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Perspectives Copyright 0 1993 by the Genetics Society of America 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 not intended 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 of which 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 affecting female 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, on the 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.
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