bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evolution of multilocus systems under weak selection.
Authors: Nagylaki T 
Published: January 2021

Abstract
The evolution of multilocus systems under weak selection is investigated. Generations are discrete and nonoverlapping; the monoecious population mates at random. The number of multi-allelic loci, the linkage map, dominance, and epistasis are arbitrary. The genotypic fitnesses may depend on the gametic frequencies and time. The results hold for s &lt; cmin, where s and cmin denote the selection intensity and the smallest two-locus recombination frequency, respectively. After an evolutionarily short time of t1 approximately (ln s)/ln(1 - cmin) generations, all the multilocus linkage disequilibria are of the order of s [i.e., O(s) as s--&gt;0], and then the population evolves approximately as if it were in linkage equilibrium, the error in the gametic frequencies being O(s). Suppose the explicit time dependence (if any) of the genotypic fitnesses is O(s2). Then after a time t2 approximately 2t1, the linkage disequilibria are nearly constant, their rate of change being O(s2). Furthermore, with an error of O(s2), each linkage disequilibrium is proportional to the corresponding epistatic deviation for the interaction of additive effects on fitness. If the genotypic fitnesses change no faster than at the rate O(s3), then the single-generation change in the mean fitness is delta W = W-1Vg+O(s3), where Vg designates the genic (or additive genetic) variance in fitness. The mean of a character with genotypic values whose single-generation change does not exceed O(s2) evolves at the rate delta Z = W-1Cg+O(s2), where Cg represents the genic covariance of the character and fitness (i.e., the covariance of the average effect on the character and the average excess for fitness of every allele that affects the character). Thus, after a short time t2, the absolute error in the fundamental and secondary theorems of natural selection is small, though the relative error may be large.
A cladistic analysis of phenotypic associations with haplotypes inferred from restriction endonuclease mapping. IV. Nested analyses with cladogram uncertainty and recombination.
Authors: Templeton A R , Sing C F 
Published: January 2021

Abstract
We previously developed an analytical strategy based on cladistic theory to identify subsets of haplotypes that are associated with significant phenotypic deviations. Our initial approach was limited to segments of DNA in which little recombination occurs. In such cases, a cladogram can be constructed from the restriction site data to estimate the evolutionary steps that interrelate the observed haplotypes to one another. The cladogram is then used to define a nested statistical design for identifying mutational steps associated with significant phenotypic deviations. The central assumption behind this strategy is that a mutation responsible for a particular phenotypic effect is embedded within the evolutionary history that is represented by the cladogram. The power of this approach depends on the accuracy of the cladogram in portraying the evolutionary history of the DNA region. This accuracy can be diminished both by recombination and by uncertainty in the estimated cladogram topology. In a previous paper, we presented an algorithm for estimating the set of likely claodgrams and recombination events. In this paper we present an algorithm for defining a nested statistical design under cladogram uncertainty and recombination. Given the nested design, phenotypic associations can be examined using either a nested analysis of variance (for haploids or homozygous strains) or permutation testing (for outcrossed, diploid gene regions). In this paper we also extend this analytical strategy to include categorical phenotypes in addition to quantitative phenotypes. Some worked examples are presented using Drosophila data sets. These examples illustrate that having some recombination may actually enhance the biological inferences that may derived from a cladistic analysis. In particular, recombination can be used to assign a physical localization to a given subregion for mutations responsible for significant phenotypic effects.
Positive and negative regulatory elements control expression of the yeast retrotransposon Ty3.
Authors: Bilanchone V W , Claypool J A , Kinsey P T , Sandmeyer S B 
Published: January 2021

Abstract
We report the results of an analysis of Ty3 transcription and identification of Ty3 regions that mediate pheromone and mating-type regulation to coordinate its expression with the yeast life cycle. A set of strains was constructed which was isogenic except for the number of Ty3 elements, which varied from zero to three. Analysis of Ty3 expression in these strains showed that each of the three elements was transcribed and that each element was regulated. Dissection of the long terminal repeat regulatory region by Northern blot analysis of deletion mutants and reporter gene analysis showed that the upstream junction of Ty3 with flanking chromosomal sequences contained a negative control region. A 19-bp fragment (positions 56-74) containing one consensus copy and one 7 of 8-bp match to the pheromone response element (PRE) consensus was sufficient to mediate pheromone induction in either haploid cell type. Deletion of this region, however, did not abolish expression, indicating that other sequences also activate transcription. A 24-bp block immediately downstream of the PRE region contained a sequence similar to the a1-alpha 2 consensus that conferred mating-type control. A single base pair mutation in the region separating the PRE and a1-alpha 2 sequences blocked pheromone induction, but not mating-type control. Thus, the long terminal repeat of Ty3 is a compact, highly regulated, mobile promoter which is responsive to cell type and mating.
Chromosome rearrangements recovered following transformation of Neurospora crassa.
Authors: Perkins D D , Kinsey J A , Asch D K , Frederick G D 
Published: January 2021

Abstract
New chromosome rearrangements were found in 10% or more of mitotically stable transformants. This was shown for transformations involving a variety of different markers, vectors and recipient strains. Breakpoints were randomly distributed among the seven linkage groups. Controls using untransformed protoplasts of the same strains contained almost no rearrangements. A study of molecularly characterized Am+ transformants showed that rearrangements are frequent when multiple ectopic integration events have occurred. In contrast, rearrangements are absent or infrequent when only the resident locus is restored to am+ by a homologous event. Sequences of the transforming vector were genetically linked to breakpoints in 6 of 10 translocations that were examined using Southern hybridization or colony blots.
The 3' regulatory region of the Abdominal-B gene: genetic analysis supports a model of reiterated and interchangeable regulatory elements.
Authors: Crosby M A , Lundquist E A , Tautvydas R M , Johnson J J 
Published: January 2021

Abstract
The Abdominal-B (Abd-B) gene is one of three genes in the bithorax complex, a cluster of homeotic genes in Drosophila. During embryogenesis Abd-B is expressed in a complex pattern, producing four different transcript classes, each of which exhibits a unique spatial pattern of expression. Proper regulation of the class A transcripts is required for appropriate development of the fifth through eighth abdominal segments and is mediated, in part, by a 60-kb regulatory region located 3' of the gene. We have isolated a new mutation, designated Abd-BCorset, which is caused by a deletion that leaves 15 kb of the 3' regulatory sequences immediately adjacent to the gene, but removes 45 kb of the more distant 3' regulatory elements. This mutation produces an unexpected homeotic segmental transformation of the fourth through seventh abdominal segments, and has been analyzed by genetic and molecular techniques. In situ hybridization to Abd-BCorset embryos shows a uniform and moderate level of the Abd-B class A transcript in the posterior abdomen, rather than the normal graded pattern of expression. Our analysis of the Abd-BCorset mutation has prompted a model of the 3' regulatory region of Abd-B based on reiterated cell type-specific elements controlled by adjacent position-sensitive activating elements. The gradient of Abd-B expression normally observed in the posterior abdomen appears to be achieved by varying the number of reiterated elements that are active in each segment.
The effect of selection on the phenotypic variance.
Authors: Shnol E E , Kondrashov A S 
Published: January 2021

Abstract
We consider the within-generation changes of phenotypic variance caused by selection w(x) which acts on a quantitative trait x. If before selection the trait has Gaussian distribution, its variance decreases if the second derivative of the logarithm of w(x) is negative for all x, while if it is positive for all x, the variance increases.
Antimutator mutations in the alpha subunit of Escherichia coli DNA polymerase III: identification of the responsible mutations and alignment with other DNA polymerases.
Authors: Fijalkowska I J , Schaaper R M 
Published: January 2021

Abstract
The dnaE gene of Escherichia coli encodes the DNA polymerase (alpha subunit) of the main replicative enzyme, DNA polymerase III holoenzyme. We have previously identified this gene as the site of a series of seven antimutator mutations that specifically decrease the level of DNA replication errors. Here we report the nucleotide sequence changes in each of the different antimutator dnaE alleles. For each a single, but different, amino acid substitution was found among the 1,160 amino acids of the protein. The observed substitutions are generally nonconservative. All affected residues are located in the central one-third of the protein. Some insight into the function of the regions of polymerase III containing the affected residues was obtained by amino acid alignment with other DNA polymerases. We followed the principles developed in 1990 by M. Delarue et al. who have identified in DNA polymerases from a large number of prokaryotic and eukaryotic sources three highly conserved sequence motifs, which are suggested to contain components of the polymerase active site. We succeeded in finding these three conserved motifs in polymerase III as well. However, none of the amino acid substitutions responsible for the antimutator phenotype occurred at these sites. This and other observations suggest that the effect of these mutations may be exerted indirectly through effects on polymerase conformation and/or DNA/polymerase interactions.
Physical mapping of meiotic crossover events in a 200-kb region of Neurospora crassa linkage group I.
Authors: Mautino M R , Haedo S D , Rosa A L 
Published: January 2021

Abstract
We propose a general restriction fragment length polymorphism-based strategy to analyze the distribution of meiotic crossover events throughout specific genetic intervals. We have isolated 64 recombinant chromosomes carrying independent meiotic crossover events in the genetic interval eth-1-un-2 on linkage group I of Neurospora crassa. Thirty-eight crossover events were physically mapped with reference to a 200-kb region cloned by chromosome walking, using N. crassa lambda and cosmid libraries. Crossovers were homogeneously distributed at intervals of 5.0 +/- 2.3 kb along the entire cloned interval. The ratio of physical to genetic distance appears to be higher in the region than in the overall N. crassa genome, suggesting that recombinational activity is less in large chromosomes than in small ones. The present work provides a method for defining the centromeric-telomeric orientation of single cloned DNA fragments. Their physical distance can also be estimated with respect to linked loci, provided that crossover events are distributed homogeneously in the interval. This strategy overcomes typical difficulties in defining the position and direction of chromosome walking steps on conventional linkage maps.
Mouse models of human phenylketonuria.
Authors: Shedlovsky A , McDonald J D , Symula D , Dove W F 
Published: January 2021

Abstract
Phenylketonuria (PKU) results from a deficiency in phenylalanine hydroxylase, the enzyme catalyzing the conversion of phenylalanine (PHE) to tyrosine. Although this inborn error of metabolism was among the first in humans to be understood biochemically and genetically, little is known of the mechanism(s) involved in the pathology of PKU. We have combined mouse germline mutagenesis with screens for hyperphenylalaninemia to isolate three mutants deficient in phenylalanine hydroxylase (PAH) activity and cross-reactive protein. Two of these have reduced PAH mRNA and display characteristics of untreated human PKU patients. A low PHE diet partially reverses these abnormalities. Our success in using high frequency random germline point mutagenesis to obtain appropriate disease models illustrates how such mutagenesis can complement the emergent power of targeted mutagenesis in the mouse. The mutants now can be used as models in studying both maternal PKU and somatic gene therapy.
The distribution and spreading of rare variants in the histone multigene family of Drosophila melanogaster.
Authors: Colby C , Williams S M 
Published: January 2021

Abstract
We surveyed the distribution of rare variant restriction sites within and among histone gene arrays of Drosophila melanogaster using restriction fragment length polymorphism (RFLP) analysis. Seventy-three naturally occurring arrays were digested with restriction enzymes that had no recognition sites in the published histone sequence. Of the arrays surveyed, 68.5% had at least two nonconsensus restriction sites present as indicated by the presence of a small band or bands on the autoradiographs. These bands were almost always the length of a single repeat in the histone multigene family or a multiple of this length. In arrays with more than one band, intensity of the bands almost always decreased with increasing size. This shows that within these arrays variant restriction sites were predominantly located on adjacent repeats. If these bands are caused by spreading of variant sites, as is most likely, then variants spread along the array as an inverse function of distance. Overall, if a sequence spread it had a 92% probability of ending up in its nearest neighbor. This pattern may result from the noncontiguous nature of the histone family.
A combined classical genetic and high resolution two-dimensional electrophoretic approach to the assessment of the number of genes affecting hybrid male sterility in Drosophila simulans and Drosophila sechellia.
Authors: Zeng L W , Singh R S 
Published: January 2021

Abstract
We have attempted to estimate the number of genes involved in postzygotic reproductive isolation between two closely related species, Drosophila simulans and Drosophila sechellia, by a novel approach that involves the use of high resolution two-dimensional gel electrophoresis (2DE) to examine testis proteins in parents, hybrids and fertile and sterile backcross progenies. The important results that have emerged from this study are as follows: (1) about 8% of about 1000 proteins examined showed divergence (presence/absence) between the two species; (2) by tracing individual proteins in parental, hybrid and backcross males, we were able to associate the divergent proteins with different chromosomes and found that most divergent proteins are associated with autosomes and very few with X chromosome, Y chromosome and cytoplasm; (3) when proteins showing both quantitative and qualitative differences between the two species were examined in F1 hybrid males, most (97.4%) proteins were expressed at levels between the two parents and no sign of large scale changes in spot density was observed. All the proteins observed in the two parental species were present in F1 hybrid males except two species-specific proteins that may be encoded (or regulated) by sex chromosomes; (4) when different fertile and sterile backcross male testes were compared, a few D. sechellia-specific proteins were identified to be consistently associated with male sterility. These results along with the observation that a large proportion (23.6%) of first generation backcross males were fertile show that hybrid male sterility between D. simulans and D. sechellia involves a relatively small number of genes. Role of large scale genetic changes due to general genome incompatibility is not supported. The results also suggest that the large effect of X chromosome on hybrid male sterility is not due to higher divergence of X chromosome than autosomes.
A mutation affecting the lactate dehydrogenase locus Ldh-1 in the mouse. II. Mechanism of the LDH-A deficiency associated with hemolytic anemia.
Authors: Pretsch W , Merkle S , Favor J , Werner T 
Published: January 2021

Abstract
A procarbazine hydrochloride-induced mutation at the Ldh-1 structural locus encoding the A subunit of lactate dehydrogenase (LDH) was used to study the molecular and metabolic basis of severe hemolytic anemia due to LDH-A deficiency in the mouse. The mutant allele designated Ldh-1a-m1Neu codes for an enzyme that as homotetramer differs from the wild-type enzyme by a marked instability, acidic shift of the pH profile, increased Km for pyruvate and altered inhibition by high concentrations of this substrate. Except for the latter, all these altered properties of the mutant protein contribute to the diminished LDH activity in heterozygous and homozygous mutant individuals. Impaired energy metabolism of erythrocytes indicated by a relatively low ATP concentration is suggested to result in cell death at the end of the reticulocyte stage leading to the expression of hemolytic anemia with extreme reticulocytosis and hyperbilirubinemia. Despite the severe anemia, affected homozygous mutants exhibit approximately normal body weight and do not show noticeable impairment of viability or fertility. To date no such condition is observed in man. This discrepancy is likely due to the fact that in human erythrocytes both LDH-A and LDH-B subunits are expressed such that homozygotes for a LDH-A or LDH-B deficiency would not result in a comparably extreme LDH activity deficiency.
Efficiency of generations for estimating marker-associated QTL effects by multiple regression.
Authors: Moreno-Gonzalez J 
Published: January 2021

Abstract
Knowledge about the efficiency of generations for estimating marker-associated QTLs is needed for selection. The objective of this paper is to develop a theory to compare the efficiency of segregating generations and testcrosses from the cross of two inbred lines differing in value for a quantitative trait (P1 x P2) for estimating additive, dominance and heterotic effects of QTLs by stepwise regression. An equation that predicts the smallest gene effect in genetic standard deviation units that can be detected with 50% chance at a significance level as a function of the heritability (h2) and the recombination frequency (r) of markers was developed for the segregating generations and testcrosses. For estimating additive effects, the most efficient generation was the doubled-haploid (DH) lines; the most inefficient was the North Carolina Design III (NCD III), followed by selfed backcrosses (SB); the selfed families from F2 individual plants (F2:3 lines) are inferior to the recombinant inbreds (RI) for low r, but are better than RI for high h2 and r. Dominance effects are less efficiently estimated than additive effects. The NCD III is better than the SB and the F2:3 lines for detecting dominance effects. The RI and DH do not estimate dominance effects. The differential heterotic QTL effects of lines P1 and P2 when crossed with tester T can be estimated by evaluating testcrosses of individual F2 plants (F2T), recombinant inbreds (RIT) and double-haploid lines (DHT). The DHT is superior to the other generations. The F2T is better than the RIT for r &gt; or = 0.20, but inferior for r &lt; or = 0.1 or low heritability.
The Drosophila melanogaster suppressor of Hairy-wing zinc finger protein has minimal effects on gene expression in Saccharomyces cerevisiae.
Authors: Kim J , Shen B , Dorsett D 
Published: January 2021

Abstract
Many mutations in Drosophila melanogaster are gypsy retrotransposon insertions. Gypsy binds the protein (SUHW) encoded by the suppressor of Hairy-wing [su(Hw)] gene, and SUHW alters expression of surrounding genes. When gypsy is between an enhancer and promoter, SUHW blocks activation of transcription by the enhancer. Additionally, when gypsy is downstream of a promoter in a parallel orientation, SUHW increases truncation of transcripts at the poly(A) site in the gypsy 5' long terminal repeat, thereby decreasing the gene transcript levels. The effects of SUHW appear to involve fundamental and general mechanisms controlling gene expression because SUHW potentiates other poly(A) sites and blocks several enhancers in Drosophila. To investigate these mechanisms, SUHW was expressed in Saccharomyces cerevisiae. Although SUHW enters the nucleus and binds DNA in yeast, it has surprisingly minor effects on utilization of the CYC1 poly(A) site and transcription activation by a GAL upstream activation sequence. These observations indicate that the observed effects of SUHW on gene expression in Drosophila require specific interactions with other factors that are absent or unrecognizable in yeast.
An efficient positive selection procedure for the isolation of peroxisomal import and peroxisome assembly mutants of Saccharomyces cerevisiae.
Authors: Elgersma Y , van den Berg M , Tabak H F , Distel B 
Published: January 2021

Abstract
To study peroxisome biogenesis, we developed a procedure to select for Saccharomyces cerevisiae mutants defective in peroxisomal protein import or peroxisome assembly. For this purpose, a chimeric gene was constructed encoding the bleomycin resistance protein linked to the peroxisomal protein luciferase. In wild-type cells this chimeric protein is imported into the peroxisome, which prevents the neutralizing interaction of the chimeric protein with its toxic phleomycin ligand. Peroxisomal import and peroxisome assembly mutants are unable to import this chimeric protein into their peroxisomes. This enables the bleomycin moiety of the chimeric protein to bind phleomycin, thereby preventing its toxicity. The selection is very efficient: upon mutagenesis, 84 (10%) of 800 phleomycin resistant colonies tested were unable to grow on oleic acid. This rate could be increased to 25% using more stringent selection conditions. The selection procedure is very specific; all oleic acid non utilizing (onu) mutants tested were disturbed in peroxisomal import and/or peroxisome assembly. The pas (peroxisome assembly) mutants that have been used for complementation analysis represent 12 complementation groups including three novel ones, designated pas20, pas21 and pas22.