Showing papers in "Genetics in 1974"

The genetics of caenorhabditis elegans

Abstract: Methods are described for the isolation, complementation and mapping of mutants of Caenorhabditis elegans, a small free-living nematode worm. About 300 EMS-induced mutants affecting behavior and morphology have been characterized and about one hundred genes have been defined. Mutations in 77 of these alter the movement of the animal. Estimates of the induced mutation frequency of both the visible mutants and X chromosome lethals suggests that, just as in Drosophila, the genetic units in C. elegans are large.

The evolutionary advantage of recombination

Abstract: The controversy over the evolutionary advantage of recombination initially discovered by Fisher and by Muller is reviewed. Those authors whose models had finite-population effects found an advantage of recombination, and those whose models had infinite populations found none. The advantage of recombination is that it breaks down random linkage disequilibrium generated by genetic drift. Hill and Robertson found that the average effect of this randomly-generated linkage disequilibrium was to cause linked loci to interfere with each other's response to selection, even where there was no gene interaction between the loci. This effect is shown to be identical to the original argument of Fisher and Muller. It also predicts the "ratchet mechanism" discovered by Muller, who pointed out that deleterious mutants would more readily increase in a population without recombination. Computer simulations of substitution of favorable mutants and of the long-term increase of deleterious mutants verified the essential correctness of the original Fisher-Muller argument and the reality of the Muller ratchet mechanism. It is argued that these constitute an intrinsic advantage of recombination capable of accounting for its persistence in the face of selection for tighter linkage between interacting polymorphisms, and possibly capable of accounting for its origin.

Sampling variances of heterozygosity and genetic distance

Abstract: Mathematical formulae for the sampling variances of average heterozygosity and Nei's genetic distance are developed. These sampling variances are decomposed into their two components, i.e. the inter-locus and intra-locus variances. The relationship between the number of loci and the number of individuals per locus to be examined for estimating average heterozygosity and genetic distance is also discussed. The utility of the inter-locus variance of heterozygosity for studying the mechanism of maintenance of genetic variability in populations is indicated.

The dna of caenorhabditis elegans

Abstract: Chemical analysis and a study of renaturation kinetics show that the nematode, Caenorhabditis elegans, has a haploid DNA content of 8 x 10(7) base pairs (20 times the genome of E. coli). Eighty-three percent of the DNA sequences are unique. The mean base composition is 36% GC; a small component, containing the rRNA cistrons, has a base composition of 51% GC. The haploid genome contains about 300 genes for 4S RNA, 110 for 5S RNA, and 55 for (18 + 28)S RNA.

Natural selection for within-generation variance in offspring number

Abstract: In this paper it is shown that natural selection can act on the within-generation variance in offspring number. The fitness of a genotype will increase as its variance in offspring number decreases. The intensity of selection on the variance component is inversely proportional to population size, although the fixation probability of a gene which differs from its allele only in the variance in its offspring number is independent of population size. The concept of effective population size is shown to be of limited use when there is genetic variation in the variance in offspring number.

Genetic conservation: our evolutionary responsibility

Abstract: The conservation of the crop varieties of traditional agriculture in the centers of genetic diversity is essential to provide genetic resources for plant improvement. These resources are acutely threatened by rapid agricultural development which is essential for the welfare of millions. Methodologies for genetic conservation have been worked out which are both effective and economical. Urgent action is needed to collect and preserve irreplaceable genetic resources. Wild species, increasingly endangered by loss of habitats, will depend on organized protection for their survival. On a long term basis this is feasible only within natural communities in a state of continuing evolution, hence there is an urgent need for exploration and clarification of the genetic principles of conservation. Gene pools of wild species are increasingly needed for various uses, from old and new industries to recreation. But the possibility of a virtual end to the evolution of species of no direct use to man raises questions of responsibility and ethics.

A general model to account for enzyme variation in natural populations

Abstract: Approximate conditions for genetic polymorphism in temporally and spatially varying environments are presented for loci which are intermediate at the level of fitness or at the level of gene function. The conditions suggest that polymorphism will be more likely in more variable environments while unlikely in constant environments. Biochemical evidence is presented to justify the assumption of heterozygote intermediacy. Observations on natural populations are cited which substantiate the claim that allozymic polymorphism is primarily due to selection acting on environmental variation in gene function.

Mitochondrial genetics IX: A model for recombination and segregation of mitochondrial genomes in saccharomyces cerevisiae.

Abstract: HE last few years have witnessed the accumulation of a considerable body experimental data dealing with the isolation of mitochondrial mutants in yeast conferring resistance to various inhibitors and with the results of two, three or four factor crosses using these mutants as genetic markers. All these results can be classified as belonging to two types of experimental approaches: one based essentially on an analysis of the progeny of an individual cell heterozygous for mitochondrial genetic markers and the second based essentially on an analysis of the progeny of a population of cells heterozygous for mitochondrial genetic markers. The first approach is exemplified by the work of LINNANE et al. 1968; THOMAS and WILKIE 1968; COEN et al. 1970; SAUNDERS et al. 1971 ; LUKINS et al. 1973; WILKIE and THOMAS 1973; the second by that of COEN et al. 1970; BOLOTIN et al. 1971; KLEESE, GROTBECK and SNYDER 1972 a and b; RANK and BECHHANSEN 1972; AVNER et al. 1973; AVNER and GRIFFITHS 1973; HOWELL et al. 1973; RANK 1973; WAKABAYASHI and KAMEI 1973; WOLF, DUJON and SLONIMSKI 1973; NETTER et al. 1974; COEN et al. (in preparation). At the very start of this period of mitochondrial genetics it became apparent that individual zygotic clones issued from a cross of two mitochondrially pure lines may behave quite differently from one another with respect to the types and proportions of the mitochondrial genotypes they give rise to (COEN et al. 1970). Pedigree analyses performed since have shown that not only are the proportions of different cell types variable from clone to clone but also their order of appearance (LUKINS et al. 1973; WILKIE 1973). Apart from the demonstration of interand intraclonal heterogeneity as one of the basic features of mitochondrial crosses, reminiscent of course of the heterogeneity in burst size and composition in bacteriophages crosses, this “individualistic” approach has not as yet yielded any substantial insights into the mechanism of mitochondrial genetics. The “population” approach is based on what COEN et al. (1970) have called a standard cross and has been adopted with no or only minor modifications by several authors (BOLOTIN et al. 1971; KLEESE, GROTBECK and SNYDER 1972 a and b; RANK and BECH-HANSEN 1972; SUDA and UCHIDA 1972; AVNER and GRIFFITHS 1973; AVNER et al. 1973; HOWELL et al. 1973; RANK 1973; TREMBATH et al. 1973; WAKABAYASHI and KAMEI 1973; WOLF, DUJON and SLONIMSKI 1973; NETTER et al. 1974 and COEN, in prep.). The standard cross is performed in such a way that (1) a sample of diploid cells randomly collected at the end of the cross should

Genetic variation in natural populations of five drosophila species and the hypothesis of the selective neutrality of protein polymorphisms

Abstract: We have studied genetic variation at 30-32 loci coding for enzymes in natural populations of five species of Drosophila. The average proportion of heterozygous loci per individual is 17.7 ± 0.4%. The average proportion of polymorphic loci per population is 69.2 ± 2.6% or 49.8 ± 2.2%, depending on what criterion of polymorphism is used. The following generalizations are advanced: (1) The amount of genetic polymorphism varies considerably from locus to locus. (2) At a given locus, populations of the same species are very similar in the amount and pattern of genetic variation. (3) However, at some loci large differences sometimes occur between local populations of the same species. (4) The amount of variation at a given locus is approximately the same in all five species. (5) When different species are compared, the pattern of the variation is either essentially identical or totally different at a majority of loci. We have tested the hypothesis that protein polymorphisms are selectively neutral by examining four predictions derived from the hypothesis. Our results are at variance with every one of the predictions. We have measured the amount of genetic differentiation, D, between taxa of various degrees of evolutionary divergence. The average value of D is 0.033 for local populations, 0.228 for subspecies, 0.226 for semispecies, 0.538 for sibling species, and 1.214 for morphologically distinguishable species. Our results indicate that a substantial degree of genetic differentiation (22.8 allelic substitutions for every 100 loci) occurs between allopatric populations that have diverged to the point where they might become different species if they were to become sympatric. However, very little additional genetic change is required for the development of complete reproductive isolation. After the speciation process is completed, species continue to diverge genetically from each other.

Analysis of genes controlling f1 sterility in rice by the use of isogenic lines

Abstract: In order to look into the genetic basis of intervarietal F(1) sterility in rice (Oryza sativa L.), a series of backcrosses (up to B(13)) was carried out using Taichung 65 (Japonica type) as the recurrent parent and several Indica varieties as donor parents. A number of "isogenic F(1)-sterile lines" were isolated by test-crossing fertile F(2) plants obtained from the selfing of partly pollensterile backcross segregants. Crossing experiments with the isogenic lines confirmed the author's previous hypothesis that there are sets of duplicate gametic lethals (s genes) and that gametes carrying a double recessive combination (s(1)s(2)) of these deteriorate during development, though in the present hypothesis the genes are considered to affect the development of microspores only. Assuming that Taichung 65 has the genotype s(1)/s(1) + (2)/+(2) and a donor parent (like an isogenic F(1)-sterile line derived from it) has +(1)/+(1)s(2)/s(2), pollen grains with +(1)s(2) have shown a higher fertilizing capacity in the genetic background of Taichung 65 than those with s(1) +(2), while those with +(1) +(2) have a lower fertilizing capacity. This certational advantage of alien genes was considered to be an internal mechanism that helped the development of F(1) sterility relationships among rice varieties. The isogenic F(1)-sterile lines derived from different donor parents each had a set of s genes at different loci. Linkage relations were detected between the s loci and three gene markers.

Mutations affecting sexual conjugation and related processes in Saccharomyces cerevisiae. I. Isolation and phenotypic characterization of nonmating mutants.

Abstract: Nonmating mutants were also isolated from haploid strains of yeast of both mating types. The mutants were characterized with respect to their ability to produce and respond to specific yeast sex factors, their ability to mate at low frequencies, and the ability of the low-frequency diploids to sporulate. Loss of the ability to mate by either mating type was invariably accompanied by the loss of one or more, and in some cases, all, of the above capabilities. The results strongly indicate that the sex factors are functionally involved in the conjugation process.

Mutations affecting sexual conjugation and related processes in Saccharomyces cerevisiae. II. Genetic analysis of nonmating mutants.

Abstract: Rare diploids formed by sterile mutants have been studied by tetrad analysis. Sixteen classes of mutants representing at least five distinct genetic loci have been defined. One group of mutations, isolated only in α, maps at the mating-type locus, while none of the others shows any linkage to mating type. Some of the mutations are nonspecific for mating type, while others act only on a or α. In addition, mutations were found that prevent sporulation when heterozygous in diploids. These appear to be mutations of the mating-type alleles.

Rec-mediated recombinational hot spot activity in bacteriophage lambda. II. A mutation which causes hot spot activity.

Abstract: Crosses have been performed which identify phage mutants (chi) which cause recombinational hot spot activity in λ. The hot spot activity is found in crosses of red- gam- chi- strains in rec+ hosts; in the crosses reported here, both the chi- mutations and the hot spot are located near the right end of the chromosome. The hot spot occurs in standard crosses as well as under conditions which block DNA synthesis, and is dependent on a functional host recB gene.—The chi mutation is shown to be dominant, but the tests do not show whether chi is a gene or a site.

Hairpin-tail: a case of post-reductional gene action in the mouse egg.

Abstract: Hairpin-tail (T(hp)) is a new allele of brachyury on chromosome 17 (linkage group IX) of the mouse. The morphological effects in the heterozygote are on the notochord and the tail. The homozygous abnormal is unknown. T(hp) is unique in that the phenotype of the heterozygote seems to depend on the source of the T(hp) gene. If it is inherited via the egg the phenotype is extreme and death follows in utero. Embryos derived from a T(hp) sperm and a+egg are less abnormal and viable. This is not a simple maternal effect, as T(hp)xT(hp) matings produce two distinct types of heterozygous embryos.

MUTANTS OF YEAST DEFECTIVE IN ISO-1-CYTOCHROME c

Abstract: A medium containing chlorolactate has been devised to enrich for mutants that are unable to utilize lactate for growth, and therefore that may be defective in cytochrome c. Complementation tests of 6,520 chlorolactate-resistant mutants that were obtained spontaneously or induced with UV, ICR-170, or nitrosoimidazolidone resulted in the identification of 195 mutations at the cyc1 locus, which controls the primary structure of iso-1-cytochrome c. These 195 mutants, with 16 cyc1 mutants previously isolated, were examined for total cytochrome c by spectroscopic methods, growth on lactate medium, suppressibility by defined nonsense suppressors, mutational sites by x-ray-induced recombination, ability to revert, and in 86 cases, whether intragenic revertants contain altered iso-1-cytochrome c. Except for the deletion mutant cyc1-1, all of the mutants appeared to contain single-site mutations that could be assigned to at least 35 different sites within the gene. The cyc1 mutants either completely lacked iso-1-cytochrome c or contained iso-1- cytochromes c that were completely or partially nonfunctional. In spite of the fact that the cyc1 mutants obtained by the chlorolactate procedure were selected on the basis of defective function, 68% appeared to completely lack iso-1-cytochrome c. The remaining cyc1 mutants contained below normal amounts of iso-1-cytochromes c. Studies at several incubation temperatures indicated that these nonfunctional iso-1-cytochromes c were thermolabile. It is suggested that the predominant means for abolishing iso-1-cytochrome c by mutations are either through a complete loss, such as produced by chain terminating codons, or impairments through drastic changes of tertiary structure which lead to instability and thermolability.

Linkage disequilibrium in natural populations of Drosophila melanogaster.

Abstract: Two large, stable populations (Texas and Japan) of Drosophila melanogaster were surveyed at 21 allozyme loci on the second and third chromosomes and for chromosomal gene arrangements on those two chromosomes. Over 220 independent gametes were sampled from each population. The types and frequencies of the surveyed genetic variation are similar to those observed previously and suggest only slight differentiation among geographically distant populations. Linkage disequilibrium among linked allozymes loci is only slightly, if at all, detectable with these sample sizes. Linkage disequilibrium between linked inversions and allozymes loci is common especially when located in the same arm. These disequilibria appear to be in the same direction for most comparisons in the two population samples. This result is interpreted as evidence of similar selective environments (ecological and genetic) in the two populations. It is also noted that the direction of these linkage disequilibria appears to be oriented with respect to the gene frequencies at the component loci.

Selection for high mutation rates in chemostats.

Abstract: Competition experiments in chemostats show that mutator populations of Escherichia coli are more fit than wild type. The increased fitness can be explained by the appearance of new mutants better adapted to the chemostat environment. Fitness values vary between chemostats and are strongly correlated (P

Lack of chemically induced mutation in repair-deficient mutants of yeast.

Abstract: Two genes, rad6 and rad9 , that confer radiation sensitivity in the yeast Saccharomyces cerevisiae also greatly reduce the frequency of chemically-induced reversions of a tester mutant cyc1-131 , which is a chain initiation mutant in the structural gene determining iso-1-cytochrome c . Mutations induced by ethyl methanesulfonate (EMS), diethyl sulfate (DES), methyl methanesulfonate (MMS), dimethyl sulfate (DMS), nitroquinoline oxide (NQO), nitrosoguanidine (NTG), nitrogen mustard (HN2), β-propiolactone, and tritiated uridine, as well as mutations induced by ultraviolet light (UV) and ionizing radiation were greatly diminished in strains homozygous for either the rad6 or rad9 gene. Nitrous acid and nitrosoimidazolidone (NIL), on the other hand, were highly mutagenic in these repair-deficient mutants, and at low doses, these mutagens acted with about the same efficiency as in the normal RAD strain. At high doses of either nitrous acid or NIL, however, reversion frequencies were significantly reduced in the two rad mutants compared to normal strains. Although both rad mutants are immutable to about the same extent, the rad9 strains tend to be less sensitive to the lethal effect of chemical mutagens than rad6 strains. It is concluded that yeast requires a functional repair system for mutation induction by chemical agents.

Gene Flow and Genetic Differentiation

Abstract: A brief analysis is presented for the effects of gene flow upon genetic differentiation within and between populations generated by mutation and drift. Previous results obtained with the "island" model are developed into a form that lends itself to biological interpretation. Attention is focused upon the effective local population size and the ratio of the genetic identity of two genes in different populations to that of two genes in the same population. The biological significance of this ratio, which is independent of population size, is discussed. Similarities between the results of this model and those of the "stepping-stone" model are noted.

Microdifferentiation in a natural population of Drosophila melanogaster to alcohol in the environment.

Abstract: Strains of D. melanogaster derived from a vineyard population were more resistant to alcohol in the environment than strains from a population derived from an area removed from the vineyard. Within the vineyard population those strains most closely associated with alcohol in the environment in the cellar were more resistant than those collected outside the cellar. There was evidence of gene flow between the inside and outside cellar components of this population, but microdifferentiation had occurred within the cellar in spite of this. The adaptation appears to be independent of the ADH system and involves both additive and dominance genetic effects. D. simulans , a species not found in the cellar and susceptible to the presence of alcohol, showed no differentiation between vineyard and removed populations.

Divergent operons and the genetic structure of the maltose B region in Escherichia coli K12.

Abstract: Complementation and polarity suppression data are interpreted in terms of the genetic structure of the maltose B region. It is proposed that this region comprises two divergent operons. One operon includes malK, a cistron involved in maltose permeation, and lamB the only known cistron specifically involved in lambda receptor synthesis. The other operon includes malJ(1) and malJ(2) which are most probably two different cistrons, both involved in maltose permeation*. It is further assumed that expression of the two operons is controlled by malT, the positive regulatory gene of the maltose system, located in the malA region. The target(s) for the action of the malT product is (are) most likely to be located between malJ(1) and malK. There is an indication that the two operons might overlap in the region of their promoters. The structure of such an overlap as well as the possible function of the products of the different cistrons in malB are briefly discussed.

Enzyme Variability in Natural Populations of DAPHNIA MAGNA II. Genotypic Frequencies in Permanent Populations

Abstract: In permanent habitats populations of the cyclical parthenogen, Daphnia magna, reproduce by continued parthenogenesis and are subject to only sporadic sexual recruitment. The genetic effects of this breeding system have been investigated by analyzing allozyme frequencies in thirteen populations of D. magna.—Genotypic frequencies at polymorphic loci characteristically deviated markedly from Hardy-Weinberg proportions and gametic phase imbalance between loci was frequent. Genotypic frequencies were subject to violent, selectively determined oscillations over short periods of time. These observations suggest that permanent populations of D. magna ordinarily consist of a limited number of highly structured genotypes. The adaptational advantages offered by such structuring may have been a major selective factor favoring the evolution of cyclical parthenogenesis.

Mitochondrial Genetics. VI the Petite Mutation in SACCHAROMYCES CEREVISIAE: Interrelations between the Loss of the ρ+ Factor and the Loss of the Drug Resistance Mitochondrial Genetic Markers

Abstract: The survival of the ρ+ factor and of DrugR mitochondrial genetic markers after exposure to ethidium bromide has been studied. A technique allowing the determination of DrugR genetic markers among a great number of both grande and petite colonies has been developed. The results have been analyzed by the target theory. The survival of the ρ+ factor is always less than the survival of any DrugR genetic marker. The survivals of CR and ER are similar to each other, while that of OR is greater than that of the other two DrugR markers. All possible combinations of DrugR markers have been found among the ρ- petite cells induced, while the only type found among the grande colonies is the preexisting one. The loss of the CR and ER genetic markers was found to be the most frequently concomitant, while the correlation between the loss of the OR marker and the other two DrugR markers is less strong. Similar results have been obtained after U.V. irradiation. Interpretations concerning the structure of the yeast mitochondrial genome are given and hypotheses on the mechanism of petite mutation discussed.

Are mitotic functions required in meiosis

Abstract: Sporulation of diploid yeasts (Saccharomyces cerevisiae), homozygous or heterozygous for temperature-sensitive mitotic cell-cycle mutations, was examined at the restrictive and permissive temperatures. Twenty genes, represented by 32 heterozygotes and 60 homozygotes, were divided into three groups, showing (i) normal sporulation, (ii) no sporulation at the restrictive temperature but normal sporulation at the permissive temperature, (iii) no sporulation at both temperatures. Group (i) as well as several other strains were tested for their meiotic behavior with regard to intragenic recombination and haploidization. The conclusion reached was that all the mitotic nuclear-division and DNA-synthesis functions were required in meiosis. The only cell-division mutations not to affect meiosis were in three cytokinesis loci and in one budemergence locus.

The Genetic Structure of Natural Populations of DROSOPHILA MELANOGASTER. Xi. Genetic Variability in a Local Population

Abstract: Six hundred and ninety-one second chromosomes were extracted from a Raleigh, North Carolina population, and the following experimental results were obtained: (1) Salivary gland chromosomes of all lines were observed and the number of inversion-carrying chromosomes was 130, among which 76 carried In(2R)NS , 36 carried In(2L)t , 4 carried In(2L)t and In(2R)NS , and 14 carried different kinds of rare inversions. (2) Viabilities of homozygotes and heterozygotes were examined. The frequency of lethal-carrying chromosomes was 275/691 (or 0.398):70/130 (or 0.538) in inversion-carrying chromosomes and 205/561 (or 0.365) in inversion-free chromosomes. The former is significantly higher than the latter. The average homozygote viability was 0.4342 including lethal lines and 0.7163 excluding those, the average heterozygote viability being 1.0000. The detrimental load to lethal load ratio (D:L ratio) was 0.334/0.501 = 0.67. The average viability of lethal heterozygotes was less than that of lethal-free heterozygotes, significantly in inversion-free individuals but not significantly so in inversion-carrying individuals. Inversion heterozygotes seem to have slightly better viability than the inversion-free heterozygotes on the average, but not significantly so. (3) The average degree of dominance of viability polygenes was estimated to be 0.293 ± 0.071 for all heterozygotes whose component chromosomes had better viabilities than 0.6 of the average heterozygote viability, 0.177 ± 0.077 for inversion-free heterozygotes and 0.489 ± 0.082 for inversion heterozygotes. (4) Mutation rates of viability polygenes and lethal genes were estimated on the basis of genetic loads and average degrees of dominance of lethal genes and viability polygenes. Estimates were very close to those obtained by direct estimation. (5) Possible overdominance and epistasis were detected, but the magnitude must be very small. (6) The effective size of the population was estimated to be much greater than 10,000 by using the allelism rate of lethal-carrying chromosomes (0.0040) and their frequency.—On the basis of these findings and the comparison with the predicted result (Mukai and Maruyama 1971), the mechanisms of the maintenance of genetic variability in the population are discussed.

Gene conversion of deletions in the his4 region of yeast.

Abstract: A selection procedure has been devised which allows the recovery of deletions of the his4 region of Saccharomyces cerevisiae. Many deletions were obtained by this procedure and were characterized genetically and biochemically. These deletions permit the construction of a linear map of the his4A and his4B region. A deletion which was large on this genetic map reduced the size of the his4 gene product. Tetrad analyses revealed that deletions can affect the conversion frequency of other alleles at his4. Analysis of reciprocal recombination in conversion tetrads showed that the order of genes on chromosome III is: centromere-leu2-his4A-his4C. This means that in his4 transcription and translation proceed away from the centromere.

On recombination-defective meiotic mutants in Drosophila melanogaster.

Abstract: The genetic effects of four recombination-defective meiotic mutants in D. melanogaster on recombination, segregation and the relationship between the two have been examined. The results suggest the following. (1) The anomalous meiotic segregation observed in females carrying recombination-defective meiotic mutants is a normal consequence of the reduction in exchange; each recombination-defective mutant can, therefore, be defined by a single lesion in the control of recombination. (2) Of the operations used to date to characterize this lesion, the most informative is whether the decrease in recombination is uniform along the chromosome arm or nonuniform; in particular, if the formation of recombinants is visualized as a two-step process consisting of the establishment of possible exchange points (exchange preconditions) followed by exchange itself, then mutants that uniformly decrease crossing over involve defects in the second step while mutants that result in a nonuniform decrease involve defects in the establishment of exchange preconditions. (3) Of the fourteen loci identified by recombination-defective meiotic mutants, only one (with two alleles) is involved in exchange itself; the others all reduce recombination most drastically in distal regions, suggesting that the establishment of exchange preconditions involves polar processes. (4) A very general description of the polar establishment of exchange preconditions is presented; this description has the property that if a precondition meiotic mutant affects interference, the coefficient of coincidence will be increased in proportion to the decrease in recombination which is what is observed for all recombination-defective meiotic mutants studied to date.

The genetic structure of natural populations of drosophila melanogaster. xii. linkage disequilibrium in a large local population

Abstract: Seven hundred and three second chromosomes were extracted from a Raleigh, North Carolina population of Drosophila melanogaster in 1970. Additionally, four hundred and eighty-nine third chromosomes were extracted from a large cage population founded from the flies in the 1970 Raleigh collection. The α glycerol-3-phosphate dehydrogenase-1, malate dehydrogenase-1, alcohol dehydrogenase, and α amylase loci were studied from the second chromosomes, and the esterase-6, esterase-C, and octanol dehydrogenase loci were analyzed from the third chromosomes. Inversions, relative viability and fecundity were studied for both classes of chromosomes. The following significant findings were obtained: (1) All loci examined were polymorphic or had at least two alleles at appreciable frequencies. Analysis of the combined data from this experiment with that of Mukai, Mettler and Chigusa (1971) revealed that the frequencies of the genes in the second chromosomes collected in early August were approximately the same over three years. (2) Linkage disequilibria between and among isozyme genes inter se were not detected except in a few cases which can be considered due to non-random sampling. (3) Linkage disequilibria between isozyme genes and polymorphic inversions were detected when the recombination values between the breakage points of the inversions and the genes in question were small. In only a few cases, were second and third order linkage disequilibria including polymorphic inversions detected. (4) Evidence for either variation among genotypes within loci or cumulative effects of heterozygosity was found for viability and fecundity. As a result of these findings, it was tentatively concluded that although selection might be perceptibly operating on some polymorphic isozyme loci, most of the polymorphic isozyme genes are selectively neutral or near-neutral in the populations studied.