Showing papers in "Genetics in 1978"

Estimation of average heterozygosity and genetic distance from a small number of individuals

Abstract: The magnitudes of the systematic biases involved in sample heterozygosity and sample genetic distances are evaluated, and formulae for obtaining unbiased estimates of average heterozygosity and genetic distance are developed. It is also shown that the number of individuals to be used for estimating average heterozygosity can be very small if a large number of loci are studied and the average heterozygosity is low. The number of individuals to be used for estimating genetic distance can also be very small if the genetic distance is large and the average heterozygosity of the two species compared is low.

The homozygosity test of neutrality

Abstract: An earlier paper showed that the homozygosity (of a population or sample) was a good statistic for testing departures from selective neutrality in the direction of heterozygote advantage or disadvantage. It is here shown that homozygosity is also influenced by the presence of deleterious alleles and by other departures from neutrality, but at a lower order of magnitude of effect if the selection coefficients are of the same small order of magnitude. Tables are provided for the significance points and moments of the homozygosity, under the null hypothesis of neutrality.

Osmotic avoidance defective mutants of the nematode Caenorhabditis elegans.

Abstract: A wild-type strain of the nematode Caenorhabditis elegans has been shown to avoid high concentrations of a number of sugars and salts. Individual and population assays for this response were developed and mutants were selected for their inability to avoid high concentrations of fructose or NaCl. Seven nonavoiding mutants representing six complementation groups were isolated and characterized. Genetic studies indicate that the mutants each carry a single recessive mutation responsible for the defective osmotic avoidance behavior. The map locations of the six complementation groups identified by these mutations have been determined. Mutants isolated for their inability to avoid fructose are also unable to avoid NaCl and vice versa. The mutants move normally, exhibit normal touch sensitivity, and, like wild type, follow isotherms in a radial thermal gradient. All of the mutants are at least partially defective in the attraction to sodium chloride exhibited by wild type. None of the mutants is temperature sensitive, and all exhibit defective osmotic avoidance behavior as young L1 larvae. Preliminary anatomical studies indicate selective sensory neuron changes in at least one mutant.

Two closely linked mutations in drosophila melanogaster that are lethal to opposite sexes and interact with daughterless

Abstract: A new spontaneous mutation named Sex-lethal, Male-specific #1 (SxlM1) is described that is lethal to males, even in the presence of an Sxl+ duplication. Females homozygous for SxlM1 are fully viable. This dominant, male-specific lethal mutation is on the X chromosome approximately 0.007 map units to the right of a previously isolated female-specific mutation, Female-lethal, here renamed Sex-lethal, Female-specific #1 (SxlF1). SxlM1 and SxlF1 are opposite in nearly every respect, particularly with regard to their interaction with the maternal effect of the autosomal mutation, daughterless (da). Females that are homozygous for da produce defective eggs that cannot support female (XX) development. A single dose of SxlM1 enables daughters to survive this da female-specific lethal maternal effect. A duplication of the Sxl locus weakly mimics this action of SxlM1. In contrast, SxlF1 and a deficiency for Sxl, strongly enhance the female-lethal effects of da. The actions of SxlM1 and SxlF1 are explained by a model in which expression of the Sxl locus is essential for females, lethal for males, and under the control of a product of the da locus. It is suggested that SxlM1 is a constitutive mutation at the Sxl locus.

Heterogeneity of maize cytoplasmic genomes among male-sterile cytoplasms

Abstract: Maize mitochondrial and chloroplast DNA9s were prepared from normal (fertile) lines or single crosses and from members of the T, C, and S groups of male-sterile cytoplasms. Restriction endonucleases Hin dIII, Bam I, Eco RI, and Sal I were used to restrict the DNA, and the resultant fragments were electrophoresed in agarose gels. The results show that the N (fertile), T, C, and S cytoplasms each contained distinct mitochondrial DNA (mtDNA). These distinctive patterns were unaffected by nuclear genotype. No evidence of paternal inheritance of mtDNA was observed. Chloroplast DNA (ctDNA) from the N, C, and T cytoplasms was indistinguishable by Hin dIII, Sal I, or Eco RI endonuclease digestion. The S cytoplasm ctDNA, however, was slightly different from that of other cytoplasms, as indicated by a slight displacement of one band in Hin dIII digests. The molecular weight of maize ctDNA was estimated to be as high as 88 x 10 6 . Estimates of the minimum molecular weight of maize mtDNA ranged from 116-131 x 10 6 , but the patterns were to complex for an unambiguous determination. Based on Hin dIII data, a comparison of the molecular weight of mtDNA bands common to the N, T. C, and S cytoplasms suggests that C cytoplasm most closely resembles N cytoplasm. The T and S sources are more divergent from the C and N cytoplasms. These results indicate a possible gradation of relatedness among male-sterile cytoplasms. The marked variation in mtDNA, with apparently less variation in ctDNA, represents circumstantial, but compelling, evidence that mtDNA may be involved in the male sterility and disease susceptibility traits in maize.

Properties of the translocatable tetracycline-resistance element Tn10 in Escherichia coli and bacteriophage lambda.

Abstract: A number of independent insertions into bacteriophage lambda of the translocatable tetracycline-resistance element Tn10 have been isolated and characterized. The physical positions and relative orientations of several such insertions were determined. Two independent insertions appear to lie in the same orientation at or very near the same site in the cI gene, and two more lie in opposite orientations at or near the same position in or near the rex gene. Insertions in or near genes cI, rex, and cIII have been characterized genetically for their effects on expression of nearby genes. Tn10 appears to exert a polar effect on expression of distal genes when it is inserted within an operon, even when expression of that operon is under the influence of lambda N-function. In addition, Tn10 insertions in rex appear to influence in some way expression of an "upstream" gene, cI. Lambda derivatives carrying Tn10 give rise to spontaneously occurring, tetracycline-sensitive deletions at high frequencies. It is likely that formation of these deletions is promoted in some way by the Tn10 element. Lambda::Tn10 phages carrying a Tn10 element that has undergone several successive cycles of translocation since its first isolation and characterization have been analyzed. The results confirm that Tn10 often retains its physical and functional integrity during many cycles of translocation. Lambda derivatives carrying Tn10 have been used to generate insertions of Tn10 in the chromosome of Escherichia coli. This process is independent of recA function, and seems to be quite analogous to the translocation of Tn10 in Salmonella typhimurium as studied previously.

Estimation of life cycle components of selection in an experimental plant population.

Abstract: Viability and fertility components of selection associated with linkage blocks marked by four electrophoretically detectable loci were estimated in an experimental population of barley [Composite Cross V (CCV)]. The intensity of selection affecting the distribution of pollen types in the outcross pool was also estimated and comparisons were made between the selective values of genes in the pools of uniting ovules and pollen. The estimates show that selection was intense at various stages of the life cycle and that viability and fertility components often opposed one another. Estimates of viability and fertility components of selection were also extended to the three-locus level. The multilocus estimates reveal large differences in viability and fertility among homozygous genotypes. It is concluded that strong selection operates at all life cycle stages in CCV, although often in differing directions.

Heterosis as an explanation for large amounts of genic polymorphism.

Abstract: By using both numerical and analytical approaches, we have shown that heterosis alone is not a mechanism for maintaining many alleles segregating at a locus. Even when all heterozygous are more fit than all homozygotes, the proportion of fitness arrays that will lead to a stable, feasible equilibrium of more than 6 or 7 alleles is vanishingly small. More alleles can be maintained if, in addition to heterosis, it is assumed that there is very little variation in fitness from heterozygote to heterozygote, with the ratio of mean heterosis to standard deviation of fitness among heterozygotes in the neighborhood of 10. When such conditions hold, the allelic frequency distribution and equilibrium will be very uniform, with all alleles very close to equal frequency (see PDF). It is much more likely that stable equilibria for multiple alleles will be best explained by multiple niche selection.

Glycolysis mutants in Saccharomyces cerevisiae.

Abstract: Mutants have been isolated in S. cerevisiae with the phenotype of growth on pyruvate but not on glucose, or growth on rich medium with pyruvate but inhibition by glucose. Screening of mutagenized cultures was either without an enrichment step, or after enrichment using the antibiotic netropsin (Young et al. 1976) or inositol starvation ( Henry, Donahue and Culbertson 1975). One class of mutants lacked pyruvate kinase (pyk), another class had all the enzymes of glycolysis, and one mutant lacked phosphoglucose isomerase (pgi, Maitra 1971). Partial reversion of pyruvate kinase mutants on rich medium containing glucose gave double mutants now also lacking hexokinase (hxk ), phosphofructokinase (pfk), or several enzymes of glycolysis (gcr). In diploids the mutations were recessive. pyk, pgi, pfk , and gcr segregated 2:2 from their wild-type alleles. PYK hxk, PYK pfk, and PYK gcr segregants grew on glucose.

Developmental Analysis of the Achaete-Scute System of DROSOPHILA MELANOGASTER

Abstract: The interpretation of the wild-type function of a gene depends on our knowledge of the phenotype caused by its absence. We have first defined the genetic extent of the achaete-scute system by studying the phenotype of different terminal and intercalary deficiencies including these genes. When these deficiencies were lethal, we have defined the phenoeffective phase of lethality and studied their phenotype in genetic mosaics (gynandromorphs and mitotic recombination clones). The achaete-scute system affects two functions, one necessary for the differentiation of the embryonic (central?) nervous system and the other necessary for the differentiation of peripheral nervous elements of the chaetes and sensillae of the adult cuticle. The possibility that these functions correspond to differential expression of a single mechanism is discussed.

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

Abstract: 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.

Population dynamics of the segregation distorter polymorphism of drosophila melanogaster

Abstract: Two two-locus models of the population dynamics of the segregation distortion (SD) polymorphism of Drosophila melanogaster are described. One model is appropriate for understanding the population genetics of SD in nature, whereas the other is a special case appropriate for understanding an artificial population that has been extensively analysed. The models incorporate the general features of the Sd and Rsp loci which form the core of the SD system. It is shown that the SD polymorphism can be established only when there is sufficiently tight linkage between Sd and Rsp. An approximate treatment, valid for tight linkage, is given of all the equilibria of the system and their stabilities. It is shown that the observed composition of natural and artificial populations with respect to the Sd and Rsp loci is predicted well by the model, provided that restrictions are imposed on the fertilities of certain genotypes. Highly oscillatory paths towards equilibrium are usually to be expected on the basis of this model. The selection pressures on inversions introduced into this system are also investigated.

A sex-linked gene controlling the onset of sexual maturity in female and male platyfish (xiphophorus maculatus), fecundity in females and adult size in males

Abstract: A sex-linked gene, P, controls the onset of sexual maturity in the platyfish, Xiphophorus maculatus. The activity of this gene is correlated with the age and size at which the gonadotropic zone of the adenohypophysis differentiates and becomes physiologically active. Immature fish of all genotypes grow at the same rate; however, as adults, males with "early" genotypes are significantly smaller than males of "late" genotypes, since growth rate declines strongly under the influence of androgenic hormone. Five alleles, P(1)... P(5), have been identified from natural populations that under controlled conditions cause gonad maturation between eight and 73 weeks. P(1)P(1) males become mature at eight weeks and 21 mm, P(2)P(2) and P(3)P(3) males between eleven and 13.5 weeks and 25 to 29 mm, and P(4)P(4) males at 25 weeks and 37 mm. Since P(5) is X-linked, no males homozygous for P(5) could be produced. The difference between P(2) and P(3) is largely based upon their interaction with P(5). P(3)P(5) males mature at 17.5 weeks and 33.5 mm and P(2)P(5) males at 28 weeks and 38 mm. The rate of transformation of the unmodified anal fin into a gonopodium, which is under androgenic control, is directly related to the age at initiation of sexual maturity, ranging from 3.2 weeks in P(1)P(1) males to seven weeks in P(2)P( 5) males. These differences may reflect different levels of circulating gonadotropic and androgenic hormones.-In two genotypes of females, initiation of vitellogenesis was closely correlated with size and this critical size was independent of age (e.g., 21 mm for P(1)P(1 )). In a third genotype (P(1)P(5)) the minimum size for vitellogenesis decreased with increasing age, so that females would mature as early as eleven weeks, provided they had attained at least 29 mm, but at 25 weeks even females as small as 23 mm possessed ripe gonads. For P(5)P(5) females, which become mature between 34 and 73 weeks of age, there is no correlation between size and initiation of vitellogenesis. In all four genotypes of females examined, egg number is strongly correlated with size, but the regression of egg number on standard length is distinct for each genotype. Late maturation of P(5)P( 5) females is not offset by an increased number of eggs; for this genotype there is a strong negative correlation between age and number of eggs. Heterozygous fish always mature later than those homozygous for the "earlier" allele. The site of action of the P locus could be the pituitary gland, the hypothalamus or higher centers of the brain where peripheral information is transduced into an appropriate signal required for the activation of the hypothalamus-pituitary-gonadal axis. The P gene could also control the peripheral information. The platyfish may be a useful model to test theories concerning the evolution of life history strategies.

Crossover suppressors and balanced recessive lethals in Caenorhabditis elegans.

Abstract: Two dominant suppressors of crossing over have been identified following X-ray treatment of the small nematode C. eZegans. They suppress crossing over in linkage group ZZ (LGZZ) about 100-fold and 50-fold and are both tightly linked to LGZZ markers. One, called C1, segregates independently of all other linkage groups and is homozygous fertile. The other is a translocation involving LGZZ and X. The translocation also suppresses rrossing over along the right half of X and is homozygous lethal. CI has been used as a balancer of LGZZ recessive lethal and sterile mutations induced by EMS. The frequencies of occurrence of lethals and steriles were approximately equal. Fourteen mutations were assigned to complementation groups and mapped. They tended to map in the same region where LGZZ visibles are clustered. HE nematode Caenorhabditis elegans is gaining favor as an organism in Twhich to study the genetic basis of animal development and behavior, primarily because of its relative cellular simplicity (SULSTON and HORVITZ 1977) and its suitability for genetic analysis (BRENNER 1974). Most work with C. elegans is thus based on the idea that the detailed analysis of mutants, both at the cellular level and the molecular level, will prove to be an important approach in gaining an understanding of the genetic programs controlling development. Since many of the genes in C. eIegans play indispensable roles in development, temperature-sensitive mutants are being utilized extensively (see, for example, EPSTEIN and THOMPSON 1974; HIRSH and VANDERSLICE 1976). Another approach is to make use of recessive lethal and sterile mutations, which of course must be maintained in heterozygous stocks. Each such heterozygote should be made distinguishable phenotypically from the homozygous wild type by using a suitably marked balancer. Furthermore, complementation and mapping of lethals and steriles would be greatly facilitated by using visibles that are tightly linked to the lethals. The most useful balancers, then, recombine as little as possible within the region they balance, which means they are often made to carry crossover-suppressing properties. In a previous paper (HERMAN, ALBERTSON and BRENNER 1976), unlinked duplications of a part of the X chromosome of C. elegans were identified, and their potential use as balancers was discussed. Indeed, one of these duplications, Dp (X;V)I, has now been used to balance a

The alcohol dehydrogenase polymorphism in populations of Drosophila melanogaster. I. Selection in different environments.

Abstract: The allozyme polymorphism at the alcohol dehydrogenase locus in Drosophila melanogaster was studied in order to obtain experimental evidence about the maintenance of this polymorphism. Populations started with different initial allele frequencies from homozygous F and S lines showed a convergence of frequencies on regular food at 25°, leading to values equal to those in the base populations. These results were interpreted as due to some kind of balancing selection. In populations kept at 29.8°, a lower equilibrium F frequency was attained. Addition of ethanol and some other alcohols to the food gave a rapid increase in F frequency, and high humidity decreased the F frequency slightly. Combination or alternation of ethanol and high humidity had variable effects in the populations tested. For a further analysis of the allele-frequency changes, estimates were obtained for egg-to-adult survival under different conditions and for adult survival on ethanol-supplemented food. On ethanol food (both at regular and high humidity), egg-to-adult survival of SS homozygotes was considerably lower than that of the FF and FS genotypes. Under regular conditions of food, temperature and humidity, a tendency to heterozygote superiority was observed, while at high humidity a relative high survival of SS was noticed in some tests. Adult survival of SS was lower than that of FF, but FS was generally intermediate, though the degree of dominance differed between populations. The results are consistent with the hypothesis of the occurrence of selection at the Adh locus.

Characterization of temperature-sensitive, fertilization-defective mutants of the nematode caenorhabditis elegans

Abstract: The isolation and characterization of three Caenorhabditis elegans temperature-sensitive mutants that are defective at fertilization are described. All three are alleles of the gene fer-1. At the restrictive temperature of 25°, mutant hermaphrodites make sperm and oocytes in normal numbers. No oocytes are fertilized, although they pass through the spermatheca and uterus normally. The oocytes can be fertilized by sperm transferred by wild-type males, indicating that the mutant defect is in the sperm. The temperature-sensitive period for the mutants coincides with spermatogenesis. Sperm made by mutants at 25° cannot be distinguished from wild-type sperm by light microscopy. The sperm do contact oocytes in mutant hermaphrodites, but do not fertilize. Mutant sperm appear to be nonmotile. Mutant males are also sterile when grown at 25°. They transfer normal numbers of sperm to hermaphrodites at mating, but these sperm fail to migrate to the spermatheca and are infertile. The phenotype of these mutants is consistent with a primary defect in sperm motility, but the cause of this defect is not known.

Isolation, genetic mapping and some characterization of a mutation in escherichia coli that affects the processing of ribonucleic acid

Abstract: Temperature-sensitive mutants were isolated from an rnc (RNase III-) strain of Escherichia coli , and their rRNA metabolism was analyzed on 3% polyacrylamide gels. One of these mutants was unable to produce 23S and 5S rRNAs at the nonpermissive temperature. When an rnc + allele was introduced to this strain, it remained temperature sensitive. At the nonpermissive temperature, this strain could then produce 23S rRNA but was unable to make normal levels of 5S rRNA. In matings and transduction experiments, the defect in rRNA metabolism and temperature sensitivity behaved as a syndrome caused by a single point mutation, which was mapped at min 23.5 on the E. coli chromosome. This mutation probably affects an enzyme, ribonuclease E (RNase E), which introduces a cut in the nascent rRNA transcript between the 23S and the 5S rRNA cistrons. The mutation rne is recessive with respect to temperature sensitivity and the pattern of rRNA. Revertants able to grow at 43° and with normal metabolism of rRNA were isolated; genetic analysis showed that they do not contain the original rne mutation, suggesting that they were true revertants. By combining the rne mutation with an rnc mutation, double rnc rne strains were synthesized, which behaved very similarly to the original rnc strain from which the rne mutation was isolated. Such strains have RNA metabolism that is similar to that of rnc strains at permissive temperatures, but at the nonpermissive temperature they fail to synthesize p23, m23 and 5S rRNAs. Thus, the experiments reported here, together with previous studies, suggest the existence of a new processing ribonuclease activity in Escherichia coli , which is called ribonuclease E.

Ultraviolet-induced reversion of cyc1 alleles in radiation sensitive strains of yeast. II. rev2 mutant strains.

Abstract: The range of specificity of the rev2–1 mutation, an allele that reduces the frequency of ochre revertants induced by UV in Saccharomyces cerevisiae (Lemontt 1971a), has been investigated by examining its influence on the reversion of eleven well-defined and contrasting cyc1 mutations. We have shown, in support of a suggestion of Lemontt (1971a), that the REV2 gene product is concerned only with the reversion of ochre alleles; it plays virtually no role in the reversion of amber, missense or frameshift mutations. We have also shown that its effect is specific and confined to only some highly revertible ochre alleles. The REV2 gene product appears to enhance reversion at these sites by facilitating the conversion of two otherwise nonmutagenic photo-products into a single premutational lesion. UV-induced killing of rev2–1 strains was found to be significantly greater on fermentable rather than on nonfermentable media.

Genetic and Biochemical Basis of Enzyme Activity Variation in Natural Populations. I. Alcohol Dehydrogenase in DROSOPHILA MELANOGASTER

Abstract: Recent studies by various authors suggest that variation in gene regulation may be common in nature, and might be of great evolutionary consequence; but the ascertainment of variation in gene regulation has proven to be a difficult problem. In this study, we explore this problem by measuring alcohol dehydrogenase (ADH) activity in Drosophila melanogaster strains homozygous for various combinations of given second and third chromosomes sampled from a natural population. The structural locus (Adh) coding for ADH is on the second chromosome. The results show that: (1) there are genes, other than Adh, that affect the levels of ADH activity; (2) at least some of these "regulatory" genes are located on the third chromosome, and thus are not adjacent to the Adh locus; (3) variation exists in natural populations for such regulatory genes; (4) the effect of these regulatory genes varies as they interact with different second chromosomes; (5) third chromosomes with high-activity genes are either partially or completely dominant over chromosomes with low-activity genes; (6) the effects of the regulatory genes are pervasive throughout development; and (7) the third chromosome genes regulate the levels of ADH activity by affecting the number of ADH molecules in the flies. The results are consistent with the view that the evolution of regulatory genes may play an important role in adaptation.

Nonessential Sequences, Genes, and the Polytene Chromosome Bands of DROSOPHILA MELANOGASTER.

Abstract: From earlier work, there appears to be an underlying one-to-one correspondence of polytene chromosome bands and complementation groups within a sizeable, continuous X-chromosome segment, 3A1–3C7 ( Judd, Shen and Kaufman 1972; Lefevre and Green 1972). However, most of the data supporting this one-to-one relation of bands and genes were gathered from mutants that upset vital functional units, thus leading to lethality. Among this series of mutants, only four loci, zeste, white, roughest and verticals, have no known lethal alleles. If phenotypic changes less drastic than lethality result from the loss of other chromosomal segments, they probably would not have been recognized in the earlier studies.—We report here some chromosomal sequences localized in 3A, 3B, and 3C whose loss effects no lethal change in the development of the animal. A portion of the 3A3–3A4 region can be disrupted in a nonlethal fashion, yet this sequence does not seem to be a part of either the zeste locus or l(1)zw1, which are known to be located in these bands. Two more complementation groups have been discovered that have no lethal alleles and map to 3B4–3B6; a third falls within 3B1–2. The loss of a sequence in 3C2–3 is tolerated without any genetically observable effect. Between 3C7 and the boundary of 3D there is at least one more sequence that behaves in this manner.—The discovery of these units, which are not allelic to any of the loci previously known, makes it clear that division 3B contains more genes (i.e., complementation groups) than polytene chromosome bands, while portions of 3A and 3C seem to have no functional significance. Accordingly many polytene chromosome bands may be composites of several complementing functional units. This investigation also indicates that there are chromosomal segments that are seemingly dispensible and thus function in a manner that is difficult or impossible to define with available methods.

Influence of Maternal Phenotype on Metabolic Differentiation of Agouti Locus Mutants in the Mouse

Abstract: The results of extensive breeding experiments indicate that the phenotypic differentiation of embryos carrying the viable yellow, A vy, or mottled, am, mutations is influenced to a major extent by the agouti locus genotype and the strain genome of the dam. The Avy/a and am/a genotypes are each expressed in a spectrum of coat color phenotypes. These can be grouped into two classes, mottled and pseudoagouti.—In a reciprocal cross of C57BL/6JNIcrWf and AM/Wf-am/am mice, 29.5% of the offspring of C57BL/6 dams were of the pseudoagouti phenotype, whereas no pseudoagouti offspring were produced by AM strain dams.—Mottled yellow Avy/a mice become obese and tumor formation is enhanced in these mice in comparison with the lean pseudoagouti Avy/a siblings.—In two different reciprocal crosses using four different inbred strains, the proportion of pseudoagouti Avy/a offspring differed according to the strain of the dam. Regardless of strain, mottled yellow A vy/a dams produced significantly fewer pseudoagouti A vy/a offspring than did black a/a dams.—The data suggest that metabolic differentiation of Avy/a zygotes into phenotypic classes with different susceptibilities to obesity and tumor formation is influenced to a considerable degree by the metabolic characteristics of the oviductal and uterine environment of the dam.

Maintenance of Genetic Variability under the Joint Effect of Mutation, Selection and Random Drift.

Abstract: Formulae are developed for the distribution of allele frequencies (the frequency spectrum), the mean number of alleles in a sample, and the mean and variance of heterozygosity under mutation pressure and under either genic or recessive selection. Numerical computations are carried out by using these formulae and Watterson9s (1977) formula for the distribution of allele frequencies under overdominant selection. The following properties are observed: (1) The effect of selection on the distribution of allele frequencies is slight when 4 Ns ≤ 4, but becomes strong when 4 Ns becomes larger than 10, where N denotes the effective size and s the selective difference between alleles. Genic selection and recessive selection tend to force the distribution to be U-shaped, whereas overdominant selection has the opposite tendency. (2) The mean total number of alleles in a sample is much more strongly affected by selection than the mean number of rare alleles in a sample. (3) Even slight heterozygote advantage, as small as 10 -5 , increases considerably the mean heterozygosity of a population, as compared to the case of neutral mutations. On the other hand, even slight genic or recessive selection causes a great reduction in heterozygosity when population size is large. (4) As a test statistic, the variance of heterozygosity can be used to detect the presence of selection, though it is not efficient when the selection intensity is very weak, say when 4 Ns is around 4 or less. A model, which is somewhat similar to Ohta9s (1976) model of slightly deleterious mutations, has been proposed to explain the following general patterns of genic variation: (i) There seems to be an upper limit for the observed average heterozygosities. (ii) The distribution of allele frequencies is U-shaped for every species surveyed. (iii) Most of the species surveyed tend to have an excess of rare alleles as compared with that expected under the neutral mutation hypothesis.

Testing Hypotheses about Linkage Disequilibrium with Multiple Alleles.

Abstract: For loci with multiple alleles, hypotheses about linkage disequilibrium may be tested on the complete set of gametic data, or on various collapsed sets of data. Collapsing data into a few alleles at each locus can change the power of the tests, as implied in a recent paper by Zouros, Golding and Mackay (1977). We show that the nature of such changes can be found from properties of the noncentral chi-square distribution, and that the magnitude and direction of these changes depend on the levels of linkage disequilibria, allelic frequencies and degrees of freedom.

Dynamics of correlated genetic systems. IV. Multilocus effects of ethanol stress environments

Abstract: Four replicate populations of Drosophila melanogaster, two reared on medium supplemented with ethanol and two reared on standard medium, were electrophoretically monitored for 28 generations. During the first 12 generations, allelic, genotypic and gametic frequencies were determined for eight polymorphic enzymes: GOT, alpha-GPDH, MDH, ADH, TO, E6, Ec and ODH. Samples from generation 18 and 28 were electrophoretically typed for ADH and alpha-GPDH. In addition, samples from generation 27 were analyzed for the presence of inversion heterozygotes. The experimental results showed rapid gene-frequency divergence between control and treatment populations at the Adh locus in a direction consistent with the activity hierarchy of Adh genotypes. Gene-frequency divergence between control and treatment populations also occurred at the alpha-Gpdh locus, although the agreement among replicates appeared to have broken down by generation 28. No differential gene-frequency change occurred at any of the six remaining marker loci. Furthermore, values of linkage disequilibria among all linked pairs of genes were initially small and remained small throughout the course of the experiment. Taking these facts into account, it is argued that the gene-frequency response observed at ADH is most probably caused by selection at the Adh locus. The gene frequency response at alpha-Gpdh can also be be accounted for in terms of the effect of ethanol on energy metabolism, although other explanations cannot be excluded.

Cytogenetic Analysis of Chromosome 3 in DROSOPHILA MELANOGASTER: Isolation and Characterization of Four New Alleles of the Proboscipedia (pb) Locus.

Abstract: Previous studies on proximal 3R have cytologically localized the dominant homeotic loci Antennapedia (Antp), Multiple Sex Comb (Msc), Nasobemia (Ns), and Extra Sex Comb (Scx). In this study we set out to find the site of the proboscipedia (pb) locus. In order to accomplish this, four new alleles of this homeotic gene were induced with gamma rays. Genetic and cytogenetic analyses have shown that the pb locus resides in polytene chromosome bands 84A1–6, immediately adjacent to the Antp gene complex in 84B1–2. An analysis of the morphology of the proboscis and the dose relationships of the four new alleles have shown that this homeosis is unusual in at least two respects. First, the two different developmental fates realized in the proboscis at 18° (labial palps → arista) and 29° (labial palps → leg) under the influence of pb1 grown at 18°, while the remaining three are like pb1 at 29°. Dosage studies reveal that this difference reflects a hypomorphic vs. amorphic condition. Second, like the original, these new alleles produce a prothoracic rather than a mesothoracic leg in the proboscis. Both of these results indicate that pb is unique among the homeotics, and as such it may offer some new insights into developmental processes.

Inversions fail to account for allozyme clines.

Abstract: Allozyme and inversion data from natural populations of Drosophila melanogaster from the eastern United States were analyzed to determine whether the clines at allozyme loci are due to nonrandom associations with common cosmopolitan inversions. All inversions show strong clines. Clines were large and significant for half of the eight allozyme loci. An analysis of the contribution of inversions to clines of allozyme genes revealed three outcomes: the inversion cline (1) enhanced the allozyme cline, but was only partly responsible, (2) reduced the allozyme cline, and (3) had no effect. The allozyme clines were mainly determined by the pattern of allele frequencies within the chromosomal arrangements. Consequently, it was concluded that allozyme clines would exist in the absence of inversion clines.

Characterization of a mutation in yeast causing nonrandom chromosome loss during mitosis.

Abstract: Diploid strains of the yeast Saccharomyces cerevisiae homozygous for a recessive chromosome loss mutation ( chl ) exhibit a high degree of mitotic instability. Cells become monosomic for chromosome III at a frequency of approximately one percent of all cell divisions. Chromosome loss at this high frequency is also found for chromosome I , and at lesser frequencies for chromosomes VIII and XVI . In contrast, little or no chromosome loss is found for six other linkage groups tested ( II, V, VI, VII, XI and XVII ). The chl mutation also induces a ten-fold increase in both intergenic and intragenic mitotic recombination on all ten linkage groups tested. The chl mutation does not cause an increase in spontaneous mutations, nor are mutant strains sensitive to UV or γ irradiation. The effects of chl during meiosis are observed primarily in reduced spore viability. A decrease in chromosome III linkage relationships is also found.

Statistical Studies on Protein Polymorphism in Natural Populations II. Gene Differentiation between Populations.

Abstract: With the aim of testing the validity of the mutation-drift hypothesis, we examined the pattern of genetic differentiation between populations by using data from Drosophila, fishes, reptiles, and mammals. The observed relationship between genetic identity and correlation of heterozygosities of different populations or species was generally in good agreement with the theoretical expectations from the mutation-drift theory, when the variation in mutation rate among loci was taken into account. In some species of Drosophila, however, the correlation was unduly high. The relationship between the mean and variance of genetic distance was also in good agreement with the theoretical prediction in almost all organisms. We noted that both the distribution of heterozygosity within species and the pattern of genetic differentiation between species can be explained by the same set of genetic parameters in each group of organisms. Alternative hypotheses for explaining these observations are discussed.

MUTATIONS OF THE a MATING-TYPE GENE IN NEUROSPORA CRASSA

Abstract: In Neurospora, the mating-type locus controls both mating ( A + a is fertile) and heterokaryosis (A + a is incompatible). The two alleles appear stable: no novel fertility reactions have ever been reported, and attempts to separate fertility and heterokaryon incompatibility functions by recombination have been unsuccessful. In the present approach the locus was studied through a mutational analysis of heterokaryon incompatibility function. A selection system was used that detects vigorous (A + a) heterokaryotic colonies against a background of inhibited growth. Twenty-five mutants of an a strain were produced following mutagenic treatment with UV and NG: 15 were viable as homokaryons and 10 were not. All but one were infertile, but most showed an abortive mating reaction involving the production of barren, well-developed perithecia with A and (surprisingly) a testers. None of the mutants complement each other to restore fertility. Seven mutants have been mapped to the mating-type locus region of chromosome 1. Restoration of fertility was used to detect revertants, and these were found in five out of the eight mutants tested. (A dose response was observed). In four cases incompatibility was fully restored and in one case it was not.—The results suggest two positive actions of the locus when in heterozygous (A/a) combination (the stimulation of some stage of ascus production and the inhibition of vegetative heterokaryosis), and one positive action in homozygous combination (the production of a perithecial inhibitor).

Gene duplication in Saccharomyces cerevisiae.

Abstract: Five indepdendent duplications of the acid-phosphatase (aphtase) structural gene (acp1) were recovered from chemostat populations of S. cerevisiae that were subject to selection for in vivo hyper-aphtase activity. Two of the duplications arose spontaneously. Three of them were induced by UV. All five of the duplication events involved the transpositioning of the aphtase structural gene, acp1, and all known genes distal to acp1 on the right arm of chromosome II, to the terminus of an arm of other unknown chromosomes. One of the five duplicated regions of the right arm of chromosome II was found to be transmitted mitotically and meiotically with very high fidelity. The other four duplicated regions of the right arm of chromosome II were found to be unstable, being lost at a rate of about 2% per mitosis. However, selection for increased fidelity of mitotic transmission was effective in one of these strains. No tandem duplications of the aphtase structural gene were found.