Segregation distorters.

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SEGREGATION DISTORTERS Terrence W. Lyttle Department of Genetics and Molecular Biology, University of Hawaii, Manoa, Honolulu, Hawaii 96822 KEY WORDS:

gametogenesis. meiotic drive. sex ratio. segregation distortion , evolution of chromosome structure

CONTENTS INTRODUCTION . ......... . . . . . . . ........ . . . . . . ...... . . . . . . . . . ....... . . . . . . . ......... . . . . . . ........ .. What are Segregation Distorters? ... . . . . .... ... . . . . . . . . ... . ... . . . . . ......... .. . . . . . . ..... . . . .. Chromosomal Meiotic Drive . . " ................ "" ...................... """"....... ",,... Segregation Distorters as Examples of Genic Drive . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . Segregation Distorters as Ultraselfish DNA Elements . . . . . . . . . . . . . .. . . . . . . . . . . . . .. . . . .. . . . SEX CHROMOSOMAL VERSUS AUTOSOMAL DRIVE . ... . . . . . . . ...... . ............

Theoretical Analyses of Sex Chromosome Drive and Population Extinction . . . . . . . . . . Demographic Consequences of X versus Y Chromosome Drive.. . . . . . . . . . . . . . . . . . . . . . . . EVOLUTION OF SEGREGATION DISTORTION SYSTEMS ...... . . . . . . . . . .. . . . . . . . . ....

511 512 512 512 513 513 513 514 514

SEX RATIO DISTORTION IN NATURE. . . . ... . . . . . . . . . .. ..... . . . .. ...... . . . . . . . ....... . . . . ...

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AUTOSOMAL SEGREGATION DISTORTERS IN NATURE. .. . . ........ . . . . . . ....... . . . .

522 522 524 531 545

Spore-killer (Sk) in fungi . . . . . . . . . . . . . . . . . . .. . . . . . . . .. . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . .. . . . . . . . . . . . t-haplotypes in Mouse . . . . . . . . . . "................................................................ Segregation Distorter in Drosophila meianogaster ... . . . . . . . . .. . . . ... . . . . . ..... .. . . . ...... . A COMPARISON OF SEGREGATION DISTORTER SYSTEMS . . . . . . ....... . . . . . ...... .

INTRODUCTION

What Are Segregation Distorters? Segregation distorters are genetic elements that exhibit the phenomenon of meiotic drive; that is, the mechanics of the meiotic divisions cause one 511

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member of a pair of heterozygous alleles or heteromorphic chromosomes to be transmitted to progeny in excess of the expected Mendelian proportion of 50% ( 1 34, 1 36). In this review, we refer to these as genic or chromosomal drive, respectively. Genic meiotic drive is initially limited in its impact to the population dynamics of the drive locus itself and those loci fortuitiously in close linkage. Alleles at these latter loci may enjoy indirect drive through genetic hitchhiking, leading eventually to the establishment of drive haplo types (64). The haplotype may be extended by incorporating chromosome rearrangements that reduce recombination and promote further linkage dis equilibrium between the drive locus and more distant modifier loci ( 1 04, 1 28, 1 64). In the extreme , the haplotype becomes coextensive with the chromo some, leading to a form of chromosomal meiotic drive. For a parent heterozygous for either type of drive system, the statistic k is used to denote the proportion of progeny (and by inference, successful gametes) that carry the allele or chromosome exhibiting segregation distortion. Thus , k can vary from 0 . 5 (Mendelian segregation segregation) to 1 .0 (complete segregation distortion with only one gamete class recovered in the progeny) .

Chromosomal Meiotic Drive Chromosomal meiotic drive usually arises as a direct consequence of intrinsic chromosome structure rather than through the evolution of a drive locus and its linked modifiers . Chromosomal drive usually occurs in females, where an inherent asymmetry in oogenesis results in only one of the four products of meiosis being regularly functional. In many organisms, one of the two outermost of the four meiotic products becomes the functional egg. This product tends to include those chromosomes having an advantage in move ment on the spindle. Thus , the smaller member of a pair of asymmetrical dyads (36, 37 , 1 1 7), or those chromosomes carrying heterochromatic knobs exhibiting precocious movement along the spindle ( 1 3 1 ) , may each become included in ova in excess of Mendelian expectations. Genetic mechanisms in many plant and animal species favoring the accumulation of B chromosomes in one or both sexes (72, 73) , or specialized parasitic chromosomes that exploit haplo-diplo sex determination in some insects (e. g . Psr in the parasitic wasp- 1 80, 1 8 1 ) can also be loosely defined as examples of chromosomal drive. This form of drive is fairly nonspecific at the genetic level, arising as properties of whole chromosomes (e.g. extra replications) or at least large chromosomal segments, and is not considered further in this review .

Segregation Distorters as Examples of Genic Drive Segregation distorters comprise a group of systems of genic drive found in a wide range of organisms, usually involving a small number of interacting


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primary loci. Strictly speaking, segregation distorters are examples of gamete competition . This is because the excess recovery of the "driven" allele in the gametes of an individual is actually due to dysfunction or loss of a significant proportion of those gametes carrying the alternative allelic form. If this loss causes a strictly proportionate decrease in fecundity, essentially no meiotic drive results, because the "driven" allele participates in virtually the same number of fertilization events as would have occurred in the absence of gamete death (52) , and meiotic drive at the level of the individual parent produces no significant transmission advantage at the population level. Such real segregation advantage can arise only when; (a) competition occurs among gametes from single individuals (rather than in gamete pools of mixed paren tal origin, e.g. pollen competition on the stigma or Neurospora ascospores) , and (b) gamete loss results in a less than proportional loss of individual fecundity ( 1 1 1 ) . In short, establishment and increase of genic drive cannot be predicted from individual segregation ratios alone, but depends on an overall increase in the absolute number of progeny carrying the favored element from a heterozygous parent. Not surprisingly segregation distortion systems de pending on gamete competition are more likely to be found in males of monogamous species, where, gamete wastage has the smallest impact on fecundity .

Segregation Distorters as Ultraselfish DNA Elements Many segregation distorters can be described as "ultraselfish" DNA ( 1 7 , 1 90); that is, they not only show a tendency to increase in number or frequency without offering any fitness advantage to the organisms harboring them (as is also the case for "selfish" DNA-24, 1 1 9) , but in addition the driven element achieves this increase by actively promoting the destruction of its allelic alternative. Segregation distorters have been found in a wide range of organ isms, including plants in which species or strain hybrids have exhibited preferential dysfunction of gametes carrying one chromosomal class; this can occur in either pollen ( 1 1 , 26, 33, 87, 171), megaspores ( 1 39), or both ( 1 32). SEX CHROMOSOMAL VERSUS AUTOSOMAL DRIVE

Theoretical Analyses of Sex Chromosome Drive and Population Extinction Segregation distorters can be further divided into two groups depending on whether they are autosomal or sex-linked. B ecause males are the heteroga metic sex in many organisms and segregation distorters normally operate in spermatogenesis, we might expect sex chromosome drive to be common. Note, however, that even though both autosomal and sex-linked segregation distorters may reduce male fecundity and therefore impose a genetic load


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on average population fitness (60, 128, 148, 186-188), strong autosomal drive systems could, in theory, become fixed without any major detrimental effect on the population. A sufficiently strong sex-ratio distortion , however , may lead to population extinction (see computer simulations in Figure 1; 47) as a consequence of the elimination of one sex. As R. A. Fisher first noted (35), such sex ratio distortion is maladaptive at the level of the individual organism because it leads to the overproduction of the more common (and therefore less valuable) sex in his/her progeny. This , in tum, leads to a decreased mating success for the progeny as a group , and thus a reduced inclusive fitness (in terms of fewer grandchildren) for the original individual . Consequently, the effect of sex chromosome drive on population structure and individual fitness is generally of a much higher magnitude than for autosomal drive systems. For example, Hamilton (47) predicted that driving Y chromo somes spread faster through a population, and driving X chromosomes slow er, than does an autosomal element of similar drive strength restricted to acting in male meiosis (see Figures I and 2). This is because a driving Y chromosome is expressed in males in every generation, whereas a driving autosome finds itself in males only half the time, and a driving X chromosome only one third of the time.

Demographic Consequences of X versus Y Chromosome Drive Since the limiting factor for population fecundity is usually egg, not sperm, production, strong X chromosome drive may actually initially foster an increase in population size, whereas strong Y drive almost immediately causes a decrease in population size concomitant with the decrease in the proportion of females (see Figure 1 ) , producing an immediate detrimental effect on the population. Strong Y drive is of necessity transitory, since drive suppression must either evolve very quickly or the population will be pushed to extinction. This may explain why few Y drive systems have been observed in nature. Further , it has been suggested (47) that suppression of ancient Y chromosome drive systems may have been partially responsible for the heterochromatinization of the Y chromosome , or of autosomal segments that have become attached to the Y through translocation (cf Drosophila miranda- 1 56) . EVOLUTION OF SEGREGATION DISTORTION SYSTEMS The population genetics of meiotic drive has been extensively studied (15,27, 28 , 3 1 , 35 , 86, 97, 128 , 1 63 , 164, 166). Theoretical studies have provided information concerning the general evolutionary stability of Mendelian


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Figure 1 Changes in population size with sex chromosome drive. This depicts the expected deterministic results when a driving X or Y chromosome is introduced to an initial population comprised of \000 each X and Y chromosomes . In each case, it is assumed that all target chromosomes are sensitive to distortion, distortion is at level k = 1.0, and that males are capable of fertilizing two females. Note that Y drive produces an immediate population decline, ending in extinction at about generation 15, while X chromosome drive causes an initial population increase, p ostponing extinction beyond generation 40. The maximum population size and delay of extinction are both increased as the number of fertilizations allowed per male increases above two (after Hamilton-see ref. 47). Changes in frequency of the drive chromosomes in these two cases are represented more explicitly in Figure 2.

segregation and have led to specific predictions about the evolution of the segregation distorter loci, their target loci, modifiers of the strength of meiotic drive, and the linkage arrangements among these various elements . These predictions can be roughly summarized as follows. For genic drive to become established at all, there must be sufficiently tight linkage between the segrega tion distorter and its target locus to allow for the generation of linkage disequilibrium , with an excess of insensitive and sensitive target alleles in cis and trans, respectively, to the distorter allele (128). Linked modifiers of segregation distortion should also evolve linkage disequilibrium , with the drive allele found in coupling with enhancer and in repulsion with suppressor alleles at the same secondary modifier locus. The evolution of linked modi-

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Figure 2 Change in frequency of drive chromosomes over time. General conditions are as in Figure I. The curves for general X, Y and autosomal (A) drive are redrawn from Hamilton (47), assuming no diploid fitness differences among drive and nondrive chromosomes, and that segregation distortion is limited to one sex. Note that X drive is the least efficient, as discussed in the text. The curve for pY drive is compiled from actual data from Lyttle (see text under SD and ref. 92, 93), and follows the predicted path of Y drive closely, except at the end of the process where small population size introduces significant stochastic fluctuations.

fiers is dictated by their effects on the gametic fitness of sperm carrying the drive or target chromosomes. Other genetic factors (e.g. chromosome rear rangements such as inversions) may evolve to promote tighter linkage among the elements (104, 164). Two chromosomal "hap!otypes" eventually result , a favored form made up of the distorter allele, the insensitive target allele, and drive enhancers; the other consisting of the nondistorter combined with a sensitive target allele and drive suppressors. The susceptibility of the latter class of chromosomes to segregation distortion may be further reduced if sensitive target alleles are replaced by less sensitive forms (68, 106, 163), although these would be essentially indistinguishable from very closely l inked suppressors. This maintenance of tight linkage is extremely important because gene complexes, rather than single gene loci, are the genetic bases of all genic meiotic drive systems so far analyzed (190). Since recombination between the sex chromosomes of heteromorphic males is eliminated already (although recombination may occur in XX females), this makes it easy to establish drive



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haplotypes. We therefore expect sex chromosome drive to be , a priori , more common than autosomal drive, and this indeed appears to be the case in nature (48). Segregation distorters may affect organismal fitness indirectly, through the accidental fixation of linked (but unrelated) lethal or detrimental alleles . They can also lead to a direct loss of fecundity through gamete loss, or through a reduced production of grandchildren (35) in the case of sex chromosome drive. In either case there will be simple directional selection favoring fixation of unlinked suppressors of drive (94-96, 1 26, 165, 1 66, 1 7 5 , 1 88). Note that, in contrast to the linked modifiers discussed above. the evolution of such unlinked suppressors is dictated by selection at the level of the organism. That is , nonhomologous chromosomes gain no advantage from the excess transmission of the distorter gene complex, but share in any drop in diploid fitness arising from meiotic drive. Because a distorted sex ratio exerts such a significant negative effect on organismal fitness , unlinked modifiers of sex chromosome drive should be selected more rapidly than the corresponding modifiers of autosomal systems . When the mechanism of action of segregation distortion in a given sex affects homozygotes as well as heterozygotes , significant loss of homozygous fecundity can balance or even overcome a heterozygous gametic fitness advantage enjoyed by the distorter. This loss can be critical in determining the fate of autosomal drive systems (1 5); however, it clearly has little impact on sex chromosome drive, which is never homozygous in the heterogametic sex. When the distorter becomes secondarily linked to recessive lethals, homozy gous viability of both sexes becomes important. However , association of lethals with distorter systems should be selectively favored only when they allow for the removal and early reproductive compensation of otherwise sterile distorter homozygotes (see below on t-haplotypes in mousc-82-85). In summary , sex chromosomal and autosomal drive may have quite differ ent population genetic consequences. Sex chromosomal drive may have a higher a priori probability of occurring, owing to the ease with which linkage disequilibrium may arise between a distorter locus and its target. Once established, it should be more susceptible than autosomal drive to the accumulation of suppressors , but this susceptibility is partially offset by the fact that sex-ratio distorters avoid the negative effects of reduced homozygous fecundity often suffered by autosomal systems . SEX RATIO DISTORTION IN NATURE Four naturally occurring cases of sex ratio distortion caused by meiotic drive are known:

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1. X chromosome drive in the wood lemming In Myopus schisticolor (40), X chromosome variant apparently causes chromosomally XY males to develop as females; moreover, there is a preferential inclusion of the mutant X in the eggs produced by such females, promoting its increase in the popula tion. This results in a reduction in the sex ratio to as low as 20% males (k = 0.8) in some populations. 2. W chromosome drive in butterflies In several African butterfly species (where females are ZW, males ZZ) of the genera Danaus and Acraea, cases of W-chromosome drive have been observed that are often strong enough to produce unisexual female broods (13, 120, 154) (k = 1.0). For Danaus chrysippus, an autosomal locus (154), linked to loci controlling wing color and pattern, seems partially to suppress W drive by saving some Z-bearing gametes that also carry the proper suppressor allele. Evidence suggests that this suppressor variability may permit Danaus to use morph patterns as a cue for adjusting the sex ratio to track cyclical changes in the environment. 3. Male drive in mosquitoes In certain species of mosquitoes, sex is determined by a single locus on a largely homomorphic pair of sex chromo somes, with Mlm and mlm representing the male and female genotypes, respectively. Both Aedes aegypti and Culex quinquefasciatus harbor male distorter (MD) chromosomes, carrying a drive allele (D) at a locus which in Ae . Aegypti is closely linked to the sex determination locus (65) (map distance 1. 2%-113). Such chromosomes produce a sex ratio (k proportion male) as high as 0.99 in selected laboratory crosses (see Figure 3) (185). In nature, however, the effective sex ratio measured in 14 lines known to carry MD was in the range 0.499---0.606, as opposed to a control range of 0.486---0.550 obtained from 18 lines lacking the drive chromosome (I 22a). In Ae . aegypti, the suppression is a consequence of the presence of a range of MD chromo somes of varying sensitivity to segregation distortion in many wild pop ulations (183, 158). Some of these insensitive chromosomes carry an allele at a linked modifier locus (t) that apparently reduces the susceptibility of the X chromosome to MD-induced gamete dysfunction ( l 85a). Conversely, some MD chromosomes carry an enhancer (A) of drive located in the opposite arm from the suppressor. These linkage patterns accord with the theoretical pre dictions outlined above (104, 128, 164). In this system, D acts as the distorter locus, and m as a cis-acting target allele. However, while the progeny of MDlmd males are virtually all sons, MdlmD genotypes produce progeny with a normal sex ratio (65), suggesting that D does not produce a simple trans acting product. Figure 3 summarizes the genetic map of these several loci. Sperm dysfunction in mosquitos apparently arises as a consequence of the preferential breakage of the X chromosome, visible at the diplotene stage of male meiosis I, with breaks often located near sites of chiasma formation (112, 159, 184). Those few X-bearing spermatozoa that are produced often


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have organelles in an disintegrated state, and are presumably mostly nonfunc tional (185) . The biological mechanism for male drive is not yet established. Some cytological data concerning the gross DNA structure of the X and Y chromosomes is available, however. While the sex determining locus (M vs. m) has been placed near the centromere, the drive allele (D) has been localized to a region midway in one arm of the Y chromosome that often carries a large intercalary C band ( 1 13) (see Figure 3). The band is more common on X chromosomes although typically smaller; however, for both sex chromosomes it can be highly polymorphic in size. The region also differs between the sex chromosomes in staining patterns produced by quinacrine and Hoechst-33258 fluorochromes (178) , suggesting the possibility that the DNA base composition for this region may differ significantly between the two chromosomes, with the Y more AT-rich. At present, it is not possible to determine whether this association of the D allele with a cytogenetic polymorphism is purely fortuitous, represents a functional relationship, or indicates the nascent heterochromatinization of part of the Y chromosome. 4. X chromosome drive in Drosophila In contrast to the W or Y chromo some drive that occurs only among some butterfly or mosquito species, X chromosome drive occurs over a wide phylogenetic range of the genus Drosophila. Sex-Ratio (SR) chromosomes, as these driving X chromosomes are termed (110, 157), have been found in D . melanica and paramelanica (155), D . mediopunctata (20), D . quinaria and D . testacea (J. Jaenike, unpublished) of the subgenus Drosophila, and in many species in the sub genus Sophophora, including at least three species in the affinis subgroup (notably affinis and athabasca) and several species of the obscura group (azteca, obscura, pseudoobscura, and persimilis ( 1 1 6). In most of these species, SR chromosomes carry inversions distinguishing them from the standard X chromosome ( 189). These inversions most likely owe their evolu tion to their effect on reducing recombination between the as yet unidentified drive locus and linked drive enhancers. Males with the Sex-Ratio chromosome (Xr) transmit predominantly X bearing sperm, apparently owing to the degeneration of most Y-bearing sperm (63). In extreme cases, this degeneration leads to 1 00% female progeny (k 1.0). Provided that sperm are not limited, Xr should be transmitted at twice the rate of a normal X . As discussed above, in the absence of other forces, this transmission rate should lead to rapid fixation of Xr and concomitant popula tion extinction. Why does this not occur in natural populations, where the frequency of Xr reaches no higher than about 25% (in southeastern Arizona l57)? Two alternative explanations have been put forward. The first possibility is that Xr/Y males incur a reduction in fecundity roughly proportional to their reduced number of sperm. As noted above, such a correlation results in little or no transmission advantage at the population =

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==:=-:'"'::;;'===,so+ S alleles are considered. In males of genotype Dp(2 ;Y)SD; RspsfRspss, the absolute sur vival of sperm carrying either Rsp allele increases , apparently as a conse quence of diluting a limited Sd product. Nevertheless, the rclative recoveries of the two sperm classes appear to remain constant , i.e. no hierarchical dominance is evident for sensitivity to SD (e.g. the effect of SD is not directed only against the RspsS sperm class when both R�W' and RspsS sperm are present). Multiple Rsps or RspsS alleles may thus be functioning independent ly. However, recent results (Hiraizumi; unpublished data) suggest that in some genetic backgrounds SD acts preferentially against the more sensitive Rsp allele. Dp(2 ;Y)RspS; SD/SD + males carrying independently segregating copies of Rsps (linked to the Y and SD+ ) , produce sperm in predictable proportions with zero, one , or two Rsp" copies from the same male . The actual relative recovery proportions (r values) of these gametic classes suggests that , when together in the same sperm , two Rsps copies are synergistic in their effects on sperm dysfunction. Indeed, in experiments involving drive strengths for the SD test chromosome, sperm with two Rsp-' copies appear to have a much lower probability of survival than would be predicted i f each Rsps acted independently in causing sperm dysfunction ( 1 00). One possible explanation


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A threshold model for sperm dysfunction. This model is constructed for the SD system

of meiotic drive in D. melanogaster, although it might also apply to other segregation distorters. Sperm are assumed to have a quantitative underlying liability to sperm dysfunction, perhaps measured as time necessary to complete proper chromatin condensation. The presence of a sensitive target allele is assumed to displace the liability distribution of Rsps-bearing sperm to the right. The presence of the drive allele (SdJ is assumed to introduce a threshold (TJ for sperm

dysfunction (such that sperm from the shaded part of the distribution fail), or to move a preexisting threshold to the left along the X-axis . Drive modifiers act either to shift T slightly to the right (suppressors) or left (enhancers), or to shift the distribution of sperm liabilities in the opposite direction. A direct measure of the strength of drive is the probability of sperm dysfunction (r. defined in text), although the probit transformation can also be used to convert r values into M values. These have the desirable property of producing an additive measure of the action of genetic or environmental factors that change the relative displacement of sperm

liabilities with respect to the dysfunction threshold.

is that SD product is diffusible across the cytoplasmic bridges connecting syncytial sperm, and that sperm carrying multiple Rsps copies concentrates the limited SD product to a high degree ( lOO, 1 25). This would concomitantly intensify the SD "environment" for each of the individual Rsps copies, greatly increasing the probability for either to bind to SD, and thus geometrically increasing the overall probability of sperm dysfunction . This increased pro bability could occur even though each Rsps copy was, in a strict sense, reacting independently to SD . This effect was not observed in similar ex periments performed in Ganetzky's laboratory where small free duplications were used to provide the independently segregating second Rsps copy (9). However, the latter tests were performed only in relatively strong SD back ground, where survival probabilities for sperm carrying multiple Rsp alleles are always low and therefore difficult to estimate with confidence. Neverthe less, such contradictions must be resolved before the qualitative rules govern ing the interactions between multiple Rsp alleles can be precisely determined. Other genetic observations do not fit the view that sperm dysfunction arises solely as the consequence of the quantitative interaction between an SD product, present in limited amount , and one or more sensitive Rsp alleles . In particular , all models so far proposed for SD action , including Ganetzky' s ,


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are unable to explain why some SD homozygotes (or heterozygotes for different SD chromosomes) are male sterile (after excluding linked sterility alleles phenotypically and functionally unrelated to SD) and others fecund (50, 53, 60, 77) . In some cases, even males carrying triple doses of SD retain considerable fecundity, although the level does generally decline quantitative ly as the ratio of SD : Rspi alleles increases (7 , 42) (T. W . Lyttle, unpublished results) . Why are two doses of SD sufficient to cause sterility in some combinations , while three doses are fertile in other combinations? Con versely , if SD chromosomes have completely lost the Rsp region by deletion , as suggested by the cytological evidence discussed above ( 1 25) , why is this loss not sufficient to immunize SD chromosomes against segregation distor tion, so that SD homozygotes have normal spermatogenesis? One possibility may be genetic elements , as yet unidentified, capable of modifying the interaction of SD product with its own chromosome. For example the patterns of male sterility observed in genotypes made homozygous for various portions of the SD chromosome led Hiraizumi and coworkers (68 , 106) to suggest that a product of a secondary locus, M(SD) (which they have mapped to basal 2R), interacts with SD product to alter its affinity for the various Rsp allelic forms. Hiraizumi has suggested (67; unpublished data) that, in certain genetic backgrounds, M(SD) may cause negative distortion. This may perhaps be analogous to the negative distortion described earlier for certain genetic combinations in the t-haplotype system of meiotic drive in mouse. While Y -borne duplications of Sd and E(SD) together have an additive effect on the strength of segregation distortion , two independent studies ( 1 60; T. W. Lyttle, unpublished data) have demonstratcd that duplications of Sd alone have no effect on drive strength. These results suggest that Sd may act as a qualitative "trigger" whose presence is necessary only to initiate or qualitatively enhance the quantitative expression of E(SD) or other as yet unidentified loci. One possibility is that Sd and E(SD) together produce a protein complex that may bind to Rsp to mediate sperm dysfunction, and only the E(SD) product is present in rate-limiting amount. The likelihood that alleles other than Sd are playing a primary qualitative role in mediating segregation distortion is also suggested by two observations of what appear to be multiple Sd loci. In one case, the secondary locus maps near to the original Sd mutation, although it is separable from it by recombination (58) . A second putative locus ( 1 45) (called Sd2) appears to map to the 2L-centric heterochro matin , near E(SD). Arguments for the existence of both these loci are based on observations that certain SD chromosomes, which have lost Sd by recombination, may still exhibit low, but persistent levels of meiotic drive; however, other studies have demonstrated that SD chromosomes that have lost Sd by irradiation-induced deletion events usually show no such residual drive (7). Results from recent experiments by Temin ( 1 60) and unpublished observations of this laboratory may resolve this conundrum. These results ,



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demonstrate that E(SD), even in the absence of Sd, may generate low levels of drive if present in a background genome carrying a sufficient number of other drive enhancers, or if tested against a target chromosome carrying a super sensitive Rsp allele (Rsp-''') . Thus, under some conditions , E(SD) may behave as if it were Sd2 • Clearly, neither of the putative secondary loci share significant DNA homology with Sd, as defined molecularly by Powers ( 1 6 1 ) , so i t i s problematic as to whether they should employ the Sd label . How ever, the fact that more than one locus may be capable of causing segre gation distortion means that the model of a monomeric Sd product binding at Rsps to cause sperm dysfunction , while heuristic, may be an oversimpli fication . Mutations of Rsp" to Rspi (probably deletions, based on the known DNA structure of RW') can instantly convert SD + chromosomes from sensitivity into insensitivity. An ongoing evolutionary puzzle of the SD system is why, in the absence of any obvious normal function for RW', populations of D . melanogaster should simultane ously maintain high frequencies of both sensitive Rsp alleles (50-80% or more) and SD ( 1-3%) (5 1 , 56, 5 7 , 59, 70, 73, 1 62, 1 63 , 1 69 , 1 70), especially when such sensitive Rsp alleles are maintained at only very low equilibrium frequencies in laboratory populations segregating for SD (57, 69) . Several earlier studies invoking transposable elements (45, 66) as playing a role in both the action and population dynamics of SD elements are less tenable given our current understanding of the molecular structure of Sd and Rsp . A more plausible explanation is that Rsp' is maintained because it does have a positive impact on fitness, but its contribution is too small to measure under normal laboratory conditions . To test this notion , Wu and coworkers ( 1 92) took advantage of the existence of RSpi chromosomes, viable as homozygotes, which have been produced by small X-ray-induced heterochromatic deletions of an otherwise genetically identical RW' parent chromosome (42). They monitored laboratory populations (size = 5 ,000) of D. melanogaster segregating for such RSpi and Rsps second chromosomes. Over one year, the frequency of the RSpi chromosome in the cages dropped to 1 0% from an initial value of nearly 40% . Rsps alleles may therefore have a fitness advantage over their RSpi counterparts over the long term; however, other sequences deleted along with Rsps may be primarily responsible for the fitness differences. Further, the possibility of a normal function for Rsp' satellite DNA sequences is hard to reconcile with the very low copy number of XbaI repeats detected in other D rosophila species examined. The putative normal function may be provided by a similarly expanded repeat array that diners sufficiently in sequence as to remain undetected by the XbaI repeat probe. In addition to the obvious source of suppression of segregation distortion arising from deletion or alteration of Rsps to give RSpi, a number of studies SUPPRESSORS OF SEGREGATION DISTORTION


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have identified additional X-linked and autosomal suppressors of SD activity arising in natural populations of Drosophila melanogaster (5 1 , 55 , 70, 74, 132, 1 67), as well as enhancer loci linked to the SD chromosome by inversion complexes (60) . Very little is known about these modifiers , which are mostly not even well mapped, although a major X suppressor, present at frequencies as high as 85% in some populations, has been localized to the vicinity of the vermillion (v) gene (74), and there is also a major suppressor linked to the third chromosome balancer TM6 (99). Usually, these modifiers behave as additively acting polygenes . However, some may show epistatic interactions with SD . In one study , a third chromosome modifier, which acted as an enhancer of a sympatric SD, became a suppressor when tested with an allopatric SD ( 1 69) , while a second study has reported SD + chromosomes that were insensitive to strong sympatric SD homologs, but sensitive to weaker allopatric SD ' s ( 146). Recent evidence (Grigliatti , personal communication) suggests that modifi ers of position effect variegation (PEV), which effect the expression of heterochromatic genes, may also reduce the sensitivity of Rsp alleles to SD . This observation further implies that the SD-Rsp interaction may be sensitive to changes in chromatin condensation or compaction, and thus provide a clue to the nature of some SD modifiers . Conversely, SD suppressors may be good candidates for modifiers of PEV . Because SD is an autsomal drive system that generates relatively weak selection for suppressors, the slow rate of evolution for the latter is difficult to observe directly in experiments using laboratory populations. However, by manipulating the SD system to cause distorted sex ratios, the rate of evolution of these same suppressors can be significantly enhanced. To this end, Lyttle (94-96) translocated a portion of an SD autosome onto the Y chromosome to produce a form of Y chromosome drive (called pseudo- Y, or pY drive) . This was not true Y chromosome drive, because segregation distortion was still directed against SD+ , and not the X chromosome (see Figure 3), but its impact on the population and the evolution of genetic suppression was comparable to that of a Y -drive system. Lyttle (94-96) established a number of laboratory populations with a mixture of pY-drive and normal males. These not only provided experimental verification of the impact of sex ratio distortion on population demographics (see Figure 2) , but the strong selective pressure favoring suppression of male drive acted as an evolutionary hothouse in forcing a more rapid accumulation of drive suppressors than occurs for SD in its normal autosomal form . The strength of pY-drive in the lines used to establish these populations varied from k 0.94 to k 1 . 00; that is, from 94% to exclusive production of sons from pY-drive fathers . Since the absolute number of such sons exceeded the number produced by normal males from the same population , pY-drive continued to increase in frequency among males, and the overall population =

=


545

sex ratio was pushed further away from the optimal I : I value until it reached the intrinsic sex ratio of the pY-drive line itself. For strong pY-drive, this led to rapid population extinction owing to lack of females , usually within 7-8 generations. The dynamics of population extinction followed a path very close to that predicted for Y chromosome drive in Figure 2. Normal males were eventually eliminated even in cages harboring weaker pY-drive lines (initial k = 0.94); however, the persistence of low frequencies of females ( 6%) prevented population extinction . These populations were monitored for more than 40 generations, during which time the strength of drive (and the sex ratio) declined slowly and linearly with time, as measured by M values. The observed decrease in drive strength could be attributed to polygenic , quantitatively acting suppressors , each of small effect, distributed across both the X and non-SD autosomes . The SD chromosomes themselves accumulated drive enhancers , as also would be predicted by popUlation genetic theory (see above) . In one population , however, sex ratio distortion was rapidly neutralized by the accumulation of sex chromosome aneuploids (XXY females and XYY males), with the sex ratio stabilizing at =60% male. This occurs because, under pY drive, sex ratio distortion arises because daughters normally die through lack of a Y chromosome, thus aneuploids carrying extra Y chromosomes are a source of significant numbers of surviv ing XXY daughters. For this population , since segregation distortion no longer affected sex ratio , selection for drive suppressors ceased (96). In general , the cage results suggest that conditions favoring the accumula tion of drive suppressors (e .g. weak distortion , slow population extinction) are insufficient for maintaining aneuploidy, while conditions favoring an euploidy (e .g. strong distortion , very low production of females) lead to population extinction before polygenic drive suppressors can accumulate. Thus, the different mechanisms for neutralizing sex-ratio distortion are com plementary in action . Now that both X and Y chromosomes exist that carry the Rsps target DNA sequences (see above), the SD system rather than pY -drive can be used to produce true X and Y chromosome drive in the laboratory. Use of the SD system should lead to a better understanding of the population dynamics of sex ratio distortion , as well as to a more detailed general mapping, and perhaps ultimately the DNA structure, of specific drive suppressor genes.


=

A COMPARISON OF SEGREGATION DISTORTER SYSTEMS

At first glance, the structure and mechanisms for these five systems of segregation distortion seem very similar. In fact, just such a comparison was made in detail for t-haplotypes and SD by participants at the Edinburgh Symposium on the Genetics of the Spermatozoon, some twenty years ago (6) .


546

LYTTLE

Table 1 summarizes the results of a similar comparison , expanded by the addition of the three other drive systems covered here , and supplemented by subsequent knowledge. All systems involve alleles at a minimum of two closely linked loci , a distorter and its cis-acting target (although this is currently only a working hypothesis for Neurospora, and awaits direct veri fication) . All are associated with polymorphisms of chromosome structure, usually inversions linked to the drive chromosome itself. All involve gamete dysfunction as the basic modus operandi. Finally, each "host" organism has accumulated analogous classes of insensitive target alleles and suppressor/ enhancer polymorph isms as means of inactivating these ultraselfish genetic systems. These similarities can be best interpreted as the result of convergent evolution dictated by the population genetic constraints operating on gamete killers (as described above) . Such convergences are largely independent of the biological mcchanism by which segregation distortion occurs. Hence, when the systems are examined in more detail at the level of their biological (or, where possible, molecular) mechanisms , the similarities appear less pro nounced. In fact, at the DNA level , the only apparent similarity may lie in the common association that elements from several of the distorter systems (t, SD, MD, and perhaps Sk) have with regions of centromeric heterochromatin or repetitive DNA . However, this may simply reflect the fact that the general ly reduced recombination in heterochromatin makes it easier to establish multilocus drive systems. Sk can be most easily split off from the four animal systems. Despite being limited to action in one sex (males) , significant reductions in total sperm can be tolerated in these gamete-killing systems without proportional losses in fecundity. Because the absolute number of successful sperm carrying the segregation distorter is increased above the level obtained in the absence of drive , these systems yield a significant transmission advantage favoring their rapid increase in frequency in a popUlation. However, Sk activity does not enjoy a similar advantage-the total number of "successful" Sk spores from Ski+ parents remains constant, irrespective of whether the + allele is sensi tive or resistant to Sk action. Strictly speaking, the magnitude of increase in Sk frequency will thus depend solely on the decrease in population gamete number deriving from the loss of + spores. When Sk is rare (as would be the case for a new mutation), its impact on spore production is negligible. Thus , realized drive is weak relative to stochastic sampling effects in all but the largest populations (i.e. those on the order of billions of individuals with initial Sk frequency of p 0.000 1 ) , and there is virtually no effective meiotic drive at the population level (c .f. the earlier discussion under Segregation Distorters as Examples of Genic Drive) . This may explain why, although Sk is among the strongest of the segregation distorters , most Sk alleles are apparent1y disappearing from natural populations of Neurospora. The observations that the presence of Sk saves a gamete, not the absence of the + allele, and =

547

SEGREGATION DISTORTERS Table 1

A comparison of drive systems. Drive system

Phenomenon SD

SR

O M

Sk

Mode of action A

A

X

Y

A

+a

+

+

+

+

E

L

E

E

L

Limited to males

+

+

+

+

NA

Sensitive target causes gamete dysfunction

+

+

+

+

+ +

Target locus cis-acting

+ +

+ +

+ ?d

+

Distorter locus tran s - acting

+ +

R/S

S, L

R

na

+ /-

>99%

90-99%

>99%

50-6 1 %

+

+

X, Y or autosomal (A) drive Mode of action


(E

=

=

gamete dysfunction

early visible gamete abnormalities, L

=

late)

Insensitive target rescues gamete

Homozygous effects (S

R

=

=

male sterility,

reduced fertility, L

=

lethality)

Degree of distortion in nature

>99%

Genetic and population structure DNA sequence information

+

Evidence for transcription of target sequences

+

Heterochromatic elements involved

+

+

Drive elements linked to centromere

+

+

+

+

+/-

Linked chromosome rearrangements

+

+

+

+

+ /-

Drive and target loci recombinationally separable

+

+

+

+

+

Trans-acting modifiers present

+

System widespread in natural populations

+

+/ +

+

c

+ +

+ /-

+ indicates presence of the phenomenon represents its absence I indicates differences among strains or species d ? indicates no information available a

b

-

C

that SklSk homozygotes exhibit normal gametogenesis, combine to further suggest a biological mechanism for this system different from the other autosomal distorter systems, where the presence of the cis-acting sensitive target alleles causes gamete dysfunction in distorter males , and where distor ter homozygotes usually show severely reduced fecundity .


548

LYTTLE

Despite the relative paucity of detailed genetic information, the MD system can be separated from the other three animal systems primarily in that the distorter allele is not trans-acting. MD and SD do exhibit some similarities, however. Both show abnormalities as early as Meiosis I, and both systems have alleles associated with size polymorphisms for AT-rich chromosomal bands, although the drive allele (D) in the MD system, in contrast to the target allele (RW') of the SD system, maps to the AT-rich regions. However, MD appears to rely on a mechanism involving chromosome breakage, while SD seems to cause abnormal chromatin condensation in sensitive sperm . The two Drosophila systems and t-haplotypes have important similarities . They each appear t o b e ubiquitous i n their respective species, indicating their evolutionary success. Apparently , each system may involve multiple, trans acting distorter elements . Generally , the elements seem to largely interact quantitatively, although , in the SD system at least, the Sd allele may have a unique qualitative role ( 1 60 , 1 6 1 ) . All three systems, along with MD, operate by promoting the dysfunction of a sperm class carrying a sensitive target allele; to accomplish this, each system seems to key on postmeiotic genetic differences among sperm that can be maintained in spite of syncytial cyto plasm among sperm arising from the same primary spermatocyte . For SD and t-haplotypes, negative segregation distortion (where the normally insensitive target allele (RSpi or Rt) is recovered in sperm less often than the sensitive target allele (RspS or R t » occurs in certain genetic backgrounds (67 , 9 1 ) . This negative distortion indicates the presence of significant epistatic interactions in these systems . Although the Y -linked target locus for segregation distortion i n SR i s as yet unknown, the biological and molecular mechanisms of SD and t-haplotypes apparently differ considerably . While SD depends on a general failure of target sperm to accomplish individualization, probably due to abnormal chro matin condensation, the lesions in defective sperm from tl+ mice are more subtle, perhaps involving only a premature triggering of the acrosome reac tion ( 10) . Further, the target locus for SD is apparently a noncoding region of repetitive DNA ( 1 9 1 ) (although the Rsp region may be transcribed in a manner analogous to the Y-loops of many Drosophila species-46). This observation is compatible with the notion that the target locus acts as a DNA binding site for proteins regulating chromatin condensation. Conversely, while the target locus (Tc�) for t-haplotypes appears to be one of a family of DNA repeats , it apparently codes for a transcribed , translated testis-specific mRNA that is nonetheless cis-acting ( 1 37), making it perhaps only super ficially analogous to Rsp in the SD system. The population dynamics of the several systems may also differ significant ly. Sk shows weak effective drive and suppression is expected to occur rapidly by the selection of insensitive target alleles (although other interesting bio-



549

logical adaptations may have arisen to avoid spore-killers, as discussed above-1 74) . While SR is apparently strong in natural populations, a surpris ing result for an X-chromosome drive system, it may actually be similar to Sk in that it may exhibit a low effective meiotic drive because of a loss in fecundity of SR males ( 1 90) . On the other hand, MD is generally weak in natural mosquito populations, as expected for Y-chromosome drive systems, which would otherwise significantly affect realized fecundity. Recently , meiotic drive has been conjectured to promote hybrid sterility ( 3 9 , 7 1 ) , and therefore have an important role in speciation. That is, if allopatric pop ulations evolve independent, complementary sex chromosomal drive systems, hybrid males between them could be rendered sterile . Such a scenario has been offered as an explanation for Haldane' s rule (i. e . the heterogametic sex is usually sterile or missing in the progeny of a hybrid cross) . This is very close to the suggestion discussed above that the evolution from eight to four-spore asci in some fungi may have been a mechanism to escape hybrid sterility resulting from meiotic drive. Again, the two autosomal systems, SD in Drosophila and t-haplotype in mouse, seem to be the most similar in their population dynamics. Both are maintained in stable polymorphisms in nature ( 1-3% for SD , 1 0-20% for t-haplotypes), yet the frequencies for both are lower than might be predicted from theory developed using estimates of drive and fitness parameters as determined in the laboratory. In SD , this is due both to the presence of drive suppressors in natural populations (7 1 , 1 63) and to the likely existence of a small intrinsic selective disadvantage (independent of segregation distortion) for insensitive target alleles ( 1 92) , while for t-haplotypes , this seems to be a consequence of demic (83) or behavioral (8 1 ) selection acting against the distorter in nature . For both systems , distorter chromosomes are often associ ated with recessive sterility and/or lethality. However, although all ( haplotype homozygotes are male sterile (as a consequence of interaction of Tedt alleles) and most are lethal (78 , 149) , many SD homozygotes are viable and fertile ( 1 63). If an intrinsic sterility is associated with t-haplotype homozygosity , then reproductive compensation of aborted embryonic lethals superimposed on a background of kin selection operating in small demes (84) may explain why there is actually a selective advantage for t-haplotypes to accumulate recessive embryonic lethals . There is no equivalent reason why SD chromosomes should do so. The existing lethals may simply have become established in a mechanism like Muller's ratchet (32); that is, by the chance fixation of lethal mutations in haplotypes largely closed to recombination and subject to strong genetic drift. Segregation distortion may be responsible for the high frequency of several recessive lethals identified in several screens of D. melanogaster populations (23 , 153). In summary, meiotic drive in general , and genic systems of segregation


550

LYTTLE

distortion in particular, exist in a wide range of organisms. As information on the best-studied systems accumulates , their apparently great similarities seem to stem from convergent evolution resulting from common population genetic pressures. Conversely, the biological (and molecular) mechanisms involved in segregation distortion appear to involve different aspects of gametogenesi s . This observation serves to highlight the surprising but inevitable question regarding this wide range of meiotic drive mechanisms: Why is Mendelian segregation evolutionarily stable? For, as Crow so succinctly stated ( 1 7) , "Mendelism i s a magnificent invention for fairly testing genes in many combinations, like an elegant factorial experimental design. Yet it is vulner able at many points and is in constant danger of subversion by cheaters that seem particularly adept at finding such points. " ACKNOWLEDGMENTS

Many individuals contributed thoughtful criticisms of draft versions of this manuscript and were generous in providing unpublished thoughts and data. The author wishes to particularly thank James F. Crow and Larry Sandler (to whom this review is dedicated) for many stimulating discussions of the genetic basis and population consequences of meiotic drive. David Perkins, B arbara Turner, Roger J . Wood, and Chung-I Wu helped me enormously in sorting out the notational and biological differences among drive systems in different organisms. Bruce B aker was of great help in ferreting out and correcting ambiguities and downright errors . Any remaining mistakes are mine alone. This work was supported by grant 58-9 1 H2-6-42 from the Agricultural Research Service of the USDA, and grants DCB-87 1 5984 and DCB-85 1 7504 from the National Science Foundation. Literature Cited 1 . Aquadro, C. F . , Susan, S. F . , Bland, M. L . , Langley. C. H .. Laurie. C. C . 1 986. Molecular population genetics of the alchohol dehydrogenase gene region of Drosophila melanogaster, Genetics 1 14: 1 1 65-90 2 . Beckenbach , A. T. 1 978. The Sex-Ratio trait in Drosophila pseudoobscura : fertility relations of males and meiotic drive. Am. Nat. 1 1 2:97- 1 1 7 3 . Beckenbach, A . T . 1 983. Fitness analy sis of the Sex-Ratio polymorphism in experimental populations of Drosophila pseudoobscura. Am. Nat. 1 2 1 :630--48 4. Beckenbach, A. T. 1 99 1 . "Sex-ratio" in the Drosophila obscura group. Am. Nat. 1 37:340--3 5. Beckenbach, A. T . , Curtsinger, C. W . , Po1icansky, D. 1 982. Fruitless ex periments with fruitflies: The sex-ratio

chromosomes of Drosophila pseudoob scura. Dros. Inf. Servo 58:22 6. Braden, A. W. H . , Erickson, R . P . , Gluecksohn-Wae1sch, S . , Hartl, D . L . , Peacock, W. J . , Sandler, L. 1972 . A comparison of effects and properties of segregation distorting alleles in the mouse (I) and in Drosophila (SD). I n Edinburgh Symposium o n the Genetics of the Spermatozoon, ed. R. A. Beatty , S. Gluecksohn-Waelsch, pp. 3 1 0-- 1 2. Bogtrykkeriet Forum, Copenhagen 7. Brittnacher, J. G . , Ganetzky , B . 1 983. On the components of Segregation dis tortion in Drosophila melanogaster. II. Deletion mapping and dosage analysis of the SD locus. Genetics 1 03 :659-73 8. Brittnacher, J. G . , Ganetzky, B . 1 984. On the components of Segregation dis tortion in Drosophila melanogaster.

SEGREGAnON DISTORTERS III. Nature of Enhancer of SD. Genetics

9.


10.

11.

12.

13.

14. 15.

16. 17. 1 7a .

18.

19.

20.

21.

22.

1 97:423-34 Brittnacher, J. G . , Ganetzky, B . 1 989. On the components of Segregation dis tortion in Drosophila melanogaster. IV Con struction and analysis of free du plications for the R:,p locus. Genetics 1 2 1 :739-50 Brown, J . , Cebra-Thomas, J. A . ,Bleil, 1 . D . , Wassarman, P. M . , Silver, L. M. 1989. A premature acrosome reaction is programmed by mouse t haplotypes dur ing sperm differentiation and could play a role in transmission ratio distortion. Development 106:769-73 Cameron, D. R . , Moav, R. 1957. In heritance in Nicotiana tabacum. XXVII. Pollen killer, an alien genetic locus inducing abortion of microspores not carrying it. Genetics 42:326-35 Campbell, J . c . , Turner, B. C . 1987. Recombination block in the Spore killer region of Neurospora. Genome 29 : 1 2935 Chanter, A. 0 . , Owen, D. F . 1 97 2 . The inheritance and population genetics of sex ratio in the butterfly Acraea en cedon . J. Zool . 166: 363-83 Ch arlesworth , B . 1 98 8 . Driving genes and chromosomes. Nature 332:394-95 Charlesworth, B . , Hartl, D. L. 1978. Population dynamics of the Segregation Di storter polymorphis m of Drosophila melanogaster. Genetics 89: 1 7 1 -92 Crow, J. F. 1 979. Genes that violate Mendel's rules. Sci . A m . 240: 1 34-46 Crow, J. F. 1 988. The ultraselfish gene. Genetics 1 1 8:389-9 1 Crow, 1. F. 1 99 1 . Why is mendelian segregation so exact? BioEssays 1 3 : 1 8 Curtsinger, J. W. 198 ! . Artificial selec tion on the sex ratio in Drosophila pseudoobscura. J. Hered. 72:377-8 1 Curts inger , 1. W . , Feldman, M. W. 1980. Experimental and theoretical anal yses of the "sex-ratio" polymorphism in Drosophila pseudoobscura . Genetics 94: 445-66 De Carvalho, A. B . , Peixoto, A. A . , K1aczko, L . B . 1 989. Sex ratio i n Dro sophila mediopunctata . Heredity 62: 425-28 Delarbre, C . , Kashi, Y . , Boursot, P . , B eckmann, J. S . , Kourilsky, P . , et al. 1 98 8 . Phylogenetic distribution in the gcnus Mus of Homplcx-specific DNA and protein markers: Inferences on the origin of t-hap1otypes. Mol. Bioi. Evol. 5 : 1 20-33 de Magalhaes, L. E . , Roveroni, 1. M . , Campos, S . H . A . 1 985. Occurrence of the sex-ratio trait in natural populations

55 1

of Drosophila simulans in Brazil. Rev. Brasil. Genet. 8(3):449-56 23. Dominguez, A . , Albomoz, J . , Santiago, E. 1 987. Analys is of lethals in selected lines of Drosophila melanogaster. Thear. App l . Genet. 74:409- 1 3 24. Doolittle, W . F . , S apienza , C. 1 980. Selfish genes, the phenotype paradigm and genome ev olution . Nature 284:6013 25. Doshi , P . , Kaushal , S . , Benyajati, C . , Wu, C-1. 1 99 1 . Molecular analysis of the Responder satellite DNA in Dro sophila melanogaster: DNA bending, nucleosome structure and Rsp-binding proteins. Genetics. In press 26. Endo, T. R. 1982. Gametocida\ chromo somes of three Aegi/ops species in com mon wheat. Can. J. Genet. Cytol. 24: 20 1 -6 27 . Eshel, I. 1985 . Evolutionary genetic stability of Mendelian segregation and the role of free recombination in the chromosomal system. Am. Nat. 1 25 : 4 l 2-20 28. Eshel, 1. , Feldman , M. W. 1 982. On the evolutionary genetic stability of the sex ratio. Theor. Populo BioI. 2 1 :430-39 29. Esser, K. 1 974. Podospora anserina. In Handbook of Genetics, ed. R. C . King, 1 : 53 1-55. New York: Plenum 30. Faulhaber, S. H. 1 967. An abnormal sex-ratio in Drosophila simulans. Genet ics 56:1 89-2 1 3 3 1 . Feldman, M . W . , Otto, S . P . ; 99 1 . A comparative approach to the population genetic theory of segregation distortion. Am. Nat. 1 37 :443-56 32. Felsenstein, J. 1 974. The evolutionary advantage of recombination. Genetics 78:737-56 33. Finch, R. A . , Miller, T. E. , Bennett , M . D . 1 984. "Cu ckoo" Aegilops addition chromosome in wheat ensures its transmission by causing chromosome breaks in meiospores l acking it. Chro mosoma 90:84-88 34. Finney , D . J. 1 97 1 . Probit Analysis. Cambridg e : Cambridge Univ. Press 35. Fisher, R. A . 1 930. The Genetical Theory of Natural Selection . Oxford: Oxford Univ. Pre s s . 2 9 1 pp. 36. Foster, G. G . , Whitten, M. J. 1 974. Unequ al segregation in Lucilia cuprina. Genetics 77:s22-s23 37. Foster, G . G . , Wh itte n , M . J. 1 99 1 . Meiotic drive in Lucilia cuprina and c hromo somal evolution. Am. Nat. 137:403- 1 5 3 8 . Fox, H . S . , Martin, G . R. , Lyon, M . F . , Herrmann , B . , e t al . 1 985. Molecular probes define d ifferent regions of the mouse t-complex. Cell 40:63-69

552

LYTTLE

Frank, S. A. 1 99 1 . Divergence of meio tic drive-suppression systems as an ex planation for sex-biased hybrid sterility and inviability. Evolution 45:262-67 40. Fredga, K . , Gropp, A . , Winking, H . , Frank, F. 1 977. A hypothesis explaining 39.

41.


42.

43 .

44. 45 .

46.

47. 48.

49.

the exceptional sex ratio in the wood lemming (Myopus schisticolor) . Heredi tas 85 : 1 01-4 Frischauf, A . M . 1985. The Tit complex of the mouse. Trends Genet. 1 : 1 00-3 G an etzky , B. 1977. On the components of Segregation distortion in Drosophila melanogaster. Genetics 86:321-55 Gatti, M . , Pimpinelli, S . , Santini, G. 1 976. Characterization of Drosophila heterochromatin . 1. Staining and de condensation with Hoechst 33258 and Quinacrine. Chromosoma 75:35 1-75 Deleted in proof Golic, K. 1985. A modification of segregation distortion that suggests that the elements affecting distortion are transposable. Genetics I IO:s23 Hackstein, J . H . P. 1 987. Sperma togenesis in Drosophi l a . In Sperma togenesis: Genetic Aspects, ed. W. Hennig, pp. 63- 1 1 6 . Berlin: Springer Verlag Hamilton, W. D. 1967. Extraordinary sex ratios. Science 1 56:477-88 Hammer, M. F. 1 99 1 . Molecular and chromosomal studies on the origin of t haplotypes . Am. Nat. 1 37:359-65 Hammer, M. F . , Schimenti, J . , Silver, L. M. 1989 . Evulution of mouse chromosome 17 and the origin of in versions associated with t haplotypes. Proc. Natl. Acad. Sci. USA 86:326 1 65

Hartl, D. L. 1 969. Dysfunctional sperm production in Drosophila melanogaster males homozygous for the Segregation distorter elements. Proc. Natl. Acad. Sci. USA 63:782-89 5 1 . Hartl, D. L. 1 970. Meiotic drive in nat ural populations of Drosophila melano gaster . IX. Suppressors of Segregation Distorter in wild populations. Can. 1. Genet. Cytol. 1 2:594-600 52. Hartl, D. L. 1972. Population dynamics of sperm and pollen killers. Theor. Appl. Genet. 42:81-88 53. Hartl, D . L. 1973 . Complementation analysis of male fertility among the Segregation distorter chromosomes in Drosophila melanogaster. Genetics 50.

73:613-29

54. 55.

Deleted in proof Hartl, D. L. 1 975. Modifier theory and meiotic drive. Theor. Popul o BioI. 7:

56.

Hartl,

1 68-74

D. L.

1977.

How does the

genome congeal? In Measuring Selec tion in Natural Populations, ed. F. B . Christiansen, T . M . Fenchel, pp. 65-82. New York: Springer-Verlag 57. Hartl, D. L. 1 977. Mechanism of a case of genetic coadaptation in populations of Drosophila melanogaster. Proc. Natl . Acad. Sci. USA 74:32+-28 5 8 . Hartl, D. L. 1 980. Genetic dissection of Segregation distortion. III. Unequal recovery of reciprocal recombinants. Genetics 96:685-96 59. Hartl, D. L . , Hartung, N. 1 975 . High frequency of one element of Segregation Distorter in natural populations of Dro sophila melanogaster. Evolution 29: 5 1 2- 1 8

Hartl, D . L . , Hiraizumi, Y . 1 976. Segregation Distortion after fifteen years. In The Genetics alld Biology of Drosophila, ed. M. Ashburner, E. Novitski, I B : 6 1 5-66. New York: Aca demic. 954 pp. 6 1 . Hartl, D. L . , Hiraizumi, Y . , Crow, J . F. 1 967. Evidence for sperm dysfunction as the mechanism of segreg ation distortion in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 58:2240-45 62. Hauschteck-Jungen, E . , Hartl. D. L. 1 982. Defective histone transition dur ing spermiogenesis in heterozygous Segregation-Distorter males of Dro

60.

sophila melallogaster. Genetics

1 0 1 :57-

69

Hauschteck-Jungen, E . , Maurer, B . 1976. Sperm dysfunctiou in sex ratio males of Drosophila subobscura . Gene tica 46:459-77 64. Hedrick, P. W. 1988. Can segregation distortio n influence gametic disequilibri um? Genet. Res . , Camb. 52:237-42 65 . Hickey, D. A . , Loverre, A. , Carmody, G . 1 986. Is the Segreg ation distortion phenomenon in Drosophila due to recur rent active ge netic transpos ition ? Genet 63.

ics

66.

67.

67a.

68.

69.

1 14:665-68

Hickey, W. A . , Craig, G. B . 1 966. Ge netic distortion of sex ratio in mosquito, Aedes aegypti. Gelletics 53: 1 1 77-96 Hiraizumi, Y . 1989 . A possible case of negative segregatiou distortion in the SD system of Drosophila melallogaster. Ge netics 1 2 1 :263-71 Hiraizumi, Y. 1 990. Negative segrega tion distortion in the SD system of Dro sophila melallogaster: a challenge to the concept of differential sensitivi ty of Rsp alleles. Genetics 1 25 : 5 1 5-25 Hiraizumi, Y . , Martin, D. W . , Eck strand, I. A. 1 980. A modified model of Segregation Distortion in Drosophila melanogaster. Genetics 95:693-706 Hiraizumi, Y . , Sandler, L . , Crow, J. F.

SEGREGATION DISTORTERS 1 960. Meiotic drive in natural pop� ulations of Drosophila melanogaster III. Population implications of the Segregation�distorter locus. Evolution

83. Lewontin, R . C . 1 962. Interdeme selec 84.

24:41 5-23

70. Hiraizumi, Y . , Thomas, A. M. 1984.

70a.


71.

72. 73. 74.

Suppressor systems of Segregation Dis� torter (SD) chromosomes in natural pop� ulations of Drosophila melanogaster. Genetics 106:279-92 Hull, P. 1964. Partial incompatibility not affecting total litter size in the mouse. Genetics 50:563-70 Hurst, L . , Pomiankowski, A. 1 99 1 . Causes o f sex ratio bias may account for unisexual sterility in hybrids: A new ex� planation of Haldane's Rule and related phenomena. Genetics. In press Jones, R. N. 1 99 1 . B chromosome drive. Am. Nat. 1 37:43�2 Jones, R. N . , Rees, H. 1 982 . B Chromosomes. New York: Academic. 266 pp. Kataoka, Y. 1967. A genetic system modifying Segregation distortion in a natural population of Drosophila me� lanogaster in Japan. lpn . l. Genet.

42:327-37

75. Kathariou , S . , Spieth, P. T. 1 982. Spore

killer polymorphism in Fusarium moni� liforme. Genetics 102: 1 9-24 76. Kettaneh, N. P . , Hartl, D. L. 1 976. His� tone transition during spermiogenesis is absent in Segregation Distorter males of Drosophila melanogaster. Science 193:

1020--2 1 7 7 . Kettaneh, N . P . , Hartl, D . L. 1 980. UI�

trastructural analysis of spermiogenesis in Segregation distorter males of Dro� sophila melanogaster: The homozy� gotes. Generics 96:665-83 78. Klein, J . ,Sipos, P . , Figueroa, F. 1 984. Polymorphism of t� complex genes in European wild mice. Genet. Res. 44:39-

46 79. Langley , C. H . , Aquadro, C. F. 1987.

Restriction map variation in natural pop� ulations of Drosophila melanogaster: white locus region. Mol. Bioi. Evo!.

4:65 1-63 80. Lenington, S . , Franks, P . , Williams, J . 1 988. Distribution o f t � haplotypes i n natural populations o f wild house mice. J. Mammal. 69:489-99 8 1 . Lenington, S . , Heisler, I . L. 1 99 1 . Be havioral reduction of transmission of de leterious r haplotypes by wild house mice. Am. Nat. 1 37:366-78 82. Levine, L . , Rockwell, R. F . , Gross� field, J. 1980. Sexual selection in mice. V. Reproductive competition between +1+ and +ltw5 males. Am. Nat. 1 16:

1 50--5 6

553

85.

86.

87.

88.

89. 90.

tion controlling a polymorphism in the house mouse. Am. Nat. 96:65-78 Lewontin, R. C. 1 968. The effect of differential viability on the population dynamics of t alleles in the house mouse. Evolution 22:262-73 Lewontin, R. C . , Dunn, L. C. 1960. The evolutionary dynamics of a polymorphism in the house mouse. Ge netics 45:705-22 Lieberman, U. 1976. Theory of meiotic drive: Is Mendelian segregation stable? Theor. Populo Bioi. 10: 1 27-32 Logering, W. Q . , Sears, E. R. 1 963 . Distorted inheritance of stem-rust resis tance of Timstein wheat caused by a pollen�killing gene . Can. l. Genet. Cytol. 5:65-72 Lyon, M. F. 1 984. Transmission ratio distortion in mouse t-haplotypes is due to multiple distorter genes acting on a responder locus. Cell 37:621-28 Lyon, M. F. 1986. Male sterility of the mouse t�complex is due to homozygosity of the distorter genes. Cell 44:357-63 Lyon, M. F. 1 987. Distorter genes of the mouse t-complex impair male fertility when heterozygous. Genet. Res. 49:57-

60 9 1 . Lyon, M. F. 1 99 1 . The genetic basis of transmission ratio distortion and male sterility due to the t-complex. Am. Nat.

1 37:349-58 92. Lyon, M. F . , Zenthon, J. 1987. Differ�

ences in or near the responder region of complete and partial mouse t haplotypes . Genet. Res. Camb. 50:29-

34 93. Lyon, M. F. , Zenthon, J . , Evans, E. P . ,

Burtenshaw, M . D . , Willison, K . R . 1988. Extent o f the mouse t complex and its inversions shown by in situ hybridiza tion. Immunogenetics 27:375-82 94. Lyttle , T. W. 1 977. Experimental pop ulation genetics of meiotic drive sys tems. I. Pseudo-Y chromosomal drive as a means of eliminating cage populations of Drosophila melanogaster. Genetics

86:413-45 95 . Lyttle, T. W. 1 979. Experimental pop

ulation genetics of meiotic drive sys tems. II. Accumulation of genetic mod ifiers of Segregation distorter (SD) in laboratory populations. Genetics

9 1 :339-57 96. Lyttle, T. W. 1 98 1 . Experimental pop

ulation genetics of meiotic drive sys tems. III . Neutralization of sex�ratio dis� tortion in Drosophila through sex chromosome aneuploidy. Genetics 98:

3 1 7-34 97. Lyttle, T.

W.

1 982. A theoretical

554

98 .

99.


100.

101 . 102.

103.

LYTTLE analysis of the effects of sex chromo some aneuploidy on X and Y chromo some drive. Evolution 36:822-3 1 Lyttle, T. W. 1 984. Chromosomal con trol of fertility in Drosophila melanogas ter. I. Rescue of T(Y; A)/bbI/58 male sterility by chromosome rearrangement. Genetics 106:423-34 Lyttle, T. W. 1986. Additive effects of multiple Segregation Distorter (SD) chromosomes on sperm dysfunction in Drosophila melanogaster. Genetics 1 14: 203- 1 6 Lyttle, T. W. 1989. The effect o f novel chromosome position and variable dose on the genetic behavior of the Responder (Rsp) element of the Segregation Distor ter (SD) system of Drosophila melano gaster. Genetics 1 2 1 :75 1-63 Deleted in proof Lyttle, T. W . , Brittnacher, 1. G . , Ganetzky , B . 1986. Detection o f Rsp and modifier variation in the meiotic drive system Segregation Distorter (SD) of Drosophila melanogaster. Genetics 1 1 4: 1 83-202 Lyttle, T. W . , Wu , C. I . , Hawley, R. S . 1 99 1 . Molecular analysis o f insect meiosis and sex ratio distortion. In

Molecular Approaches to Pure and Ap plied Entomology, ed. M. J. Whitten, J. 1 04.

105.

106.

1 07 .

108.

109.

1 1 0.

G . Oakeshott. Berlin: Springer-Verlag. In press Maffi , G . , Jayakar, S. D. 1 98 1 . A two locus model for polymorphism for sex linked meiotic drive modifiers with possible applications to Aedes aegypti. Theor. Populo Bioi. 19: 1 9-36 Mange, E. J. 1968. Temperature sensitivity of Segregation distortion in Drosophila melanogaster. Genetics 58: 399-4 1 3 Martin, D. W . , Hiraizumi, Y . 1 979. On the models of Segregation Distortion in Drosophila melanogaster. Genetics 93: 423-35 Miklos, G. L. G. 1972. An investigation of the components of Segregation distor ter in Drosophila melanogaster. Genet ics 70:405- 1 8 Miklos, G . L . G . 1985. Localized high ly repetitive DNA sequences in ver tebrate and invertebrate genomes. In Molecular Evolutionary Genetics, ed. R. J. MacIntyre, pp. 241-32 1 . New York: Plenum Miklos, G. L. G . , Smith-White, S . 1972. A n analysis o f the instability of Segregation distorter in Drosophila melanogaster. Genetics 67:305- 1 7 Morgan, T. H . , Bridges, C. B . , Sturte vant, A. H. 1925 . The genetics of Dro sophila. Bibliogr. Genet. 2 : 1 -262

I l l . Mulcahy, D. L. 1 975. The biological significance of gamete competition. In Gamete Competition in Plants and An imals, ed. D. L. Mulcahy, pp. 1-3. Am sterdam: North-Holland 1 1 2. Newton, M. E. , Wood, R. J . , Southern, D. I. 1976. A cytogenetic analysis of meiotic drive in the mosquito, Aedes aegypti (L. ) . Genetica 45:297-3 1 8 1 1 3 . Newton, M . E . , Wood, R. J . , Southern, D. I . 1 978. Cytological mapping of the M and D loci in the mosquito, Aedes aegypti (L.). Genetica 48: 1 37-43 1 1 4. Nicoletti, B . , Trippa, G . , DeMarco, A . 1 967. Reduced fertility i n SD males and its bearing on segregation distortion in Drosophila melanogaster. Atti Accad. Naz. Lincei Cl. Sci. Fis. Mat. Nat. Rend. 43:383-92 1 1 5 . Nolan, J. M . , Lee, M. P . , Wyckoff. E . , Hsieh, T-S. 1986. Isolation and characterization of the gene encoding Drosophila DNA topoisomerase II. Proc. Natl. Acad. Sci. USA 83:3664-68 1 1 6. Novitski, E. 1 947. Genetic analysis of an anomalous sex ratio condition in Dro sophila affinis. Genetics 32:526--34 1 1 7 . Novitski, E. 1967. Nonrandom disjunc tion in Drosophila. Annu. Rev. Genet. \ :7 1-86 1 1 8 . Olds-Clarke, P. , Peitz, B. 1 985. Fertil ity of sperm from t/+ mice: evidence that +-bearing sperm are dysfunctional. Genet. Res. 47:49-52 1 1 9. Orgel , L. E . , Crick, F. H. C. 1980. Selfish DNA: The ultimate parasite. Na ture 284:604-7 120. Owen, D . F. 1974. Seasonal change in sex ratio in Acraea quirina (F.) (Lep. Nymphalidae) , and notes on the factors causing distortions of sex ratio in butterflies. Entomol. Scand. 5 : 1 1 0-- 1 4 1 2 1 . Padieu, E . , Bernet, 1 . 1977. Mode d'ac tion des genes responsibles de I ' avorte ment de certains produits de la meiose chez I' ascomycete Podospora anserina. C. R. Acad. Sci. Ser. D 264:2300--3 1 22. Peacock , W. J . , Tokuyasu , K. T. , Har dy, R. W. 1972. Spermiogenesis and meiotic drive in Drosophila. See Ref. 6 , p p . 247-58 1 22a. Pearson, A. M . , Wood, R. J. 1980. Combining the meiotic drive gene D and the translocation TI in the mosquito A edes aegypti (L.) Chromosoma 67: 253-6 1 1 23 . Perkins, D. D . , B arry , E. G . 1977. The cytogenetics of Neurospora . Adv. Genet. 1 9 : 1 33-285 1 24. Petras, M. L. 1967. Studies of natural populations of Mus. II. Polymorphism at the T locus. Evolution 2 1 :466--7 8 125. Pimpinelli, S . , Dimitri, P. 1 989.


SEGREGATION DISTORTERS Cytogenetic analysis of the Responder (Rsp) locus in Drosophila melanogaster. Genetics 1 2 1 :765-72 1 26. Policansky, D . , Dempsey, B. B . 1978. Modifiers and Sex Ratio in Drosophila pseudoobscura. Evolution 32:922-24 1 27 . Deleted in proof 1 28 . Prout, T. , Bundgaard, J . , Bryant, S . 1973. Population genetics o f modifiers of meiotic drive. I . The solution of a special case and some general im plications. Theor. Populo Bioi. 4:446-65 1 29 . Raju, N. B. 1979. Cytogenetic behavior of Spore killer genes in Neurospora. Ge netics 93 :607-23 1 30. Rappold, G. A . , Stubbs, L . , Labeit, S . , Crkvenjakov, R . B . , Lehrach, H . 1987. Identification of a testes-specific gene from the mouse t-complex next to a CpG-rich island. EMBO J. 6: 1 975-80 1 3 1 . Rhoades, M. M . , Dempsey, E. 1 966. The effect of abnormal chromosome 1 0 o n preferential segregation and crossing over in maize. Genetics 53:989-1020 1 32 . Rick, C. M. 1 966. Abortion of male and female gametes in the tomato de termined by allelic interaction. Genetics 53:85-96 1 3 3 . Sandler, L . , Carpenter, A. T. C. 1 972. A note on the chromosomal site of action of SD in Drosophila melanogaster. See Ref. 6, pp. 233-46 1 34. Sandler, L . , Golic, K. 1 985. Segrega tion distortion in Drosophila. Trends Genet. 1 : 1 8 1-85 1 3 5 . Sandler, L . , Hiraizumi , Y . , Sandler, I . 1 959. Meiotic drive in natural pop ulations of Drosophila melanogaster. I . The cytogenetic basis o f segregation distortion. Genetics 44:233-50 1 36. Sandler, L . , Novitski, E. 1 957. Meiotic drive as an evolutionary force. Am. Nat. 4 1 : 1 05-10 1 37 . Schimenti, J . , Cebra-Thomas, J . A . , Decker, C . L. , Islam, S . D . , Pilder, S . H . , Silver, L. M . 1 988. A candidate gene family for the muuse t complex responder (Tcr) locus responsible for haploid effects on sperm function. Cell 55:7 1-78 1 3 8 . Schimenti, J . , Void, J . , Socolow, D. , Silver, L. M. 1 987 . An unstable family of large DNA elements in the center of the mouse t complex. J. Mol. Bioi. 1 94:583-94 1 39. Scoles, G. J . , Kibirge-Sebunya, I. N . 1 983. Preferential abortion o f gametes i n wheat induced b y a n Agropyron chromo some. Can. J. Genet. Cytol. 25: 1-6 140. Seitz, A. W . , Bennett, D. 1 985 . Transmission distortion of t haplotypes is due to interactions between meiotic partners. Nature 3 1 3 : 1 43-44

555

1 4 1 . Sharp, C . B . , Hilliker, A . J . 1 986. Measuring segregation distorion in Dro sophila melanogaster. Can. J. Genet. Cyto!. 28:395-400 142. Sharp, C. B . , Hilliker, A. J. 1 987 . The k-probit transformation and segregation distortion. Dros. [nf. Servo 66: 1 27-28 143. Sharp, C. B . , Hilliker, A. 1. 1 989. Link age and segregation distortion in Dro sophila melunogaster. Genome 32: 84046 1 44. Sharp, C. B . , Hilliker, A. J. 1 99 1 . Segregation ratios within Segregation distorter lines of Drosophila melanogas ter conform to a beta-binomial distribu tion. Genet. Res. Camb. 5 5 : 1 65-70 145. Sharp, C. B . , Hilliker, A. J . , Holm, D . G . 1985 . Further characterization o f ge netic elements associated with the Segregation distorter phenomenon in

Drosophila 1 46.

147.

148. 149. 150.

lSI.

1 52 .

153. 1 54.

155.

melanogaster.

Genetics

1 1 0:671-88 Shimakawa, E. S. 1 987. A molecular and population genetic study of Segrega tion distorter in Drosophila melanogas ter. PhD thesis. Univ. Hawaii, Manoa Shin, H. S . , McCormick , P . , Artzt, K . , Bennett, D. 1 983. Cis-trans test shows a functional relationship between non allelic lethal mutations in the Tit com plex. Cell 33:925-29 Silver, L. M. 1982. Genomic analysis of the H-2 complex region associated with mouse t haplotypes . Cell 29:961-68 Silver, L. M. 1 985. Mouse t haplotypes. Annu. Rev. Genet. 1 9 : 1 79-208 Silver, L. M . , Hammer, M . , Fox, H . ,Garrcls, J . , Buchan, M . , et al. 1987 . Molecular evidence for the rapid pro pagation of mouse t haplotypes from a single, recent ancestral chromosome. Mol. Bioi. Evo!. 4:473-82 Silver, L. M . , Olds-Clarke, P. 1 984. Transmission ratio distortion of mouse t haplotypes is not a consequence of wild type _sperm degeneration . Dev. Bioi. 105:250-52 Silver, L. M . , Remis, D. 1987 . Five of the nine genetically defined regions of mouse t haplotypes are involved in transmission ratio distortion. Genet. Res. Comb. 49: 5 1 -56 Skibinski, D . O . F. 1986. Study of lethals in selection lines in Drosophila melanogaster. J. Hered. 77:3 1-34 Smith, D. A. S. 1 975 . All-female broods in the polymorphic butterfly Danaus chrysippus and their ecological significance. Heredity 34:363-7 1 Stalker, H. D. 1 96 1 . The genetic sys tems modifying meiotic drive in D ro sophila paramelanica. Genetics 46: 1 77202


556

LYTTLE

1 56. Steinemann, M. 1982. Multiple sex chromosomes in Drosophila miranda: A system to study the degeneration of a chromosome. Chromosoma 86:59-76 1 57 . Sturtevant, A. H . , Dobzhansky, T. 1936. Geographical distribution and cytology of "sex-ratio" in Drosophila pseudoobscura and related species. Ge netics 2 1 :473-90 1 5 8 . Suguna, S. G . , Wood, R. J . , Curtis, C. F. , Whitelaw, A., Kazmi, S . J . 1977. Resistance to meiotic drive at the MD locus in an Indian wild population of Aedes aegypti. Genet. Res. 29: 1 23-32 159. Sweeney, T. L . , Barr , A. R. 1978. Sex ratio distortion caused by meiotic drive in a mosquito, Culex pipiens (L.). Ge netics 88:427-46 1 60. Temin, R. G. 1 99 1 . The independent distorting ability of the Enhancer of Segregation distortion, E(SD) , in Dro sophila melanogaster. Genetics. 1 28: 339-56 1 6 1 . Temin, R. G . , Ganetzky, B . , Powers, P. A . , Lyttle, T. W . , Pimpinelli, S . , et al. 1 99 1 . Segregation distorter (SD) in Dro sophila melanogaster: Genetic and molecular analyses. Am. Nat. 1 37:287331 162. Temin, R . G . , Kreber, R. 1 98 1 . A look at SD in the wild population in Madison, Wisconsin, more than 20 years after its initial discovery there. Dros. Inf. Servo 56: 1 37 163. Temin, R. G . , Marthas, M. 1984. Fac tors influencing the effect of Segregation distortion in natural populations of Dro sophila melanogaster. Genetics \07: 375-93 1 64. Thomson, G. J . , Feldman, M. W. 1 974. Population genetics of modifiers of meiotic drive. II Linkage modification in the Segregation distortion system. Theor. Populo Bioi. 5: 1 55-62 165. Thomson, G. J . , Feldman, M . W. 1 975. Population genetics of modifiers of meiotic drive. III Equilibrium analysis of a general model for the genetic con trol of segregation distortion. Theor. Populo BioI. 1 0: 1 0-25 166. Thomson, G . J . , Feldman, M . W. 1976. Population genetics of modifiers of meiotic drive. IV. On the evolution of Sex-ratio distortion. Theor. Populo Bioi. 8:202- 1 1 1 67. Tokuyasu, K. T . , Peacock, W. J . , Har dy, R. W. 1 972. Dynamics of sper miogenesis in Drosophila melanogaster. I. Individualization process. Z. Zell forsch. 1 24 :479-506 1 68. Tokuyasu, K. T . , Peacock, W. J . , Har dy, R. W. 1 977. Dynamics of sper miogenesis in Drosophila melanogaster.

169.

1 70.

171.

1 72. 173.

174. 1 75 .

176.

1 77 .

178.

1 79.

1 80.

181. 1 82.

VII. Effects of Segregation distorter chromosome. J. Ultrastruct. Res. 58: 96-107 Trippa, G . , Loverre, A. 1 975. A factor on a wild third chromosome (IIIRa) that modifies the Segregation distortion phe nomenon in Drosophila melanogaster. Genet. Res. 26: 1 1 3-25 Trippa, G . , Loverre, A . , Ciccetti, R . 1980. Cytogenetic analysis of a n SD chromosome from a natural population of Drosophila melanogaster. Genetics 95:399-4 1 2 Tsujimoto, H . , Tsunewaki, K . 1 985. Gametocidal genes in wheat and its rela tives. II. Suppressor of the chromosome 3C gametocidal gene of Aegilops triun eialis. Can. J. Genet. Cytol. 27: 1 78-85 Turner, B. C. 1 977. Resistance to Spore killer genes in Neurospora strains from nature. Genetics 86:s65-s66 Turner, B. C . , Perkins, D. D. 1979. Spore killer, a chromosomal factor in Neurospora that kills meiotic products not containing it. Genetics 93:587-606 Turner, B. C . , Perkins, D. D. 1 991 . Meiotic drive in Neurospora and other fungi . Am. Nat. 1 37:41 6-29 Uyenoyama, M. K. , Feldman, M. W. 1 978. The genetics of sex ratio distortion by cytoplasmic infection under maternal and contagious transmission: An epide miological study. Theor. Pop. Bioi. 14:47 1-97 Voelker, R. A. 1 972. Preliminary characterization of "sex-ratio" and rediscovery and reinterpretation of "male sex ratio" in Drosophila affinis. Genetics 7 1 :W597-606 Walker, E. S . , Lyttle, T. W . , Lucchesi, J. C. 1989. Transposition of the Respon der element (Rsp) of the Segregation dis torter system (SD) to the X chromosome in Drosophila melanogaster. Genetics 1 22:8 1-86 Wallace, A. J . , Newton, M. E. 1 987. Heterochromatin diversity and cyclic re sponses to selective silver staining in Aedes aegypti (L.). Chromosoma 95:8993 Wallace, B. 1948. Studies on "sex ratio" in Drosophila pseudoobscural. Selection and "sex-ratio". Evolution 2 : 1 89-2 1 7 Werren, J . , Nur, U . , Eickbush, D . 1987. A n extrachromosomal factor caus ing loss of paternal chromosomes. Na lure 327:75-76 Werren, J. H. 1 99 1 . The Psr (Paternal sex ratio) chromosome. Am. Nat. 137:392-402 Willison, K. R . , Dudley, K . , Potter, J . 1986. Molecular cloning and sequence


SEGREGA nON DISTORTERS analysis of a haploid expressed gene encoding t complex polypeptide I . Cell 44:727-38 1 8 3 . Wood. R. J. 1 976. Between-family var iation in sex ratio in the Trinidad (T30) strain of Aedes aegypti (L.) indicating differences in sensitivity to the meiotic drive gene MD . Genetica 46:345-6 1 1 84. Wood. R. J . , Newton, M . E. 1 977. Meiotic drive and sex ratio distortion in the mosquito Aedes aegypti. Proc. Plen. Symp . , Genet. Contr. Insects, Int. Congr. Entomol. , 15th, pp. 97-105 1 85 . Wood, R. J . , Newton, M. E. 1 99 1 . Meiotic drive causing sex ratio distortion in mosquitoes. Am. Nat. 1 37 :379-91 1 85a. Wood, R. J . , Ouda, N. A. 1 987. The genetic basis of resistance and sensitivity to the meiotic drive gene D in the mos quito Aedes aegypti L. Gene/ica 7 1 :6979 1 86 . Wu, C-I. 1983. Virility selection and the in Sex-Ratio Drosophila trait pseudoobscura: I . Sperm displacement and sexual selection. Genetics 105:65152 1 87 . Wu, C-1. 1983. Virility selection and the Sex-Ratio trait in Drosophila pseudoobscura: II. Multiple insemina tion and overall virility selection. Genet ics 105:663-79 1 88. Wu, C-1. 1 983. The fate of autosomal

1 89.

190.

191.

1 92.

1 93 . 194.

557

modifiers of the Sex-ratio trait in Dro sophila and other sex-linked meiotic drive systems. Theor. Populo Bioi. 24: 1 07-20 Wu, C-I. , Beckenbach, A. T. 1 983. Evidence for extensive genetic differen tiation between the Sex-Ratio and the Standard arrangement of Drosophila pseudoobscura and D. persimilis and identification of hybrid sterility factors . Genetics 105:71-86 Wu, C-l . , Hammer, M. F. 1 990. Molecular evolution of ultraselfish genes of meiotic drive systems. In Evolution at the Molecular Level, ed. R. K. Selan der, T. Whittam, A. Clark. Sunderland, MA: Sinauer Wu, C-I. , Lyttle, T. W . , Wu, M-L . , Lin, G-F. 1 988. Association between a satellite DNA sequence and the Respon der of Segregation Distorter in D . melanogaster. Cell 54: 1 79-89 Wu, C-I . , True, J. R . , Johnson, N. 1 989. Fitness reduction associated with the deletion of a satellite DNA array. Nature 34 1 :248-51 Deleted in proof Zweibel, L. J . , Cohn, V. H . , Wright, D . R . , Moore, G . P. 1 982. Evolution of single-copy DNA and the ADH gene in seven Drosophilids. 1. Mol. Evol. 19:62-7 1

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