bluuebunny/crossref_metadata_2025 huggingface dataset:
Transvection in the iab-5,6,7 region of the bithorax complex of Drosophila: homology independent interactions in trans.
Authors: Hopmann R , Duncan D , Duncan I
Published: January 2021

The Abdominal-B (Abd-B) gene of the bithorax complex (BX-C) of Drosophila controls the identities of the fifth through seventh abdominal segments and segments in the genitalia (more precisely, parasegments 10-14). Here we focus on iab-5, iab-6 and iab-7, regulatory regions of Abd-B that control expression in the fifth, sixth and seventh abdominal segments (parasegments 10-12). By analysis of partial BX-C deficiencies, we show that these regions are able to promote fifth and sixth abdominal segment identities in the absence of an Abd-B gene in cis. We establish that this ability does not result from cis-regulation of the adjacent abd-A or Ubx genes of the BX-C but rather occurs because the iab-5,6,7 region is able to interact with Abd-B in trans. We demonstrate that this interaction is proximity dependent and is, therefore, a case of what E. B. Lewis has called transvection. Interactions of this type are presumably facilitated by the synapsis of homologues that occurs in somatic cells of Dipterans. Although transvection has been detected in a number of Drosophila genes, transvection of the iab-5,6,7 region is exceptional in two ways. First, interaction in trans with Abd-B does not require that homologues share homologous sequences within, or for some distance to either side of, the BX-C. This is the first case of transvection shown to be independent of local synapsis. A second unusual feature of iab-5,6,7 transvection is that it is remarkably difficult to disrupt by heterozygosity for chromosome rearrangements. The lack of requirement for local synapsis and the tenacity of trans-interaction argue that the iab-5,6,7 region can locate and interact with Abd-B over considerable distance. This is consistent with the normal role of iab-5,6,7, which must act over some 20-60 kb to influence its regulatory target in cis at the Abd-B promoter. Evidence is presented that trans-action of iab-5,6,7 requires, and may be mediated by, the region between distal iab-7 and Abd-B. Also, we show that iab-5,6,7 transvection is independent of the allelic state of zeste, a gene that influences several other cases of transvection. The long-range nature of interactions in trans between iab-5,6,7 and Abd-B suggests that similar interactions could operate effectively in organisms lacking extensive somatic pairing. Transvection may, therefore, be of more general significance than previously suspected.
Polygenic mutation in Drosophila melanogaster: the causal relationship of bristle number to fitness.
Authors: Nuzhdin S V , Fry J D , Mackay T F
Published: January 2021

The association between sternopleural and abdominal bristle number and fitness in Drosophila melanogaster was determined for sublines of an initially highly inbred strain that were maintained by divergent artificial selection for 150 generations or by random mating for 180 generations. Replicate selection lines had more extreme bristle numbers than those that were maintained without artificial selection at the same census size for approximately the same number of generations. The average fitness, estimated by a single generation of competition against a compound autosome strain, was 0.17 for lines selected for high and low abdominal bristle numbers and 0.19 for lines selected for high and low sternopleural bristle number. The average fitness of unselected lines, 0.46, was significantly higher than that of the selection lines. The fitnesses and the relationships of bristle number to fitness in progeny of all possible crosses of high x high (H x H), high x low (H x L) and low x low (L x L) selection lines were examined to determine whether the observed intermediate optima were caused by direct stabilizing selection on bristle number or by apparent stabilizing selection mediated through deleterious pleiotropic fitness effects of mutations affecting bristle number. Although bristle number was nearly additive for progeny of H x H, H x L and L x L crosses among sternopleural bristle selection lines, their mean fitnesses were not significantly different from each other, or from the mean fitness of the unselected lines, suggesting partly or completely recessive pleiotropic fitness effects cause apparent stabilizing selection. The average fitness of the progeny of H x H abdominal bristle selection lines was not significantly different from the fitness of unselected lines, but the mean fitness of the progeny of L x L crosses was not significantly different from that of the pure low lines. This is consistent with direct selection against low but not high abdominal bristle number, but the interpretation is confounded by variation in average degree of dominance for fitness (on average recessive in the high abdominal bristle selection lines and additive in the low abdominal bristle selection lines). Neither direct stabilizing selection nor pleiotropy, therefore, can account for all the observations.
Mus spretus LINE-1 sequences detected in the Mus musculus inbred strain C57BL/6J using LINE-1 DNA probes.
Authors: Rikke B A , Zhao Y , Daggett L P , Reyes R , Hardies S C
Published: January 2021

The inbred mouse strain, C57BL/6J, was derived from mice of the Mus musculus complex. C57BL/6J can be crossed in the laboratory with a closely related mouse species, M. spretus to produce fertile offspring; however there has been no previous evidence of gene flow between M. spretus and M. musculus in nature. Analysis of the repetitive sequence LINE-1, using both direct sequence analysis and genomic Southern blot hybridization to species-specific LINE-1 hybridization probes, demonstrates the presence of LINE-1 elements in C57BL/6J that were derived from the species M. spretus. These spretus-like LINE-1 elements in C57BL/6J reveal a cross to M. spretus somewhere in the history of C57BL/6J. It is unclear if the spretus-like LINE-1 elements are still embedded in flanking DNA derived from M. spretus or if they have transposed to new sites. The number of spretus-like elements detected suggests a maximum of 6.5% of the C57BL/6J genome may be derived from M. spretus.
A space-time process model for the evolution of DNA sequences.
Authors: Yang Z
Published: January 2021

We describe a model for the evolution of DNA sequences by nucleotide substitution, whereby nucleotide sites in the sequence evolve over time, whereas the rates of substitution are variable and correlated over sites. The temporal process used to describe substitutions between nucleotides is a continuous-time Markov process, with the four nucleotides as the states. The spatial process used to describe variation and dependence of substitution rates over sites is based on a serially correlated gamma distribution, i.e., an auto-gamma model assuming Markov-dependence of rates at adjacent sites. To achieve computational efficiency, we use several equal-probability categories to approximate the gamma distribution, and the result is an auto-discrete-gamma model for rates over sites. Correlation of rates at sites then is modeled by the Markov chain transition of rates at adjacent sites from one rate category to another, the states of the chain being the rate categories. Two versions of nonparametric models, which place no restrictions on the distributional forms of rates for sites, also are considered, assuming either independence or Markov dependence. The models are applied to data of a segment of mitochondrial genome from nine primate species. Model parameters are estimated by the maximum likelihood method, and models are compared by the likelihood ratio test. Tremendous variation of rates among sites in the sequence is revealed by the analyses, and when rate differences for different codon positions are appropriately accounted for in the models, substitution rates at adjacent sites are found to be strongly (positively) correlated. Robustness of the results to uncertainty of the phylogenetic tree linking the species is examined.
Meiotic instability of Pythium sylvaticum as demonstrated by inheritance of nuclear markers and karyotype analysis.
Authors: Martin F
Published: January 2021

Progeny from a sexual outcross between opposite mating types of Pythium sylvaticum were analyzed for inheritance of RFLP and random amplified polymorphic DNA (RAPD) markers. Although most were inherited in expected Mendelian frequencies, several were not. Pulsed field gel electrophoresis was employed to examine these unexpected patterns of marker inheritance at a karyotypic level. Parental oogonial and antheridial isolates had different electrophoretic karyotypes and minimum number of chromosome-sized DNAs (13 and 12, respectively), however, summation of the sizes of all chromosomal bands for each isolate was similar at approximately 37 Mb. Progeny karyotypes differed significantly from each other and the parental isolates, ranging in estimated minimum number of chromosome-sized DNAs from 9 to 13 and the summation of band sizes within each isolate from 28.1 to 39.0 Mb. For the eight isolates most extensively analyzed, 80% of the progeny chromosome-sized DNAs were nonparental in size or hybridization grouping of cDNA clones and isolated RAPD markers. Based on the results of Southern analysis it appears that length mutations and perhaps aneuploidy and translocations have contributed to generation of karyotypic polymorphisms. Nineteen field isolates of P. sylvaticum collected from the same location also exhibited significantly different karyotypes, suggesting that the meiotic instability observed in the laboratory also is occurring in field populations.
Linkage map of the honey bee, Apis mellifera, based on RAPD markers.
Authors: Hunt G J , Page R E
Published: January 2021

A linkage map was constructed for the honey bee based on the segregation of 365 random amplified polymorphic DNA (RAPD) markers in haploid male progeny of a single female bee. The X locus for sex determination and genes for black body color and malate dehydrogenase were mapped to separate linkage groups. RAPD markers were very efficient for mapping, with an average of about 2.8 loci mapped for each 10-nucleotide primer that was used in polymerase chain reactions. The mean interval size between markers on the map was 9.1 cM. The map covered 3110 cM of linked markers on 26 linkage groups. We estimate the total genome size to be approximately 3450 cM. The size of the map indicated a very high recombination rate for the honey bee. The relationship of physical to genetic distance was estimated at 52 kb/cM, suggesting that map-based cloning of genes will be feasible for this species.
Molecular evolution of the Ac/Ds transposable-element family in pearl millet and other grasses.
Authors: Huttley G A , MacRae A F , Clegg M T
Published: January 2021

We report an Ac-like sequence from pearl millet (Pennisetum glaucum) and deletion derivative Ac-like sequences from pearl millet and another grass species, Bambusa multiplex. Sequence relationships between the pearl millet and maize Ac elements suggest that Ac/Ds transposable-element family is ancient. Further, the sequence identity between the Bambusa Ac-like sequence and maize Ac implies that the Ac/Ds transposable-element family has been in the grass family since its inception. The Ac-like sequences reported from pearl millet and maize Ac are statistically heterogeneous in pair-wise distance comparisons to each other. Yet, we are unable to discriminate between differential selection or ectopic exchange (recombination and conversion) between nonidentical transposable element homologues, as the cause of the heterogeneity. However, the more extreme heterogeneity exhibited between the previously described pearl millet element and maize Ac seems likely to derive from ectopic exchange between elements with different levels of divergence.
A nonparametric approach for mapping quantitative trait loci.
Authors: Kruglyak L , Lander E S
Published: January 2021

Genetic mapping of quantitative trait loci (QTLs) is performed typically by using a parametric approach, based on the assumption that the phenotype follows a normal distribution. Many traits of interest, however, are not normally distributed. In this paper, we present a nonparametric approach to QTL mapping applicable to any phenotypic distribution. The method is based on a statistic ZW, which generalizes the nonparametric Wilcoxon rank-sum test to the situation of whole-genome search by interval mapping. We determine the appropriate significance level for the statistic ZW, by showing that its asymptotic null distribution follows an Ornstein-Uhlenbeck process. These results provide a robust, distribution-free method for mapping QTLs.
Somatic mutation favors the evolution of diploidy.
Authors: Orr H A
Published: January 2021

Explanation of diploidy have focused on advantages gained from masking deleterious mutations that are inherited. Recent theory has shown that these explanations are flawed. Indeed, we still lack any satisfactory explanation of diploidy in species that are asexual or that recombine only rarely. Here I consider a possibility first suggested by Efroimson in 1932, by Muller in 1964 and by Crow and Kimura in 1965: diploidy may provide protection against somatic, not inherited, mutations. I both compare the mean fitness of haploid and diploid populations that are asexual and investigate the invasion of "diploidy" alleles in sexual populations. When deleterious mutations are partially recessive and somatic mutation is sufficiently common, somatic mutation provides a clear advantage to diploidy in both asexual and sexual species.
Hypomorphic mutations in the larval photokinesis A (lphA) gene have stage-specific effects on visual system function in Drosophila melanogaster.
Authors: Gordesky-Gold B , Warrick J M , Bixler A , Beasley J E , Tompkins L
Published: January 2021

Of the many genes that are expressed in the visual system of Drosophila melanogaster adults, some affect larval vision. However, with the exception of one X-linked mutation, no genes that have larval-specific effects on visual system structure or function have previously been reported. We describe the isolation and characterization of two mutant alleles that define the larval photokinesis A (lphA) gene, one allele of which is associated with a P-element insertion at cytogenetic locus 8E1-10. Larvae that express lphA mutations are, like normal animals, negatively photokinetic, but they are less responsive to white light than lphA + controls. Larvae that are heterozygous in trans for a mutant lphA allele and a deficiency that uncovers the lphA locus are blind, which indicates that the mutant allele is hypomorphic. lphA larvae respond normally to odorants and taste stimuli. Moreover, the lphA mutations do not affect adult flies' fast phototaxis or visually driven aspects of male sexual behavior, and electroretinograms recorded from the compound eyes of lphA/deficiency heterozygotes and lphA1/lphA2 females are normal. These observations suggest that the lphA gene affects a larval-specific aspect of visual system function.
P-element mutations affecting embryonic peripheral nervous system development in Drosophila melanogaster.
Authors: Kania A , Salzberg A , Bhat M , D'Evelyn D , He Y , Kiss I , Bellen H J
Published: January 2021

The Drosophila embryonic peripheral nervous system (PNS) is an excellent model system to study the molecular mechanisms governing neural development. To identify genes controlling PNS development, we screened 2000 lethal P-element insertion strains. The PNS of mutant embryos was examined using the neural specific marker MAb 22C10, and 92 mutant strains were retained for further analysis. Genetic and cytological analysis of these strains shows that 42 mutations affect previously isolated genes that are known to be required for PNS development: longitudinals lacking (19), mastermind (15), numb (4), big brain (2), and spitz (2). The remaining 50 mutations were classified into 29 complementation groups and the P-element insertions were cytologically mapped. The mutants were classified in five major classes on the basis of their phenotype: gain of neurons, loss of neurons, organizational defects, pathfinding defects and morphological defects. Herein we report the preliminary phenotypic characterization of each of these complementation groups as well as the embryonic lacZ expression pattern of each P-element strain. Our analysis indicates that in most of the P-element insertion strains, the lacZ reporter gene is not expressed in the developing PNS.
Half-tetrad analysis in zebrafish: mapping the ros mutation and the centromere of linkage group I.
Authors: Johnson S L , Africa D , Horne S , Postlethwait J H
Published: January 2021

Analysis of meiotic tetrads is routinely used to determine genetic linkage in various fungi. Here we apply tetrad analysis to the study of genetic linkage in a vertebrate. The half-tetrad genotypes of gynogenetic diploid zebrafish produced by early-pressure (EP) treatment were used to investigate the linkage relationships of two recessive pigment pattern mutations, leopard (leo) and rose (ros). The results showed that ros is tightly linked to its centromere and leo maps 31 cM from its centromere. Analysis of half-tetrads segregating for ros and leo in repulsion revealed no homozygous ros individuals among 32 homozygous leo half-tetrads--i.e., a parental ditype (PD) to nonparental ditype (NPD) ratio of 32:0. This result shows that ros is linked to leo, a mutation previously mapped to Linkage Group I. Investigation of PCR-based DNA polymorphisms on Linkage Group I confirmed the location of ros near the centromere of this linkage group. We propose an efficient, generally useful method to assign new mutations to a linkage group in zebrafish by determining which of 25 polymerase chain reaction (PCR)-based centromere markers shows a significant excess of PD to NPD in half-tetrad fish.
Genetics of male sterility in gynodioecious Plantago coronopus. I. Cytoplasmic variation.
Authors: Koelewijn H P , Van Damme J M
Published: January 2021

Inheritance of male sterility was studied in the gynodioecious species Plantago coronopus using five plants and their descendants from an area of approximately 50 m2 in each of six locations. The crosses were planned to test for cytoplasmic inheritance of male sterility. In four locations significant differences between reciprocal crosses were observed. The progenies of these reciprocal crosses were used in a crossing scheme designed to test whether these reciprocal differences were caused by different cytoplasmic types between the plants. In all four locations, the existence of at least two cytoplasmic types could be shown. Moreover, the results of the crosses between locations showed that the same two cytoplasmic types were present in all four locations. We therefore argue that there is only limited cytoplasmic variation in P. coronopus. In each cytoplasmic type a series of intermediate sex forms occurred. A marked difference in restoration level existed between the two cytoplasmic types. Plants with cytoplasmic type 2 hardly segregated male steriles, in contrast to plants with cytoplasmic type 1.
Suppression of a new allele of the yeast RAD52 gene by overexpression of RAD51, mutations in srs2 and ccr4, or mating-type heterozygosity.
Authors: Schild D
Published: January 2021

The RAD52 gene of Saccharomyces cerevisiae is involved both in the recombinational repair of DNA damage and in mitotic and meiotic recombination. A new allele of rad52 has been isolated that has unusual properties. Unlike other alleles of rad52, this allele (rad52-20) is partially suppressed by an srs2 deletion; srs2 mutations normally act to suppress only rad6 and rad18 mutations. In addition, although haploid rad52-20 strains are very X-ray sensitive, diploids homozygous for this allele are only slightly X-ray sensitive and undergo normal meiosis and meiotic recombination. Because rad52-20 diploids homozygous for mating type are very X-ray sensitive, mating-type heterozygosity is acting to suppress rad52-20. Mating-type heterozygosity suppresses this allele even in haploids, because sir mutations, which result in expression of the normally silent mating-type cassettes, were identified among the extragenic revertants of rad52-20. A new allele of srs2 and alleles of the transcriptional regulatory genes ccr4 and caf1 were among the other extragenic revertants of rad52-20. Because other researchers have shown that the RAD51 and RAD52 proteins interact, RAD51 on a high copy number plasmid was tested and found to suppress the rad52-20 allele, but RAD54, 55 and 57 did not suppress. The RAD51 plasmid did not suppress rad52-1. The rad52-20 allele may encode a protein that has low affinity binding to the RAD51 protein. To test whether the selected revertants suppressed rad52-20 by elevating the expression of RAD51, an integrated RAD51-lacZ fusion was genetically crossed into each revertant. Because none of the revertants increased the level of RAD51-lacZ, the revertants must exert their effect by one or more mechanisms that are not mediated by RAD51.
Molecular genetic characterization of six recessive viable alleles of the mouse agouti locus.
Authors: Hustad C M , Perry W L , Siracusa L D , Rasberry C , Cobb L , Cattanach B M , Kovatch R , Copeland N G , Jenkins N A
Published: January 2021

The agouti locus on mouse chromosome 2 encodes a secreted cysteine-rich protein of 131 amino acids that acts as a molecular switch to instruct the melanocyte to make either yellow pigment (phaeomelanin) or black pigment (eumelanin). Mutations that up-regulate agouti expression are dominant to those causing decreased expression and result in yellow coat color. Other associated effects are obesity, diabetes, and increased susceptibility to tumors. To try to define important functional domains of the agouti protein, we have analyzed the molecular defects present in a series of recessive viable agouti mutations. In total, six alleles (amJ, au, ada, a16H, a18H, ae) were examined at both the RNA and DNA level. Two of the alleles, a16H and ae, result from mutations in the agouti coding region. Four alleles (amJ, au, a18H, and ada) appear to represent regulatory mutations that down-regulate agouti expression. Interestingly, one of these mutations, a18H, also appears to cause an immunological defect in the homozygous condition. This immunological defect is somewhat analogous to that observed in motheaten (me) mutant mice. Short and long-range restriction enzyme analyses of homozygous a18H DNA are consistent with the hypothesis that a18H results from a paracentric inversion where one end of the inversion maps in the 5' regulatory region of agouti and the other end in or near a gene that is required for normal immunological function. Cloning the breakpoints of this putative inversion should allow us to identify the gene that confers this interesting immunological disorder.
Mu1-related transposable elements of maize preferentially insert into low copy number DNA.
Authors: Cresse A D , Hulbert S H , Brown W E , Lucas J R , Bennetzen J L
Published: January 2021

The Mutator transposable element system of maize was originally identified through its induction of mutations at an exceptionally high frequency and at a wide variety of loci. The Mu1 subfamily of transposable elements within this system are responsible for the majority of Mutator-induced mutations. Mu 1-related elements were isolated from active Mutator plants and their flanking DNA was characterized. Sequence analyses revealed perfect nine base target duplications directly flanking the insert for 13 of the 14 elements studied. Hybridizational studies indicated that Mu1-like elements insert primarily into regions of the maize genome that are of low copy number. This preferential selection of low copy number DNA as targets for Mu element insertion was not directed by any specific secondary structure(s) that could be detected in this study, but the 9-bp target duplications exhibited a discernibly higher than random match with the consensus sequence 5'-G-T-T-G-G/C-A-G-G/A-G-3'.
Spatial structure of two-locus genotypes under isolation by distance.
Authors: Epperson B K
Published: January 2021

Extensive Monte Carlo simulations are conducted of spatial distributions of two-locus genotypes in large, continuous populations under isolation by distance models. The results show that substantial patches of double homozygotes are present in the spatial structures, even when loci are unlinked. The stochastic spread of identical two-locus genotypes largely outpowers the tendency for recombination to decouple patterns for separate loci. A spatial patch is a large area containing mostly one double homozygous genotype in a highly contiguous constellation. This patch structure is reflected in high positive spatial autocorrelations and large excesses of pairs, or joins, of identical double homozygotes at short-to-intermediate distances of spatial separation. Although spatial patches of double homozygotes are the dominant spatial feature, and the major contributors to overall high levels of autocorrelations among two-locus genotypes, other substantial features include areas of concentrations of identical genotypes heterozygous at only one locus. One implication of the patch structure is the presence of high levels of linkage disequilibrium, caused by isolation by distance even for unlinked loci, at some spatial scales; yet the disequilibrium in the large total populations is near 0. Thus linkage disequilibrium produced by isolation by distance is highly dependent on spatial scale. Another implication is that high degrees of spatial structuring and autocorrelations are produced for genetic variation controlling quantitative traits, at least when the number of loci is relatively small, under a wide range of situations, even if the trait is selectively neutral. The significance of the results to field studies is also examined.
Hot spots of recombination in fission yeast: inactivation of the M26 hot spot by deletion of the ade6 promoter and the novel hotspot ura4-aim.
Authors: Zahn-Zabal M , Lehmann E , Kohli J
Published: January 2021

The M26 mutation in the ade6 gene of Schizosaccharomyces pombe creates a hot spot of meiotic recombination. A single base substitution, the M26 mutation is situated within the open reading frame, near the 5' end. It has previously been shown that the heptanucleotide sequence 5' ATGACGT 3', which includes the M26 mutation, is required for hot spot activity. The 510-bp ade6-delXB deletion encompasses the promoter and the first 23 bp of the open reading frame, ending 112 bp upstream of M26. Deletion of the promoter in cis to M26 abolishes hot spot activity, while deletion in trans to M26 has no effect. Homozygous deletion of the promoter also eliminates M26 hot spot activity, indicating that the heterology created through deletion of the promoter per se is not responsible for the loss of hot spot activity. Thus, DNA sequences other than the heptanucleotide 5' ATGACGT 3', which must be located at the 5' end of the ade6 gene, appear to be required for hot spot activity. While the M26 hotspot stimulates crossovers associated with M26 conversion, it does not affect the crossover frequency in the intervals adjacent to ade6. The flanking marker ura4-aim, a heterology created by insertion of the ura4+ gene upstream of ade6, turned out to be a hot spot itself. It shows disparity of conversion with preferential loss of the insertion. The frequency of conversion at ura4-aim is reduced when the M26 hot spot is active 15 kb away, indicating competition for recombination factors by hot spots in close proximity.
Caenorhabditis elegans mutants resistant to inhibitors of acetylcholinesterase.
Authors: Nguyen M , Alfonso A , Johnson C D , Rand J B
Published: January 2021

We characterized 18 genes from Caenorhabditis elegans that, when mutated, confer recessive resistance to inhibitors of acetylcholinesterase. These include previously described genes as well as newly identified genes; they encode essential as well as nonessential functions. In the absence of acetylcholinesterase inhibitors, the different mutants display a wide range of behavioral deficits, from mild uncoordination to almost complete paralysis. Measurements of acetylcholine levels in these mutants suggest that some of the genes are involved in presynaptic functions.
Temporal patterns of gene expression in the antenna of the adult Drosophila melanogaster.
Authors: Helfand S L , Blake K J , Rogina B , Stracks M D , Centurion A , Naprta B
Published: January 2021

The time course of gene expression in the adult fruit fly has been partially characterized by using enhancer trap and reporter gene constructs that mark 49 different genes. The relative intensity of the reporter protein in individual cells of the antennae was measured as a function of adult age. Most genes showed a graduated expression, and the intensity of expression had a reproducible and characteristic time course. Different genes displayed different temporal patterns of expression and more often than not the pattern of expression was complex. We found a number of genes having patterns that scaled with life span. In these cases the intensity of gene expression was found to be invariant with respect to biological time, when expressed as a fraction of the life span of the line. The scaling was observed even when life span was varied as much as threefold. Such scaling serves to (1) further demonstrate that deterministic mechanisms such as gene regulation act to generate the temporal patterns of expression seen during adult life, (2) indicate that control of these regulatory mechanisms is linked to life span, and (3) suggest mechanisms by which this control is accomplished. We have concluded that gene expression in the adult fly is often regulated in a fashion that allows for graduated expression over time, and that the regulation itself is changing throughout adult life according to some prescribed program or algorithm.
Effects of a transposable element insertion on alcohol dehydrogenase expression in Drosophila melanogaster.
Authors: Dunn R C , Laurie C C
Published: January 2021

Variation in the DNA sequence and level of alcohol dehydrogenase (Adh) gene expression in Drosophila melanogaster have been studied to determine what types of DNA polymorphisms contribute to phenotypic variation in natural populations. The Adh gene, like many others, shows a high level of variability in both DNA sequence and quantitative level of expression. A number of transposable element insertions occur in the Adh region and one of these, a copia insertion in the 5' flanking region, is associated with unusually low Adh expression. To determine whether this insertion (called R142) causes the low expression level, the insertion was excised from the cloned R142 Adh gene and the effect was assessed by P-element transformation. Removal of this insertion causes a threefold increase in the level of ADH, clearly showing that it contributes to the naturally occurring variation in expression at this locus. Removal of all but one LTR also causes a threefold increase, indicating that the mechanism is not a simple sequence disruption. Furthermore, this copia insertion, which is located between the two Adh promoters and their upstream enhancer sequences, has differential effects on the levels of proximal and distal transcripts. Finally, a test for the possible modifying effects of two suppressor loci, su(wa) and su(f), on this insertional mutation was negative, in contrast to a previous report in the literature.
Population structure of morphological traits in Clarkia dudleyana. I. Comparison of FST between allozymes and morphological traits.
Authors: Podolsky R H , Holtsford T P
Published: January 2021

Studies of genetic variation at allozyme loci, assumed to be selectively neutral, have provided valuable insights into the genetic structure of numerous populations. The degree to which population structure of allozyme variation reflects that of quantitative traits, however, is not well resolved. Here, we compare estimates of population differentiation (FST) of 11 populations for allozymes with those for nine discrete and nine continuous morphological traits. Overall, the allozymes have the lowest FST estimates, indicating relatively little population differentiation. Excepting two traits, petal width and long internode length, the continuous morphological traits have estimates similar to those from allozymes. The discrete morphological traits tend to have the highest estimates. On a single trait basis, estimates of FST for four discrete and two continuous traits are higher than those for allozymes. A more detailed (narrow-sense quantitative) genetic study of two populations suggests that these estimates of FST may underestimate the true value because of dominance. Clustering analyses show that the pattern of differentiation for the discrete morphological traits strongly reflects the geographical distribution of the populations, whereas the patterns for the continuous traits and allozymes do not. These results suggest that selection has been occurring on the discrete morphological traits, selecting toward a common optimum within each geographic group, and optima differing among geographic groups.
Statistical methods for linkage analysis of complex traits from high-resolution maps of identity by descent.
Authors: Dupuis J , Brown P O , Siegmund D
Published: January 2021

A multilocus model for complex traits is described that generalizes the additive and multiplicative models and hence allows simultaneously for both heterogeneity and gene interaction (epistasis). Statistical methods of linkage analysis are discussed under the assumption that identity by descent data from a dense set of polymorphic markers are available. Three methods, single locus search, simultaneous search and conditional search, are described and compared.
Species-specific and mating type-specific DNA regions adjacent to mating type idiomorphs in the genus Neurospora.
Authors: Randall T A , Metzenberg R L
Published: January 2021

Mating type idiomorphs control mating and subsequent sexual development in Neurospora crassa and were previously shown to be well conserved in other Neurospora species. The centromere-proximal flanks of the A and a idiomorphs, but not the distal flanks from representative heterothallic, pseudohomothallic, and homothallic Neurospora species contain apparent species-specific and/or mating type-specific sequences adjacent to the well-conserved idiomorphs. The variable flank is bordered by regions that are highly homologous in all species. The sequence of approximately 1 kb immediately flanking the conserved idiomorphs of each species was determined. Sequence identity between species ranged from 20% (essentially unrelated) to > 90%. By contrast, the mt-A1 gene shows 88-98% identity. Sequence and hybridization data also show that the centromere-proximal flanks are very different between the two mating types for N. intermedia, N. discreta, and N. tetrasperma, but not for N. sitophila and N. crassa. The data suggest a close evolutionary relationship between several of the species; this is suppported by phylogenetic analysis of their respective mt-A1 genes. The origin of the variable regions adjacent to the evolutionarily conserved mating type idiomorphs is unknown.
Molecular evolution of the duplicated Amy locus in the Drosophila melanogaster species subgroup: concerted evolution only in the coding region and an excess of nonsynonymous substitutions in speciation.
Authors: Shibata H , Yamazaki T
Published: January 2021

From the analysis of restriction maps of the Amy region in eight sibling species belonging to the Drosophila melanogaster species subgroup, we herein show that the patterns of duplication of the Amy gene are almost the same in all species. This indicates that duplication occurred before speciation within this species subgroup. From the nucleotide sequence data, we show a strong within-species similarity between the duplicated loci in the Amy coding region. This is in contrast to a strong similarity in the 5' and 3' flanking regions within each locus (proximal or distal) throughout the species subgroup. This means that concerted evolution occurred only in the Amy coding region and that differentiated evolution between the duplication occurred in the flanking regions. Moreover, when comparing the species, we also found a significant excess of nonsynonymous substitutions. In particular, all the fixed substitutions specific to D. erecta were found to be nonsynonymous. We thus conclude that adaptive protein evolution occurred in the lineage of D. erecta that is a "specialist" species for host plants and probably also occurs in the process of speciation in general.
Complete sequence of the mitochondrial DNA of the annelid worm Lumbricus terrestris.
Authors: Boore J L , Brown W M
Published: January 2021

We have determined the complete nucleotide (nt) sequence of the mitochondrial genome of an oligochaete annelid, the earthworm Lumbricus terrestris. This genome contains the 37 genes typical of metazoan mitochondrial DNA (mtDNA), including ATPase8, which is missing from some invertebrate mtDNAs. ATPase8 is not immediately upstream of ATPase6, a condition found previously only in the mtDNA of snails. All genes are transcribed from the same DNA strand. The largest noncoding region is 384 nt and is characterized by several homopolymer runs, a tract of alternating TA pairs, and potential secondary structures. All protein-encoding genes either overlap the adjacent downstream gene or end at an abbreviated stop codon. In Lumbricus mitochondria, the variation of the genetic code that is typical of most invertebrate mitochondrial genomes is used. Only the codon ATG is used for translation initiation. Lumbricus mtDNA is A + T rich, which appears to affect the codon usage pattern. The DHU arm appears to be unpaired not only in tRNAser(AGN), as is typical for metazoans, but perhaps also in tRNAser(UCN), a condition found previously only in a chiton and among nematodes. Relating the Lumbricus gene organization to those of other major protostome groups requires numerous rearrangements.
Muller's ratchet, epistasis and mutation effects.
Authors: Butcher D
Published: January 2021

In this study, computer simulation is used to show that despite synergistic epistasis for fitness, Muller's ratchet can lead to lethal fitness loss in a population of asexuals through the accumulation of deleterious mutations. This result contradicts previous work that indicated that epistasis will halt the ratchet. The present results show that epistasis will not halt the ratchet provided that rather than a single deleterious mutation effect, there is a distribution of deleterious mutation effects with sufficient density near zero. In addition to epistasis and mutation distribution, the ability of Muller's ratchet to lead to the extinction of an asexual population under epistasis for fitness depends strongly on the expected number of offspring that survive to reproductive age. This strong dependence is not present in the nonepistatic model and suggests that interpreting the population growth parameter as fecundity is inadequate. Because a continuous distribution of mutation effects is used in this model, an emphasis is placed on the dynamics of the mutation effect distribution rather than on the dynamics of the number of least mutation loaded individuals. This perspective suggests that current models of gene interaction are too simple to apply directly to long-term prediction for populations undergoing the ratchet.
Genetic analysis of delta helD and delta uvrD mutations in combination with other genes in the RecF recombination pathway in Escherichia coli: suppression of a ruvB mutation by a uvrD deletion.
Authors: Mendonca V M , Matson S W
Published: January 2021

Helicase II (uvrD gene product) and helicase IV (helD gene product) have been shown previously to be involved in the RecF pathway of recombination. To better understand the role of these two proteins in homologous recombination in the RecF pathway [recBCsbcB(C) background, we investigated the interactions between helD, uvrD and the following RecF pathway genes: recF, recO, recN and ruvAB. We observed synergistic interactions between uvrD ant the recF, recN, recO and recG genes in both conjugational recombination and the repair of methylmethane sulfonate (MMS)-induced DNA damage. No synergistic interactions were detected between helD and the recF, recO and regN genes when conjugational recombination was analyzed. We did, however, detect synergistic interactions between helD and recF/recO in recombinational repair. Surprisingly, the uvrD deletion completely suppressed the phenotype of a ruvB mutation in a recBCsbcB(C) background. Both conjugational recombination efficiency and MMS-damaged DNA repair proficiency returned to wild-type levels in the deltauvrDruvB9 double mutant. Suppression of the effects of the ruvB mutation by a uvrD deletion was dependent on the recG and recN genes and not dependent on the recF/O/R genes. These data are discussed in the context of two "RecF" homologous recombination pathways operating in a recBCsbcB(C) strain background.
Spatial and temporal patterns of lin-12 expression during C. elegans hermaphrodite development.
Authors: Wilkinson H A , Greenwald I
Published: January 2021

The lin-12 gene encodes a receptor that mediates certain cell-cell interactions during Caenorhabditis elegans development. We have examined the expression of a lin-12::lacZ reporter gene in individual cells during the development of C. elegans hermaphrodites. lin-12::lacZ is expressed in a discrete spatial and temporal pattern during development and teh lin-12::lacZ reporter gene will provide a useful marker for other studies, particularly of somatic gonadal and vulval development. In general, the cells that express lin-12:: lacZ correspond to cells whose fates are known to be altered in lin-12 mutants implying that restriction of lin-12 expression may be an important regulatory mechanism; the exceptions to this statement may reveal the cellular defects that underlie aspects of the lin-12 phenotype that have not been previously explained. For decisions that are not naturally variable, lin-12::lacZ expression does not appear to change before or upon commitment to a cell fate implying that in these cases postranscriptional regulation of lin-12 activity may control cell fate specification.
Localization of the nic-7, ac-29 and thi-10 genes within the mating-type locus of Chlamydomonas reinhardtii.
Authors: Ferris P J
Published: January 2021

The tight linkage observed between the mating-type (mt) locus of Chlamydomonas reinhardtii and three auxotrophic mutations--nic-7 (nicotinamide-requiring), ac-29 (acetate-requiring), and thi-10 (thiamine-requiring)--has led to the hypothesis that recombination is suppressed in the mt region. The physical location of these three genes has been established by transformation with sets of cloned DNA from the mt region. They lie to the left and right of the highly rearranged (R) domain of the mt locus, which has been proposed to be responsible for teh recombinational suppression in the region. The cloned nic-7+ and thi-10+ genes will be useful as selectable markers for cotransformation markers for cotransformation experiments.
The Drosophila meiotic recombination gene mei-9 encodes a homologue of the yeast excision repair protein Rad1.
Authors: Sekelsky J J , McKim K S , Chin G M , Hawley R S
Published: January 2021

Meiotic recombination and DNA repair are mediated by overlapping sets of genes. In the yeast Saccharomyces cerevisiae, many genes required to repair DNA double-strand breaks are also required for meiotic recombination. In contrast, mutations in genes required for nucleotide excision repair (NER) have no detectable effects on meiotic recombination in S. cerevisiae. The Drosophila melanogaster mei-9 gene is unique among known recombination genes in that it is required for both meiotic recombination and NER. We have analyzed the mei-9 gene at the molecular level and found that it encodes a homologue of the S. cerevisiae excision repair protein Rad1, the probable homologue of mammalian XPF/ERCC4. Hence, the predominant process of meiotic recombination in Drosophila proceeds through a pathway that is at least partially distinct from that of S. cerevisiae, in that it requires an NER protein. The biochemical properties of the Rad1 protein allow us to explain the observation that mei-9 mutants suppress reciprocal exchange without suppressing the frequency of gene conversion.
The genetic and molecular organization of the Dopa decarboxylase gene cluster of Drosophila melanogaster.
Authors: Stathakis D G , Pentz E S , Freeman M E , Kullman J , Hankins G R , Pearlson N J , Wright T R
Published: January 2021

We report the complete molecular organization of the Dopa decarboxylase gene cluster. Mutagenesis screens recovered 77 new Df(2L)TW130 recessive lethal mutations. These new alleles combined with 263 previously isolated mutations in the cluster to define 18 essential genes. In addition, seven new deficiencies were isolated and characterized. Deficiency mapping, restriction fragment length polymorphism (RFLP) analysis and P-element-mediated germline transformation experiments determined the gene order for all 18 loci. Genomic and cDNA restriction endonuclease mapping, Northern blot analysis and DNA sequencing provided information on exact gene location, mRNA size and transcriptional direction for most of these loci. In addition, this analysis identified two transcription units that had not previously been identified by extensive mutagenesis screening. Most of the loci are contained within two dense subclusters. We discuss the effectiveness of mutagens and strategies used in our screens, the variable mutability of loci within the genome of Drosophila melanogaster, the cytological and molecular organization of the Ddc gene cluster, the validity of the one band-one gene hypothesis and a possible purpose for the clustering of genes in the Ddc region.
Nondisjunction rates and abnormal embryonic development in a mouse cross between heterozygotes carrying a (7, 18) robertsonian translocation chromosome.
Authors: Oakey R J , Matteson P G , Litwin S , Tilghman S M , Nussbaum R L
Published: January 2021

Mice bearing Robertsonian translocation chromosomes frequently produce aneuploid gametes. They are therefore excellent tools for studying nondisjunction in mammals. Genotypic analysis of embryos from a mouse cross between two different strains of mice carrying a (7,18) Robertsonian chromosome enabled us to measure the rate of nondisjunction for chromosomes 7 and 18. Embryos (429) were harvested from 76 litters of mice and the parental origin of each chromosome 7 and 18 determined. Genotyping these embryos has allowed us to conclude the following: (1) there were 96 embryos in which at least one nondisjunction event had taken place; (2) the rate of maternal nondisjunction was greater than paternal nondisjunction for teh chromosomes sampled in these mice; (3) a bias against chromosome 7 and 18 nullisomic gametes was observed, reflected in a smaller than expected number of uniparental disomic embryos; (4) nondisjunction events did not seem to occur at random throughout the 76 mouse litters, but were clustered into fewer than would be expected cy chance; and (5) a deficiency of paternal chromosome 18 uniparental disomic embryos was observed along with a higher than normal rate of developmental retardation at 8.5 days post coitum, raising the possibility that this chromosome has at least one imprinted gene.