Spore killer, a chromosomal factor in neurospora that kills meiotic products not containing it

Three chromosomal factors called Spore killer (Sk) have been found in wild populations of Neurospora sitophila and N. intermedia. Sk resembles other examples of meiotic drive such as Segregation Distorter in Drosophila, Pollen killer in wheat, and Gamete eliminator in tomato. In crosses heterozygous for Sk, each ascus contains four viable black ascospores and four inviable, undersize, clear ascospores, with second-division segregations infrequent. The survivors contain the killer allele Sk^K, while unlinked markers segregate normally. Reciprocal crosses are identical. When crosses are homozygous for an allele of Sk, all eight ascospores are viable and black in most asci. (Many homozygous crosses have a background level of randomly occurring inviable spores; however, the pattern of 4 viable: 4 small clear ascospores is not found in any of the asci of Sk-homozygous crosses.)——Killer (Sk-1^K) and sensitive (Sk-1^S) alleles occur in about equal numbers among a worldwide sample of N. sitophila strains, following no geographic pattern. No killer allele has been found in N. crassa. Sk-2^K and Sk-3^K, found in N. intermedia, are rare. Most N. intermedia strains are Sk-2^S and Sk-3^S, but some are wholly or partially resistant to one or both of the killer alleles, while not themselves acting as killers. Sk-2^K and Sk-2^R are both specific in conferring resistance to Sk-2^K, but not to Sk-3^K. Likewise Sk-3^K and Sk-3^R are resistant specifically to Sk-3^K, but not to Sk-2^K. Resistance segregates as an allele of Sk^K.——Sk-2 and Sk-3 have been mapped near the centromere of linkage group III after introgression into N. crassa, where crossing over is normally 11% between the proximal III markers acr-2 and leu-1. But crossing over is absent in this region when either of the killer alleles is heterozygous (Sk-2^K x Sk-2^S, Sk-3^K x Sk-3^S and Sk-2^K x Sk-2^R have been examined).     

Meiotic drive in fungi: Chromosomal elements that cause fratricide and distort genetic ratios

Fungal Spore killers (Sk), studied most extensively inNeurospora and to a lesser extent inPodospora, Gibberella andCochliobolus, cause the death of ascospores (= meiospores) that do not contain the killer (Skk) element. When a Spore killer is heterozygous (SkK× Sks) inNeurospora, every ascus (= meiocyte) contains four normal-sized, black, viable ascospores (SkK), and four ascospores that are tiny, unpigmented and unviable (SKs). Killing of sensitive nuclei is expressed postmeiotically, and results in gross distortion of segregation ratios forSk-linked genes. A sensitive nucleus that would otherwise die is rescued if a killer nucleus is also enclosed in the same ascospore. InNeurospora, Sk is centromere-linked (linkage group III), and when heterozygous, shows a recombination block in a 30-map-unit region spanning the centromere of linkage group III. There is no ascospore death or recombination block in killer×killer or sensitive×sensitive crosses. Spore killers are fairly common inGibberella fujikuroi andNeurospora sitophila but extremely rare inN. intermedia, and have not yet been found among natural isolates ofN. crassa.     

Cytogenetic behavior of spore killer genes in neurospora

Crosses heterozygous and homozygous for Sk-1, Sk-2 and Sk-3 were examined by light microscopy. All three Spore killers behave similarly. In heterozygous killer x sensitive crosses, meiosis and ascospore development are normal until after the second postmeiotic mitosis when four of the eight ascospores in each ascus stop developing and degenerate. The four surviving ascospores carry the killer. Death of sensitives thus occurs only after killer and sensitive alleles, Sk^K and Sk^S, have segregated into separate ascospores. Homozygous killer x killer crosses do not show such a pattern of degeneration. Either all ascospores are normal or, if some fail to mature, they do not resemble the degenerating sensitive ascospores in heterozygous asci.——With Sk-2, it was shown that Sk^S nuclei do not abort when both Sk^K and Sk^S are present in the same ascospore. Mutants affecting ascus development were used to obtain large ascospores enclosing both Sk^K and Sk^S meiotic products in a common cytoplasm. Sk^S nuclei do not then undergo the degeneration that would be seen if they were sequestered into separate ascospores, and viable Sk^S progeny are recovered in undiminished numbers when the mixed multinucleate large ascospores are germinated. In a four-spored mutant, where each ascospore encloses a single nucleus following meiosis, degeneration of Sk^S ascospores nevertheless occurs, even though the third nuclear division is omitted. Cycloheximide and temperature treatments do not affect the expression of Sk^K.     

Recombination block in the Spore killer region of Neurospora

Spore killers Sk-2K and Sk-3K are chromosomal meiotic drive factors in Neurospora. In heterozygous crosses, ascospores not containing the Spore killer die. Sk-2K and Sk-3K, which differ in killing specificity, were found to be associated with suppression of recombination in a centromere-spanning region of linkage group III, and investigation of that recombination block is reported here. The block covers a region that is normally 30 to 40 map units long. A locus (r(Sk-2)) conferring resistance to Sk-2K maps to the left end of the recombination block. Recombination is normal in r(Sk-2) X Sk sensitive but blocked in Sk-2K X r(Sk-2); so the block does not depend upon killing. By selective plating, SkK stocks carrying genetic markers within the block were obtained at frequencies on the order of 10(-5) or 10(-6). Since this tight block is far beyond what has been observed for genetic reduction of recombination, a structural basis is assumed. No evidence of chromosome rearrangement was obtained. Crosses homozygous for Sk-2K show normal crossing-over and map order for the flanking markers cum and his-7 and three included markers (acr-7, acr-2, and leu-1). Results would be consistent with a divergence of sequence great enough to interfere with homologous pairing.     

Neurospora spore killers Sk-2 and Sk-3 suppress meiotic silencing by unpaired DNA

In Neurospora crassa, pairing of homologous DNA segments is monitored during meiotic prophase I. Any genes not paired with a homolog, as well as any paired homologs of that gene, are silenced during the sexual phase by a mechanism known as meiotic silencing by unpaired DNA (MSUD). Two genes required for MSUD have been described previously: sad-1 (suppressor of ascus dominance), encoding an RNA-directed RNA polymerase, and sad-2, encoding a protein that controls the perinuclear localization of SAD-1. Inactivation of either sad-1 or sad-2 suppresses MSUD. We have now shown that MSUD is also suppressed by either of two Spore killer strains, Sk-2 and Sk-3. These were both known to contain a haplotype segment that behaves as a meiotic drive element in heterozygous crosses of killer x sensitive. Progeny ascospores not carrying the killer element fail to mature and are inviable. Crosses homozygous for either of the killer haplotypes suppress MSUD even though ascospores are not killed. The killer activity maps to the same 30-unit-long region within which recombination is suppressed in killer x sensitive crosses. We suggest that the region contains a suppressor of MSUD.     

Reproductive isolation in a nascent species pair is associated with aneuploidy in hybrid offspring

Speciation may occur when the genomes of two populations accumulate genetic incompatibilities and/or chromosomal rearrangements that prevent inter-breeding in nature. Chromosome stability is critical for survival and faithful transmission of the genome, and hybridization can compromise this. However, the role of chromosomal stability on hybrid incompatibilities has rarely been tested in recently diverged populations. Here, we test for chromosomal instability in hybrids between nascent species, the ‘dwarf’ and ‘normal’ lake whitefish (Coregonus clupeaformis). We examined chromosomes in pure embryos, and healthy and malformed backcross embryos. While pure individuals displayed chromosome numbers corresponding to the expected diploid number (2n = 80), healthy backcrosses showed evidence of mitotic instability through an increased variance of chromosome numbers within an individual. In malformed backcrosses, extensive aneuploidy corresponding to multiples of the haploid number (1n = 40, 2n = 80, 3n = 120) was found, suggesting meiotic breakdown in their F₁ parent. However, no detectable chromosome rearrangements between parental forms were identified. Genomic instability through aneuploidy thus appears to contribute to reproductive isolation between dwarf and normal lake whitefish, despite their very recent divergence (approx. 15–20 000 generations). Our data suggest that genetic incompatibilities may accumulate early during speciation and limit hybridization between nascent species.     

Extensive Divergence Between Mating-Type Chromosomes of the Anther-Smut Fungus

Genomic regions that determine mating compatibility are subject to distinct evolutionary forces that can lead to a cessation of meiotic recombination and the accumulation of structural changes between members of the homologous chromosome pair. The relatively recent discovery of dimorphic mating-type chromosomes in fungi can aid the understanding of sex chromosome evolution that is common to dioecious plants and animals. For the anther-smut fungus, Microbotryum lychnidis-dioicae (= M. violaceum isolated from Silene latifolia), the extent of recombination cessation on the dimorphic mating-type chromosomes has been conflictingly reported. Comparison of restriction digest optical maps for the two mating-type chromosomes shows that divergence extends over 90% of the chromosome lengths, flanked at either end by two pseudoautosomal regions. Evidence to support the expansion of recombination cessation in stages from the mating-type locus toward the pseudoautosomal regions was not found, but evidence of such expansion could be obscured by ongoing processes that affect genome structure. This study encourages the comparison of forces that may drive large-scale recombination suppression in fungi and other eukaryotes characterized by dimorphic chromosome pairs associated with sexual life cycles.     

Analysis of two additional loci in Neurospora crassa related to Spore killer-2

Two new loci found in one strain of Neurospora crassa (P2604) collected in Malaya are related to the meiotic drive system Spore killer Sk-2. Sk-2 was found in Neurospora intermedia and introgressed into N. crassa. P2604 showed high resistance to killing when crossed to Sk-2. This resistance was found to be linked to, but not allelic to, resistance locus r(Sk-2) on LGIIIL. Analysis showed that the high resistance phenotype of P2604 requires resistance alleles at two different loci on LGIIIR. Strains carrying a resistance allele at only the proximal or the distal locus, respectively, were obtained and intercrossed. Highly resistant strains were obtained by rejoining the two genes. The proximal locus alone confers a low level of resistance. This locus was named pr(Sk-2) for partial resistance to Sk-2. The distal locus was named mod(pr) because its only known phenotype is to modify pr(Sk-2).     

Geographic distribution of neurospora spore killer strains and strains resistant to killing

Spore killer strains, found in Neurospora, provided the first recognized example of meiotic drive in fungi. In the present study, natural populations throughout the world were examined for the presence of killer strains and strains that are resistant to killing. In N. intermedia, Sk-2 and Sk-3 are present but are rare. Killer strains were found at only five sites, in Borneo, Java, and Papua New Guinea. Nonkiller strains that are resistant to killing by Sk-2 or Sk-3 are frequent in that part of the world where the killer strains are present, but resistant stains were not found in regions where killers are absent. In N. sitophila, Sk-1 killer strains are common in nature, but only 1 of 392 nonkiller strains was resistant. In N. crassa, no killer strain was found among >500, but widely scattered Sk-2-resistant strains were present, suggesting the past or present existence of killers.     

Evidence for dominant suppression of repeat-induced point mutation (RIP) in crosses with the wild-isolatedNeurospora crassa strains Sugartown and Adiopodoume-7

A convenient assay to score repeat-induced point mutation (RIP) inNeurospora employs theerg-3 locus as a mutagenesis target. Using this assay we screened 132 wild-isolatedNeurospora crassa strains for ability to dominantly suppress RIP. RIP was exceptionally inefficient in crosses with the wild isolates Sugartown (P0854) and Adiopodoume-7 (P4305), thereby suggesting the presence of dominant RIP suppressors in these strains. In other experiments, we found no evidence for dominant RIP suppression by theSpore killer haplotypesSk-2 andSk-3.     

Genetic recombination variation in wild Robertsonian mice: on the role of chromosomal fusions and Prdm9 allelic background

Despite the existence of formal models to explain how chromosomal rearrangements can be fixed in a population in the presence of gene flow, few empirical data are available regarding the mechanisms by which genome shuffling contributes to speciation, especially in mammals. In order to shed light on this intriguing evolutionary process, here we present a detailed empirical study that shows how Robertsonian (Rb) fusions alter the chromosomal distribution of recombination events during the formation of the germline in a Rb system of the western house mouse (Mus musculus domesticus). Our results indicate that both the total number of meiotic crossovers and the chromosomal distribution of recombination events are reduced in mice with Rb fusions and that this can be related to alterations in epigenetic signatures for heterochromatinization. Furthermore, we detected novel house mouse Prdm9 allelic variants in the Rb system. Remarkably, mean recombination rates were positively correlated with a decrease in the number of ZnF domains in the Prdm9 gene. The suggestion that recombination can be modulated by both chromosomal reorganizations and genetic determinants that control the formation of double-stranded breaks during meiosis opens new avenues for understanding the role of recombination in chromosomal speciation.     

The Utilization during Mitotic Cell Division of Loci Controlling Meiotic Recombination and Disjunction in DROSOPHILA MELANOGASTER

To inquire whether the loci identified by recombination-defective and disjunction-defective meiotic mutants in Drosophila are also utilized during mitotic cell division, the effects of 18 meiotic mutants (representing 13 loci) on mitotic chromosome stability have been examined genetically. To do this, meiotic-mutant-bearing flies heterozygous for recessive somatic cell markers were examined for the frequencies and types of spontaneous clones expressing the cell markers. In such flies, marked clones can arise via mitotic recombination, mutation, chromosome breakage, nondisjunction or chromosome loss, and clones from these different origins can be distinguished. In addition, meiotic mutants at nine loci have been examined for their effects on sensitivity to killing by UV and X rays.—Mutants at six of the seven recombination-defective loci examined (mei-9, mei-41, c(3)G, mei-W68, mei-S282, mei-352, mei-218) cause mitotic chromosome instability in both sexes, whereas mutants at one locus (mei-218) do not affect mitotic chromosome stability. Thus many of the loci utilized during meiotic recombination also function in the chromosomal economy of mitotic cells.—The chromosome instability produced by mei-41 alleles is the consequence of chromosome breakage, that of mei-9 alleles is primarily due to chromosome breakage and, to a lesser extent, to an elevated frequency of mitotic recombination, whereas no predominant mechanism responsible for the instability caused by c(3)G alleles is discernible. Since these three loci are defective in their responses to mutagen damage, their effects on chromosome stability in nonmutagenized cells are interpreted as resulting from an inability to repair spontaneous lesions. Both mei-W68 and mei-S282 increase mitotic recombination (and in mei-W68, to a lesser extent, chromosome loss) in the abdomen but not the wing. In the abdomen, the primary effect on chromosome stability occurs during the larval period when the abdominal histoblasts are in a nondividing (G2) state.—Mitotic recombination is at or above control levels in the presence of each of the recombination-defective meiotic mutants examined, suggesting that meiotic and mitotic recombination are under separate genetic control in Drosophila.—Of the six mutants examined that are defective in processes required for regular meiotic chromosome segregation, four (l(1)TW-6^cs, ca^nd, mei-S332, ord) affect mitotic chromosome behavior. At semi-restrictive temperatures, the cold sensitive lethal l(1)TW-6^cs causes very frequent somatic spots, a substantial proportion of which are attributable to nondisjunction or loss. Thus, this locus specifies a function essential for chromosome segregation at mitosis as well as at the first meiotic division in females. The patterns of mitotic effects caused by ca^nd, mei-S332, and ord suggest that they may be leaky alleles at essential loci that specify functions common to meiosis and mitosis. Mutants at the two remaining loci (nod, pal) do not affect mitotic chromosome stability.     

Sex-Ratio Meiotic Drive and Y-Linked Resistance in Drosophila affinis

Genetic elements that cheat Mendelian segregation by biasing transmission in their favor gain a significant fitness benefit. Several examples of sex-ratio meiotic drive, where one sex chromosome biases its own transmission at the cost of the opposite sex chromosome, exist in animals and plants. While the distorting sex chromosome gains a significant advantage by biasing sex ratio, the autosomes, and especially the opposite sex chromosome, experience strong selection to resist this transmission bias. In most well-studied sex-ratio meiotic drive systems, autosomal and/or Y-linked resistance has been identified. We specifically surveyed for Y-linked resistance to sex-ratio meiotic drive in Drosophila affinis by scoring the sex ratio of offspring sired by males with a driving X and one of several Y chromosomes. Two distinct types of resistance were identified: a restoration to 50/50 sex ratios and a complete reversal of sex ratio to all sons. We confirmed that fathers siring all sons lacked a Y chromosome, consistent with previously published work. Considerable variation in Y-chromosome morphology exists in D. affinis, but we showed that morphology does not appear to be associated with resistance to sex-ratio meiotic drive. We then used two X chromosomes (driving and standard) and three Y chromosomes (susceptible, resistant, and lacking) to examine fertility effects of all possible combinations. We find that both the driving X and resistant and lacking Y have significant fertility defects manifested in microscopic examination of testes and a 48-hr sperm depletion assay. Maintenance of variation in this sex-ratio meiotic drive system, including both the X-linked distorter and the Y-resistant effects, appear to be mediated by a complex interaction between fertility fitness and transmission dynamics.     

Meiotic mutations from natural populations ofDrosophila melanogaster

Two meiotic genes from natural populations are described. A female meiotic mutation,mei(1)g13, mapped to 17.4 on the X chromosome, causes nondisjunction of all homologs except for the fourth chromosomes. In addition, it reduces recombination by 10% in the homozygotes and causes 18% increased recombination in the heterozygotes. A male meiotic mutation,mei-1223 ^m144 , is located on the third chromosome. Although this mutation causes nondisjunction of all chromosomes, each chromosome pair exhibits a different nondisjunction frequency. Large variations in the sizes of the premature sperm heads observed in the homozygotes may reflect irregular meiotic pairing and the subsequent abnormal segregation, resulting in aneuploid chromosome complements.     

Fungal chromosomes

There are now four well-established methods to examine the chromosomes of filamentous fungi: mapping genes to linkage groups by recombination analyses, light-microscopic observation of chromosomes in meiotic divisions, electron-microscopic observation of the synaptonemal complexes between homologous chromosomes in prophase of meiosis, and separation of chromosomes as individual bands by pulsed field gel electrophoresis. These techniques and their contributions are described in brief with special reference toNeurospora. A fifth technique will be used more and more in characterizing chromosomes at the molecular level as DNA sequencing is completed for a limited number of the fungi. However, only the molecular studies of chromosome structures as they relate to centromeres, telomeres or nucleolus organizer regions are discussed, as is the potential usefulness of DNA sequencing to identify the junctions of chromosome rearrangements.     

Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse

Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm) and Mus m. domesticus (Mmd), it further functions as the major hybrid sterility gene. In the latter role Prdm9 interacts with the hybrid sterility X 2 (Hstx2) genomic locus on Chromosome X (Chr X) by a still unknown mechanism. Here we investigated the meiotic recombination rate at the genome-wide level and its possible relation to hybrid sterility. Using immunofluorescence microscopy we quantified the foci of MLH1 DNA mismatch repair protein, the cytological counterparts of reciprocal crossovers, in a panel of inter-subspecific chromosome substitution strains. Two autosomes, Chr 7 and Chr 11, significantly modified the meiotic recombination rate, yet the strongest modifier, designated meiotic recombination 1, Meir1, emerged in the 4.7 Mb Hstx2 genomic locus on Chr X. The male-limited transgressive effect of Meir1 on recombination rate parallels the male-limited transgressive role of Hstx2 in hybrid male sterility. Thus, both genetic factors, the Prdm9 gene and the Hstx2/Meir1 genomic locus, indicate a link between meiotic recombination and hybrid sterility. A strong female-specific modifier of meiotic recombination rate with the effect opposite to Meir1 was localized on Chr X, distally to Meir1. Mapping Meir1 to a narrow candidate interval on Chr X is an important first step towards positional cloning of the respective gene(s) responsible for variation in the global recombination rate between closely related mouse subspecies.     

Step-by-step evolution of neo-sex chromosomes in geographical populations of wild silkmoths,Samia cynthia ssp.

Geographical subspecies of wild silkmoths, Samia cynthia ssp. (Lepidoptera: Saturniidae), differ considerably in sex chromosome constitution owing to sex chromosome fusions with autosomes, which leads to variation in chromosome numbers. We cloned S. cynthia orthologues of 16 Bombyx mori genes and mapped them to chromosome spreads of S. cynthia subspecies by fluorescence in situ hybridization (FISH) to determine the origin of S. cynthia neo-sex chromosomes. FISH mapping revealed that the Z chromosome and chromosome 12 of B. mori correspond to the Z chromosome and an autosome (A₁) of S. c. ricini (Vietnam population, 2n=27, Z0 in female moths), respectively. B. mori chromosome 11 corresponds partly to another autosome (A₂) and partly to a chromosome carrying nucleolar organizer region (NOR) of this subspecies. The NOR chromosome of S. c. ricini is also partly homologous to B. mori chromosome 24. Furthermore, our results revealed that two A₁ homologues each fused with the W and Z chromosomes in a common ancestor of both Japanese subspecies S. c. walkeri (Sapporo population, 2n=26, neo-Wneo-Z) and S. cynthia subsp. indet. (Nagano population, 2n=25, neo-WZ₁Z₂). One homologue, corresponding to the A₂ autosome in S. c. ricini and S. c. walkeri, fused with the W chromosome in S. cynthia subsp. indet. Consequently, the other homologue became a Z₂ chromosome. These results clearly showed a step-by-step evolution of the neo-sex chromosomes by repeated autosome–sex chromosome fusions. We suggest that the rearrangements of sex chromosomes may facilitate divergence of S. cynthia subspecies towards speciation.     

Experimental Population Genetics of Meiotic Drive Systems I. Pseudo-Y Chromosomal Drive as a Means of Eliminating Cage Populations of DROSOPHILA MELANOGASTER

The experimental population genetics of Y-chromosome drive in Drosophila melanogaster is approximated by studying the behavior of T(Y;2),SD lines. These exhibit "pseudo-Y" drive through the effective coupling of the Y chromosome to the second chromosome meiotic drive locus, Segregation distorter (SD). T(Y;2),SD males consequently produce only male offspring. When such lines are allowed to compete against structurally normal SD⁺ flies in population cages, T(Y;2),SD males increase in frequency according to the dynamics of a simple haploid selection model until the cage population is eliminated as a result of a deficiency in the number of adult females. Cage population extinction generally occurs within about seven generations.—Several conclusions can be drawn from these competition cage studies:

(1) Fitness estimates for the T(Y;2),SD lines (relative to SD⁺ ) are generally in the range of 2–4, and these values are corroborated by independent estimates derived from studies of migration-selection equilibrium.

(2) Fitness estimates are unaffected by cage replication, sample time, or the starting frequency of T(Y;2),SD males, indicating that data from diverse cages can be legitimately pooled to give an overall fitness estimate.

(3) Partitioning of the T(Y;2),SD fitnesses into components of viability, fertility, and frequency of alternate segregation (Y + SD from X + SD⁺) suggests that most of the T(Y;2),SD advantage derives from the latter two components. Improvements in the system might involve increasing both the viability and the alternate segregation to increase the total fitness.

While pseudo-Y drive operates quite effectively against laboratory stocks, it is less successful in eliminating wild-type populations which are already segregating for suppressors of SD action. This observation suggests that further studies into the origin and rate of accumulation of suppressors of meiotic drive are needed before an overall assessment can be made of the potential of Y-chromosome drive as a tool for population control.

     

X-4 Translocations and Meiotic Drive in Drosophila melanogaster Males: Role of Sex Chromosome Pairing

Males carrying certain X-4 translocations exhibit strongly skewed sperm recovery ratios. The X^P4^D half of the translocation disjoins regularly from the Y chromosome and the 4^PX^D half disjoins regularly from the normal 4. Yet the smaller member of each bivalent is recovered in excess of its pairing partner, apparently due to differential gametic lethality. Chromosome recovery probabilities are multiplicative; the viability of each genotype is the product of the recovery probability of its component chromosomes. Meiotic drive can also be caused by deficiency for X heterochromatin. In(1)sc^4Lsc^8R males show the same size dependent chromosome recoveries and multiplicative recovery probabilities found in T(1;4)B^S males. Meiotic drive in In(1)sc^4Lsc^8R males has been shown to be due to X-Y pairing failure. Although pairing is regular in the T(X;4) males, the striking phenotypic parallels suggest a common explanation. The experiments described below show that the two phenomena are, in fact, one and the same. X-4 translocations are shown to have the same effect on recovery of independently assorting chromosomes as does In(1)sc^4Lsc^8R. Addition of pairing sites to the 4^PX^D half of the translocation eliminates drive. A common explanation—failure of the distal euchromatic portion of the X chromosome to participate in X:Y meiotic pairing—is suggested as the cause for drive. The effect of X chromosome breakpoint on X-4 translocation induced meiotic drive is investigated. It is found that translocations with breakpoints distal to 13C on the salivary map do not cause drive while translocations broken proximal to 13C cause drive. The level of drive is related to the position of the breakpoint—the more proximal the breakpoint the greater the drive.