Perspectives

Anecdotal, Historical and Critical Commentaries on Genetics Edited by James F. Crow and William F. Dove

Meiosis as an “M” Thing: Twenty-Five Yearsof Meiotic Mutants in Drosophila

R. Scott Hawley Department of Genetics, Universityof Calqornia, Davis, Calqornia 95616

IVE years ago, at the Annual Drosophila Confer- screen for meiotic mutations in flies and it established F ence in New Orleans, talks on Drosophila meiosis the standards by which future mutations would be were squeezed into a session entitled Muscles, Meiosis characterized. In amore general sense, thepaper and Morphogenesis (in other words, meiosis as an “M” represents one of the first heralds of modern genetic thing; hence, the title of this piece). Although that analysis in higher eukaryotes; it reframed the process session represented perhaps the nadir of interest in by which genetics in Drosophila was done. meiotic phenomena by Drosophila workers (there As noted by B. S. BAKER,SANDLER et al. (1968) is were simply too many more interestingslides of zebra- one of the earliest examples of a systematic search for, striped embryos to watch), the field has significantly and study of, mutations affecting a complex regula- regained its momentum in the ensuing years. Papers tory process in higher eukaryotes. To the best of my on meiosis in flies are now common in major journals knowledge, the only precedentsfor this systematic and the number of labs working on meiosis seems to mutational approach in higher eukaryotes were the increase each year. Perhaps now, as the field matures, screens for early embryonic lethals atthe t locus it is worth looking back at thepublication that contin- performed by SALOMEWAELSCH and her colleagues ues to guide work on the genetic analysis of meiosis in the mouse andthe studies of mutations atthe in Drosophila. bithorax complex by ED LEWIS. Thismonth marks the 25th anniversary of the Those notable exceptions aside, much of the prior publication of SANDLER,LINDSLEY, NICOLETTI and work in this century had focused on the analysis of TRIPPA(1 968), the paper thathas served as a corner- mutations encounteredby chance. Moreover,in many stone of the genetic analysis of meiosis in Drosophila cases the focus was centered more on the nature of melanogaster. What follows is an appreciation of that the mutants and the mutational processes themselves paper and also of its intellectual companion, BAKER than on the biological function of the wild-type gene and CARPENTER(1972). It is notintended to be a and the role of genes in regulatory hierarchies. review of the genetic study of meiosis in Drosophila This was certainly true of the genetic analysis of (I have done thatelsewhere: HAWLEY andTHEURKAUF meiosis. Although STURTEVANT, DOBZHANSKY, Nov- 1993 and HAWLEY, MCKIM and ARBEL 1993),but ITSKI, GRELL,SANDLER and LINDSLEYhad certainly rather an attempt to put SANDLERet al. (1968) and conducted detailed studies of the meiotic behavior of BAKERand CARPENTER(1972) into perspective as existing chromosome aberrations,there were very few truly fundamental works. My comments are based on data on mutationsthat affected meiosis in Drosophila. the works themselves, a series of oral histories of Indeed,there were only three recessive mutations varying reliability, and a yellowed copy of DANLIN- known to affect the meiotic process (c(3)G,eand and DSLEY’S application forthe sabbatical fundingthat eq). Although each of these mutations had been stud- supported this study. ied in detail, all of those studies were based on the SANDLERet al. (1968) as a classic paper: In a analysis of single alleles. Moreover, there is no pub- parochial sense, SANDLERet al. (1968)remains the lished evidence of an attempt to determine whether standardfor the mutational analysis of meiosisin or not these mutations were true null alleles. Drosophila; it served as the first report of a direct Certainly there had been no systematic approach to

Genetics 135: 613-618 (November, 1993) 614 R. S. Hawley identify other, perhapsequally important genesin the regation Distorter chromosome was found. meiotic process. To quote from the grant proposal As successful as these screens were, it is reasonable that funded this work, “The existence of these three to ask why SANDLERand LINDSLEYfelt the need to do autosomal recessive mutations that profoundly affect them in Rome (as opposed to their home institutions meiosis, which were encountered purely by chance, in Seattle and San Diego). LINDSLEY’Sgrant applica- encourages one tosuspect that a systematic search for tion presents two justifications for this decision. First, meiotic genes might prove fruitful.” “Ifthe incidence of autosomal recessive lethals in How the screenfor new meiotic mutants was done: North America can be considered general, then south- The mutations were recovered from wild populations ern populationsmight be expected to have more collected in and around Rome at such locales as a mutations than northern ones.” Given that Rome is winery in Salaria and thecity’s wholesale fruit market. well north of San Diego, this rationale only makes LARRYSANDLER claimed for years that thecollections sense if one is already committed to a European sab- were made entirely by DAN LINDSLEY whileLARRY batical. I find more truth in his second justification, conversed with the vintners or the fruit merchants. “As an investigator demonstrates competence in his (Having been LARRY’S student, Ihave no reason to chosen field, the demands forhim to devote his efforts doubt this description of the division of labor). In a to nonresearch efforts become incessant. This is es- story that, until recently, I had always viewed as too pecially true as long as he is at his home institution.” apocryphal to be repeated in print,LARRY also (It might help us to consider the significance of this claimed that while the fruit sellers were initially sus- statement during the next 10 or so committee meet- picious of DAN andhis butterfly net, they were reas- ings.) sured by LARRY’Sclaims, in the vernacular, that this The recovered mutations: As stated above, SAN- was the only therapythat DAN’Sphysicians at the DLER et al. (1968)recovered 15 mutations that af- asylum found effective. DANdid not speak Italian and fected disjunction in one or both sexes. Of these, only was thus fortunately unaware of these conversations. one, mei-S??2, affected disjunction in both sexes; the The decision to searchfor meiotic mutations in remainder affected only females (1 1) or males (3). natural populations was based on theassumption that Two of these mutations, both ofwhich specifically recessive mutations would be found as heterozygotes affect the disjunction of chromosome 4, proved to be in naturalpopulations at afrequency equal to the allelic and to define themei-S8 locus. Of themutations square root of their mutation rate, a frequency high affectingfemale meiosis, the most notable are mei- enoughto be detected in screens. To quotefrom S282 and mei-S51, both of which are described below. LINDSLEY’Sgrant application, “In ordinary ranges of As important as these mutations have subsequently mutation rates this should lead to anincidence of such proven to be, an equal or perhaps even greater yield mutations in nature in excess of that obtainable with was produced by the screen of EMS-treated X chro- most mutagens.” Given that EMS would not be intro- mosomes performed byB. S. BAKERand A. T. C. duced to Drosophila geneticists until 1968, this fre- CARPENTERwho were, at thattime, graduate students quency of mutations seemed greatlyin excess of what in LARRYSANDLER’S laboratory(BAKER and CARPEN- could be obtained with existing mutagens such as 7- TER 1972). This screen of 209 EMS-treated X chro- or X-rays. Moreover,a screen of wild populations mosomes yielded a set of meiotic mutations whose seemed desirablebecause in addition to providing the study has supported muchof the last 20 years of work desired mutations, it would also provide information on meiosis in Drosophila. These include mei-9, mei-41, onthe types and prevalence of such mutations in mei-218, mei-?52 and nod. natural populations. There also appear to have been at least two small The basic scheme was straightforward. Using a 2-3 screens of EMS-treated autosomes in the SANDLER lab, translocation and crossover-suppressing marker chro- one of whichis reported in SANDLER97 (1 1). Although mosomes, lethal-free second and third chromosome thesescreens examined a very limited number of complements would be extracted fromseveral natural chromosomes, 35 in the first instance and 24 in the populations in Italy, and homozygotes for these 2-? second, they yielded a number of very important complements would betested for their effects on mutations, namely c(?)G68, pal, mei-W68 and ord. segregation in both males and females and on recom- These mutations, as well those produced in the two bination in females. Indeed, a significant number of screensdescribed above, were to provideresearch meiotic mutants were recovered; of the 118 2-3 com- materials for generations of students in LARRY’Slab- plements tested in females, 11 significantly increased oratory (cf. BAKER1975; HALL 1972; PARRY 1973). the rate of nondisjunction. Some 123 such 2-3 com- What did these mutations tell us?There was more plements were tested in males, along with 177 half- at issue in this search than simply finding the muta- complements (either 2 or ?), and of these, four had tions. At the time this work was initiated, the existing strong effects on segregation. In addition a new Seg- cytogenetic work had begun to lead to some rather Perspectives 615 specific models of meiotic processes in Drosophila. disjunction of chromosome 4 in males. Similarly, For example, it was widely accepted at that time BAKERand CARPENTER(1972) recovered a large num- that there were two systems for ensuring segregation ber of mutations that affect only the disjunction of in Drosophila females: a chiasmatesystem, and theso- the sex chromosomes. This may define a crucial dif- called distributive system (GRELL1976) that guaran- ference between the two meiotic processes in that, teed the segregation of homologous or heterologous with the quite possibly spurious exception of mei-I, achiasmate chromosomes. According to GRELL,the there are no chromosome-specific meiotic mutations choice of partners in the distributive system was de- in females. termined not by homology, but rather in a manner Most crucially, the analysisof the original set of that was determined by the availability, size and shape mutants recovered in the screen of natural popula- of thesechromosomes. Buried in LINDSLEY’Sgrant tions allowed SANDLERet al. (1 968)to produce a pair proposal, and thus presumably in the intent of the of flow charts, or pathways, describing the deduced authors, is a direct test of that hypothesis. To quote pathway of wild-type functions (see their Figures 3 againfrom the proposal,“If indeed there are two and 4). The descriptions of these pathways are distinct pairing processes that obey different rules, couched in terms, such as landmarks and control points, then there should be different though probably over- which seem to presage more modern discussions of lapping, constellations of genes thatcontrol these the cell cycle.The term landmark was used to describe phenomena.” majorevents in the meiotic cycle, while theterm Indeed, two mutations servingexactly this function, control points was defined by SANDLERet al. (1 968)as nod and mei-SSI, were found in the course of these “points at which a genetic effect is necessary for the initial screens. The mei-S51 mutation was found in the normal process of meiosis to continue.” The analysis screen of natural populationsreported in the SANDLER of the mutants recovered by BAKERand CARPENTER et al. (1968) paper. The nod mutation was found in (1972) allowed these diagrams to be refined to the the parallel screen of EMS-treated chromosomes by point where they becameinvaluable road maps of the BAKERand CARPENTER(1972). Studies of nod would meiotic processes in Drosophila, for example Figure indeed confirm that the process of achiasmate dis- 6 of BAKERand HALL(1 976). junction was truly separate from that which ensured I might, however, point out that Figure 3 was more chiasmate segregation (CARPENTER1973). Moreover, a source of anxiety than pride to LARRY SANDLER. He in a manner not appreciated for almost two decades, opened his issue of GENETICSonly to find that this the study of mei-S5I by L. G. ROBBINSwould provide figure was upside down. Apparently, LARRYwas con- the first evidence that there was not one but rather cerned that someone hadplayed an elaboratepractical two separate processes of achiasmate segregation in joke on him, and checked with his colleague DAVID females (ROBBINS1971 ; HAWLEYet al. 1993). STADLER,whose issue also contained the inverted The work reported in SANDLERet al. (1968) also Figure 3. I am told that LARRYwas eventually calmed revealed that, although the control of meiosis I ap- and reassured by the conviction that the defective pears to be quite different betweenmales and females, copies had only been sent to those individuals whose the processes that ensure sister chromatid adhesion last name started with S. I am happy if LARRYwas and segregation at meiosis I1 appearto be under indeed reassured by that conviction. However, hon- common control in the two sexes. This is exemplified esty requires me to note that the copy on the desk by the mei-S332 mutation, first reportedin this paper, next to me, which belongs to and was sent to M. M. which affects the control of sister chromatid separa- GREEN,also contains an invertedFigure 3, as does the tion in both sexes. A second mutation,ord, which also copy in our library, affects sister chromatid cohesion in both sexes, was Where are the mutants now? In the decade or so recovered in aseparate screen of 24 EMS-treated after their recovery, these mutations provided inves- second chromosomes performed by JIM MASON(1 976) tigators with an incalculable wealth of information. as a graduate studentin LARRYSANDLER’S laboratory. This is perhaps best understood in terms of the use of Work on both mei-S332 and ord was continued by L. these mutations to elucidate both the genetic control S. B. GOLDSTEIN(1980) and the loci are now under of recombination and the mechanism of the process intensive study in the lab of T. ORR-WEAVER(KER- itself. REBROCK et al. 1992; MIYAZAKIand ORR-WEAVER CARPENTERused the existing array of recombina- 1992). tion-defective mutants in genetic studies of both the Finally, the phenotypesof several ofthe male recombination process itself and the mechanisms that meiotic mutations suggested the existence of at least control the number anddistribution of recombinants. some chromosome-specific functionsacting during She also exploited these mutations in the course of male meiosis. Most notably, the two alleles of mei-S8 detailed ultrastructural studies on the formation of recovered by SANDLERet al. (1968) affect only the the synaptonemal complex and analyses of recombi- 616 R. S. Hawley nationnodule structure (CARPENTER1988, 1989). alleles of these genes play in the proper development Finally, her detailed analysis of the effects of several of the fly. recombination-defective mutations on various param- With all of this work in the literature, why did only eters of gene conversion provided crucial insights into four or five labs present at the 1988 meeting in New the underlying mechanism (CARPENTER 1982).Taken Orleans? What happened? Perhaps the loss of appar- together, and in light of data arising from the study ent interest reflected refocusing of major workers in of meiosis in yeast, these studies of recombination- the field toward new problems. Perhaps the field was deficient meiotic mutations in Drosophila served as simply eclipsed by explodingdevelopments in the linchpins in the modern synthesis of the relationship study of various aspects of gene function during em- between chromosomepairing andthe initiation of bryogenesis. Regardless of the cause of that decline, recombination (CARPENTER1987; HAWLEY andAR- the last five years have witnessed a renaissance in the BEL 1993). analysis of meiosis. In addition, the detailedanalysis of the relationships This rebirth has been characterized by three types between exchange and segregation in females homo- of efforts. The first has been the detailed character- zygous forrecombination-defective mutations pro- ization of many of these loci at the genetic level: large vided crucial details for the now commonly accepted searches for additional alleles have been reported for notion that normal levels of exchange are both nec- nod (ZHANG andHAWLEY 1990), mei-S332 (KERRE- essary and sufficient to ensureregular segregation BROCK et al. 1992), ord (MIYAZAKIand ORR-WEAVER (BAKERand HALL 1976; HAWLEY 1988). They also 1992) and mei-218 (K. S. MCKIM and R. S. HAWLEY, provideddata on the mechanisms thatcontrol the unpublished data). Second, the development of con- number and distribution of exchanges, which would focal microscopy has allowed detailed analysis of the normal meiotic process in females, which had previ- have been impossible to glean in the absence of the ously been impossible (THEURKAUFandHAWLEY mutations. More crucially, they also generated impor- 1992). tant insights into the functional significance of those Perhaps the most instructive case of the power of controls: the extraordinary control of chiasma posi- combining the new microscopy with the analysis of a tion probably reflects a compromise between the dif- well characterized meiotic mutation is the analysis of ficulties inherent in resolving proximal chiasmata and the nod mutation. In this case the cytological descrip- the low ability of very distal chiasmata toensure tion of the nod phenotype, together with the finding disjunction. thatthe nod locus encodesa kinesin-like protein These studies of the phenotypes of recombination- (ZHANGet al. 1990), provided truly importantinsights defective mutations were augmented by the finding into the role that the wild-type nod protein plays in that the set of recombination-defective mutations in the process of achiasmate segregation. Drosophila overlapped significantly with the set of But perhapsthe most importantaddition to the mutagen-sensitive or repair-defectivemutations field has been the application of the now traditional (BAKERet al. 1976). Initially this finding generated methods of molecular genetics to the genes defined enormous enthusiasm, bothbecause it linked together by meiotic mutations. As noted above, this process has two emerging new areas in Drosophila genetics and been accomplished for the nod mutation (ZHANGet al. because it seemed to predict that the ongoing bio- 1990)and for the ncd mutation(MCDONALD and chemical studies of repair would provide rapidinsights GOLDSTEIN1990; ENDOW, HENIKOFF and NIEDZIELLA into the nature of the recombinational defects, and 1990). To the best of my knowledge, none of the thusinto thenature of the recombination process genes defined by the mutants recovered by SANDLER itself. Althoughmuch has beenlearned, that later et al. (1968) have so farbeen characterized at the promise remains to be fulfilled. Recent progress on molecular level. However, mei-S332 has been charac- the cloning of such genes (mei-41 and mei-9) by BOYD terized extensively at the cytological level by GOLD- and his collaborators seems likely to providetruly STEIN (1980)and by KERREBROCKet al. (1992).In significant insights into the mechanisms of both re- addition, multiple alleles of this mutation have now combination and repair. been obtained and the molecular analysis should be Finally, in a series of collaborative papers, BRUCE considered as imminent, if indeed it has not been BAKERand MAURIZIOGATTI elegantly demonstrated completed at the time of this writing. A similar set of that many of the recombination-defective or repair- assertions can be made about the ord mutation which, defective strains also exhibit severe defects in mitotic like mei-Sj32, defines a crucial component of sister chromosome behavior (BAKER, CARPENTERand RI- chromatidseparation (MIYAZAKIand ORR-WEAVER POLL 1978; GATTIand BAKER1980). Thiswork again 1992). served to interlock two emerging fields and toprovide This molecular assault on the mutations provided significant new insights into the roles the wild-type by the original screen even extends to reviving the Perspectives 617 dead. Sadly, both alleles of meiS8 were lost shortly BAKER,B. S., A. T. C. CARPENTERand P. RIPOLL,1978 The after the paper was published. I’m aware of at least utilization during mitotic cell cycle of loci controlling meiotic recombination and disjunction in Drosophila melanogaster. Ge- two laboratories seriously looking for new alleles of netics 90 531-578. this locus. Similarly, my own laboratory has become BAKER,B. S., and J. C. HALL,1976 Meiotic mutants: genic control deeply interested in recovering new alleles of mei-T3, of meiotic recombination and chromosome segregation, pp. a semi-sterile line recovered in the original SANDLER 351-434 in Genetics and Biology of Drosophila la, edited by E. et al. (1 968) screen. NOVITSKI and M. ASHBURNER.Academic Press, New York. BAKER,B. S.,J. B. BOYD,A. T. C. CARPENTER,M. M. GREEN,T. Reflections from a cloudy crystal ball:One hopes D. NGUYEN,et al., 1976 Genetic controls of meiotic recom- that the enormous progress in the study of meiosis bination and somatic DNA metabolism in Drosophila melano- observed during thelast five years is predictive of the gaster. Proc. Natl. Acad. Sci. USA 73: 4140-4143. next 25. Curiously, though, my strongest perception CARPENTER,A. T. C., 1973 Amutant defective in distributive of the present is an uneasy feeling that we are running disjunction in Drosophila melanogaster. Genetics 73: 393-428. CARPENTER,A. T. C., 1982 Mismatch repair,gene conversion out of the past. The legacy of meiotic mutants left to and crossing-over in two recombination-defective mutants in us by SANDLERet al. (1968) and by BAKERand CAR- Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 79 5961- PENTER (1972) is nearly exhausted. It is clear that to 5965. take the next few steps in this process, we will once CARPENTER,A. T. C., 1987 Gene conversion, recombination, and again need to perform large screens for meiotic mu- the initiation of meiotic synapsis. BioEssays 6: 232-236. tations in both sexes. My own laboratory, andI suspect CARPENTER,A. T. C., 1988 Thoughts on recombination nodules, meiotic recombination and chiasmata, pp. 526-548 in Genetic those of others as well, has now begun exactly this Recombination, edited byR. KUCHERLAPATIand G. SMITH. task. American Society for Microbiology, Washington, D.C. Perhaps the most significant praise I can place on CARPENTER,A. T. C., 1989 Are there abnormal recombination SANDLERet al. (1968) and onBAKER and CARPENTER nodules in the Drosophila melanogaster meiotic mutant mei-218? (1972) is to note thatthey still serve as the most useful Genome 31: 74-80. guide-posts as we embark in this effort. These more ENDOW,S. A,, S. HENIKoFFand L. s. NIEDZIELLA,1990 Mediation of meiotic and early mitotic chromosome segregation in Dro- modern searches will use higher-tech mutagens (en- sophila by a protein related to kinesin. Nature 345: 81-83. hancer-traps and the like) and they will be combined GATTI,M., S. PIMPINELLIand B. S. BAKER,1980 Relationships with a more molecularly oriented and technically so- between chromatid interchanges, sister chromatid exchanges, phisticated analysis. Unlike SANDLERet ul. (1968) and and meiotic recombination in Drosophilamelanogaster. Proc. BAKERand CARPENTER(1972), our most immediate Natl. Acad. Sci. USA 77: 1575-1 579. goals will be molecular descriptions of the genes in GOLDSTEIN,L. S. B., 1980 Mechanismsof chromosome orienta- tion revealed by two meiotic mutants in Drosophilamelano- question. gaster. Chromosoma (Berl.) 78: 79-1 11. Nonetheless, both the general schemes and the ra- GRELL,R. F., 1976 Distributive pairing, pp. 435-486 in Genetics tionales remain unchanged. We still seek to dissect the and Biology of Drosophila la, edited byE. NOVITSKI and M. meiotic process through the systematic collection and ASHBURNER.Academic Press, New York. analysis of a large number of meiotic mutants. I sus- HALL,J. C., 1972 Chromosome segregation influenced by two alleles of the meiotic mutation c(?)G in Drosophila melanogaster. pect that those of us involved in these mutant hunts Genetics 71: 367-400. secretly hopethat themutants recovered in our HAWLEY,R. S., 1988 Exchange and chromosome segregation in screens will prove as valuable in the next 25 years as eukaryotes, pp. 497-525 in Genetic Recombination, edited by R. did those of our predecessors in the last 25 years. KUCHERLAPATIand G. SMITH.American Society for Microbi- ology, Washington, D.C. 1 wish to thank BRUCEBAKER, ADELAIDE CARPENTER, JIM MASON HAWLEY,R. S., and T. ARBEL, 1993 Yeast genetics and the fall and especially DANLINDSLEY for sharing their memories and in- of the classical view of meiosis. Cell72: 301-303. sights. I also thank DEANPARKER, from whose reprint collection I HAWLEY,R. S., K. S. MCKIM and T. ARBEL,1993 Meiotic segre- unearthed the sabbatical grant application written by DAN LIN- gation in Drosophilamelanogaster females: molecules, mecha- DSLEY. Finally, I want to thank ADELAIDECARPENTER, BRUCE nisms, and myths. Annu. Rev. Genet. 27: 281-317. BAKER,KENNETH BURTIS,BARRY GANETZKY, JENNIFER FRAZIER HAWLEY,R. S., and W. E. THEURKAUF,1993 Requiem forthe and KIM MCKIM for their valuable comments on the manuscript. distributive system: achiasmate segregation in Drosophila fe- Due to space limitations I have had to omit references to many of males. Trends Genet. 9: 3 10-3 16. the studies done by various students in the SANDLER laboratoryand HAWLEY,R. S., H. IRICK,A. E. ZITRON, D. A. HADDOX,A. LOHE, by other workers. I deeply regret this limitation. This paper is et al., 1993 There are two mechanisms of achiasmate segre- dedicated tothe memory of LARRYSANDLER, whose presence gation in Drosophila, one of which requires heterochromatic remains undiminished. homology. Dev. Genet. 13: 440-467. KERREBROCK,A. W., W. Y. MIYAZAKI,D. BIRNBYand T. L. ORR- LITERATURECITED WEAVER,1992 The Drosophila meiS332 gene promotes sis- BAKER,B. S., 1975 Paternal loss (pal): a meiotic mutant in Dm- ter-chromatid adhesion in meiosis followingkinetochore differ- sophilamelanogaster causing loss of paternal chromosomes. entiation. Genetics 130 827-841. Genetics 80267-296. MASON,J. M., 1976 Orientationdisrupter (ord): a recombination- BAKER,B. S., and A. T. C. CARPENTER,1972 Genetic analysis of defective and disjunction-defective meiotic mutant in Drosoph- sex chromosome meiotic mutants in Drosophilamelanogaster. ila melanagaster. Genetics 84 545-572. Genetics 71: 255-286. MCDONALD,H. B., and L. S. B. GOLDSTEIN, 1990 Identification 618 R. S. Hawley

and characterization of a gene encoding akinesin-like protein SANDLER,L. M., D. L. LINDSLEY,B. NICOLETTI and G. TRIPPA, in Drosophila. Cell 61: 991-1000. 1968 Mutants affecting meiosis in natural populations of Dro- MIYAZAKI,W. Y., and T. L. ORR-WEAVER, 1992Sister chromatid sophila melanoguster. Genetics 60 525-558. misbehavior in Drosophila ord mutants. Genetics 132: 1047- THEURKAUF,W. E., and R. S. HAWLEY,1992 Meiotic spindle 1061. assembly inDrosophila females: behavior of nonexchange chromosomes and the effects of mutations in the nod kinesin-like PARRY,D. M., 1973 A meiotic mutant affecting recombination in protein. J. Cell Biol. 116: 1167-1 180. female Drosophila melanoguster. Genetics 465-486. 73: ZHANG,P., and R. S. HAWLEY,1990 The genetic analysisof ROBBINS,L. G., 197 1 Nonexchange alignment: a meiotic process distributive segregation in Drosophila melanoguster. 11. Further revealed by a synthetic meiotic mutant of Drosophila melano- genetic analysis of the nod locus. Genetics 125: 115-127. gaster. Mol. Gen. Genet. 110: 144-166. ZHANG, P., B. A. KNOWLES, L.S. B. COLDSTEIN and R. S. HAWLEY, SANDLER,L. M., 1971 Induction of autosomal meiotic mutants by 1990 A kinesin-like proteinrequired for distributive chro- EMS in Drosophila melanogaster. Genetics 39: 365-377. mosome segregation in Drosophila. Cell 62: 1053-1062.