segregation distortion, Drosophila melanogaster, gene complex Corresponding Author: Cara L. Brand, Department of Biology, University of Rochester, Rochester, NY 14627 USA; Phone: (585) 276-2183; Email: [email protected]
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/evo.12658. This article is protected by copyright. All rights reserved.
1
ABSTRACT Meiotic drive elements are a special class of evolutionarily “selfish genes” that subvert Mendelian segregation to gain preferential transmission at the expense of homologous loci. Many drive elements appear to be maintained in populations as stable polymorphisms, their equilibrium frequencies determined by the balance between drive (increasing frequency) and selection (decreasing frequency). Here we show that a classic, seemingly balanced, drive system is instead characterized by frequent evolutionary turnover giving rise to dynamic, rather than stable, equilibrium frequencies. The autosomal Segregation Distorter (SD) system of the fruitfly Drosophila melanogaster is a selfish coadapted meiotic drive gene complex in which the major driver corresponds to a partial duplication of the gene RanGTPase activating protein (RanGAP). SD chromosomes segregate at similar, low frequencies of 1-5% in natural populations worldwide, consistent with a balanced polymorphism. Surprisingly, our population genetic analyses reveal evidence for parallel, independent selective sweeps of different SD chromosomes in populations on different continents. These findings suggest that, rather than persisting at a single stable equilibrium, SD chromosomes turn over frequently within populations.
This article is protected by copyright. All rights reserved.
2
INTRODUCTION Meiotic drive elements subvert the fair segregation of meiosis to gain a transmission advantage (Sandler and Novitski 1957; Zimmering, et al. 1970; Crow 1988). Once considered rare genetic curiosities, naturally occurring drive elements are now known to occur in a wide range of taxa (e.g., plants, fungi, insects and mammals), reside on sex chromosomes or on autosomes, and have far reaching consequences for the evolution of recombination, gametogenesis, genome structure, and speciation (reviewed in (Lyttle 1991; Jaenike 2001; Burt and Trivers 2006; Presgraves 2008; Meiklejohn and Tao 2010). Much of what is known about the genetics and molecular biology of drive comes from decades of work on two classic autosomal systems, the t-complex in house mouse species (Lyon and Phillips 1959; Silver 1985; Lyon 2003) and the Segregation Distorter (SD) complex of Drosophila melanogaster (Sandler, et al. 1959; Hartl 1975; Temin, et al. 1991; Kusano, et al. 2003; Larracuente and Presgraves 2012).
SD is found on 1-5% of second chromosomes (an autosome) in natural populations of D. melanogaster worldwide (Hiraizumi and Nakazima 1967; Hartl 1975; Temin and Marthas 1984; Temin, et al. 1991; Presgraves, et al. 2009; Larracuente and Presgraves 2012). SDmediated drive is male-specific: heterozygous SD/SD+ females transmit SD and SD+ chromosomes fairly, whereas heterozygous SD/SD+ males sire almost exclusively SD-bearing offspring (Sandler, et al. 1959). Soon after its discovery, genetic analyses revealed that SD corresponds to a multilocus gene complex comprising two major interacting loci and several linked upward modifiers of distortion (Sandler and Hiraizumi 1960; Hartl 1974). The Sd locus on chromosome arm 2L is a trans-acting driver that targets sensitive alleles at the cisacting locus, Responder (Rsp), on chromosome arm 2R. SD chromosomes carry Sd and drive-insensitive Rsp alleles (Rspi), whereas wildtype chromosomes lack Sd and tend to carry
This article is protected by copyright. All rights reserved.
3
drive-sensitive alleles (Rsps). Consequently, in Sd Rspi / Sd+ Rsps heterozygous males, the Sd+ Rsps sperm fail to develop properly and only Sd Rspi-bearing spermatids are transmitted to progeny. Sd encodes a truncated, tandem duplication of Ran-GTPase Activating Protein (RanGAP; hereafter Sd-RanGAP) (Merrill, et al. 1999), and Rsp corresponds to a block of 240-bp satellite repeats in the pericentric heterochromatin (Wu, et al. 1988; Pimpinelli & Dmitri 1989), with sensitivity to segregation distortion depending on Rsp repeat copy number (Rsps alleles comprise >700 copies, whereas Rspi comprise 10,000 coalescent simulations assuming a standard neutral model Probabilities obtained using >10,000 coalescent simulations assuming out-of-Africa bottleneck parameters of Thornton & Andolfatto (2006), see Materials & Methods b
This article is protected by copyright. All rights reserved.
35
Table 5. Strength of segregation distortion among SD chromosomes. Chromosome Armidale BN19 CN4 EC49 FR36 FR41 FR43 FR59 FR60 FR64 FR196 FR200 FR264 FR295 FR270 KM87 KM92 KN20 KR57 KY38 KY91 Las Arenas Madison MD21 MD31 NH2 NK04 Oviedo Roma SD72 SD79 SP188 VO17 WEY ZI86 ZI125 ZI138 ZI157 ZI233 ZI259 ZI323 ZI346 ZI348 ZI429 ZI469 ZI489 Z1517 ZL221 ZL304 ZL313 ZK216 ZO108
Male transmission
Female transmission
km
±s.e
km*
±s.e
Total progeny
kf
±s.e
Total progeny
1.000 0.575 0.452 1.000 0.877 0.993 0.999 0.984 0.851 0.996 0.987 0.899 0.999 0.955 0.932 1.000 1.000 1.000 0.500 1.000 1.000 0.907 0.980 1.000 0.522 0.991 1.000 0.957 1.000 1.000 1.000 1.000 0.989 1.000 1.000 1.000 1.000 0.545 1.000 1.000 1.000 0.496 1.000 0.529 1.000 0.531 0.518 1.000 0.547 0.501 1.000 0.529
0.000 0.004 0.000 0.000 0.011 0.000 0.000 0.000 0.013 0.000 0.000 0.008 0.000 0.002 0.003 0.000 0.000 0.000 0.000 0.000 0.000 0.002 0.000 0.000 0.000 0.000 0.000 0.003 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.002 0.000 0.000 0.000 0.002 0.000 0.000 0.000 0.001 0.003 0.000 0.000 0.002 0.000 0.000
1.000 0.493 0.425 1.000 0.870 0.989 0.998 0.984 0.771 0.996 0.982 0.880 0.998 0.940 0.927 1.000 1.000 1.000 0.405 1.000 1.000 0.871 0.973 1.000 0.392 0.986 1.000 0.947 1.000 1.000 1.000 1.000 0.984 1.000 1.000 1.000 1.000 0.441 1.000 1.000 1.000 0.495 1.000 0.433 1.000 0.516 0.453 1.000 0.513 0.431 1.000 0.460
0.000 0.004 0.000 0.000 0.012 0.000 0.000 0.000 0.030 0.000 0.000 0.011 0.000 0.004 0.004 0.000 0.000 0.000 0.000 0.000 0.000 0.003 0.000 0.000 0.000 0.000 0.000 0.005 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.002 0.000 0.000 0.000 0.002 0.000 0.000 0.000 0.001 0.003 0.000 0.000 0.002 0.000 0.000
2071 1179 1660 952 2023 2318 2157 1164 1351 2893 1564 2297 2010 2617 1986 1124 1092 1072 1655 837 1544 888 1178 997 1531 866 1167 830 193 686 878 585 1438 2300 1784 1119 995 1394 1424 517 1121 2527 775 2133 744 1694 1457 563 1196 1069 1307 1969
0.560 0.566 0.528 0.513 0.516 0.591 0.557 0.501 0.617 0.483 0.580 0.553 0.530 0.556 0.517 0.579 0.598 0.572 0.582 0.545 0.590 0.579 0.560 0.518 0.617 0.490 0.513 0.557 0.528 0.572 0.511 0.522 0.586 0.542 0.595 0.571 0.540 0.596 0.564 0.556 0.582 0.500 0.553 0.588 0.517 0.505 0.563 0.550 0.531 0.564 0.533 0.566
0.000 0.010 0.000 0.001 0.000 0.004 0.000 0.000 0.010 0.000 0.003 0.001 0.000 0.008 0.004 0.000 0.012 0.001 0.007 0.001 0.005 0.008 0.004 0.004 0.003 0.001 0.003 0.001 0.001 0.007 0.007 0.002 0.003 0.003 0.002 0.010 0.000 0.005 0.000 0.009 0.001 0.000 0.000 0.004 0.000 0.010 0.001 0.000 0.003 0.003 0.002 0.002
1457 561 454 428 807 427 303 245 999 277 1002 539 511 413 1045 430 799 1020 926 664 230 1539 1892 752 1167 706 457 1169 1035 529 646 278 2209 1117 672 283 153 116 692 123 528 140 529 782 751 395 445 249 307 1045 813 863
km = proportion progeny inheriting SD from SD/Gla males km* = proportion progeny inheriting SD from SD/Gla males, corrected for viability kf = proportion progeny inheriting SD from SD/Gla females
This article is protected by copyright. All rights reserved.
36
