bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mytilus Mitochondrial DNA Contains a Functional Gene for a tRNASer(UCN) With a Dihydrouridine Arm-Replacement Loop and a pseudo-tRNASer(UCN) Gene
Authors: Beagley C Timothy , Okimoto Ronald , Wolstenholme David R 
Published: April 2021

Abstract
A 2500-nucleotide pair (ntp) sequence of F-type mitochondrial (mt) DNA of the Pacific Rim mussel Mytilus californianus (class Bivalvia, phylum Mollusca) that contains two complete (ND2 and ND3) and two partial (COI and COIII) protein genes and nine tRNA genes is presented. Seven of the encoded tRNAs (Ala, Arg, His, Met(AUA), Pro, Ser(UCN), and Trp) have the potential to fold into the orthodox four-armed tRNA secondary structure, while two [tRNASer(AGN) and a second tRNASer(UCN)] will fold only into tRNAs with a dihydrouridine (DHU) arm-replacement loop. Comparison of these mt-tRNA gene sequences with previously published, corresponding M. edulis F-type mtDNA indicates that similarity between the four-armed tRNASer(UCN) genes is only 63.8% compared with an average of 92.1% (range 86.2-98.5%) for the remaining eight tRNA genes. Northern blot analysis indicated that mature tRNAs encoded by the DHU arm-replacement loop-containing tRNASer(UCN), tRNASer(AGN), tRNAMet(AUA), tRNATrp, and tRNAPro genes occur in M. californianus mitochondria, strengthening the view that all of these genes are functional. However, Northern blot and 5′ RACE (rapid amplification of cDNA ends) analyses indicated that the four-armed tRNASer(UCN) gene is transcribed into a stable RNA that includes the downstream COI sequence and is not processed into a mature tRNA. On the basis of these observations the M. californianus and M. edulis four-armed tRNASer(UCN) sequences are interpreted as pseudo-tRNASer(UCN) genes.
Among-Locus Variation in Fst: Fish, Allozymes and the Lewontin-Krakauer Test Revisited
Authors: Baer Charles F 
Published: April 2021

Abstract
Variation among loci in the distribution of allele frequencies among subpopulations is well known; how to tell when the variation exceeds that expected when all loci are subject to uniform evolutionary processes is not well known. If locus-specific effects are important, the ability to detect those effects should vary with the level of gene flow. Populations with low gene flow should exhibit greater variation among loci in Fst than populations with high gene flow, because gene flow acts to homogenize allele frequencies among subpopulations. Here I use Lewontin and Krakauer’s k statistic to describe the variance among allozyme loci in 102 published data sets from fishes. As originally proposed, k ⪢ 2 was considered evidence that the variation in Fst among loci is greater than expected from neutral evolution. Although that interpretation is invalid, large differences in k in different populations suggest that locus-specific forces may be important in shaping genetic diversity. In these data, k is not greater for populations with expected low levels of gene flow than for populations with expected high levels of gene flow. There is thus no evidence that locus-specific forces are of general importance in shaping the distribution of allele frequencies at enzyme loci among populations of fishes.
The Causes of Synonymous Rate Variation in the Rodent Genome: Can Substitution Rates Be Used to Estimate the Sex Bias in Mutation Rate?
Authors: Smith Nick G C , Hurst Laurence D 
Published: April 2021

AbstractMiyata et al. have suggested that the male-to-female mutation rate ratio (α) can be estimated by comparing the neutral substitution rates of X-linked (X), Y-linked (Y), and autosomal (A) genes. Rodent silent site X/A comparisons provide very different estimates from X/Y comparisons. We examine three explanations for this discrepancy: (1) statistical biases and artifacts, (2) nonneutral evolution, and (3) differences in mutation rate per germline replication. By estimating errors and using a variety of methodologies, we tentatively reject explanation 1. Our analyses of patterns of codon usage, synonymous rates, and nonsynonymous rates suggest that silent sites in rodents are evolving neutrally, and we can therefore reject explanation 2. We find both base composition and methylation differences between the different sets of chromosomes, a result consistent with explanation 3, but these differences do not appear to explain the observed discrepancies in estimates of α. Our finding of significantly low synonymous substitution rates in genomically imprinted genes suggests a link between hemizygous expression and an adaptive reduction in the mutation rate, which is consistent with explanation 3. Therefore our results provide circumstantial evidence in favor of the hypothesis that the discrepancies in estimates of α are due to differences in the mutation rate per germline replication between different parts of the genome. This explanation violates a critical assumption of the method of Miyata et al., and hence we suggest that estimates of α, obtained using this method, need to be treated with caution.
Intrachromosomal Recombination Between Well-Separated, Homologous Sequences in Mammalian Cells
Authors: Baker Mark D , Read Leah R , Ng Philip , Beatty Barbara G 
Published: April 2021

Abstract
In the present study, we investigated intrachromosomal homologous recombination in a murine hybridoma in which the recipient for recombination, the haploid, endogenous chromosomal immunoglobulin μ-gene bearing a mutation in the constant (Cμ) region, was separated from the integrated single copy wild-type donor Cμ region by ∼1 Mb along the hybridoma chromosome. Homologous recombination between the donor and recipient Cμ region occurred with high frequency, correcting the mutant chromosomal μ-gene in the hybridoma. This enabled recombinant hybridomas to synthesize normal IgM and to be detected as plaque-forming cells (PFC). Characterization of the recombinants revealed that they could be placed into three distinct classes. The generation of the class I recombinants was consistent with a simple unequal sister chromatid exchange (USCE) between the donor and recipient Cμ region, as they contained the three Cμ-bearing fragments expected from this recombination, the original donor Cμ region along with both products of the single reciprocal crossover. However, a simple mechanism of homologous recombination was not sufficient in explaining the more complex Cμ region structures characterizing the class II and class III recombinants. To explain these recombinants, a model is proposed in which unequal pairing between the donor and recipient Cμ regions located on sister chromatids resulted in two crossover events. One crossover resulted in the deletion of sequences from one chromatid forming a DNA circle, which then integrated into the sister chromatid by a second reciprocal crossover.
Origin of Gene Overlap: The Case of TCP1 and ACAT2
Authors: Shintani Seikou , O’hUigin Colm , Toyosawa Satoru , Michalová Věra , Klein Jan 
Published: April 2021

Abstract
The human acetyl-CoA acetyltransferase 2 gene, ACAT2, codes for a thiolase, an enzyme involved in lipid metabolism. The human T-complex protein 1 gene, TCP1, encodes a molecular chaperone of the chaperonin family. The two genes overlap by their 3′-untranslated regions, their coding sequences being located on opposite DNA strands in a tail-to-tail orientation. To find out how the overlap might have arisen in evolution, the homologous genes of the zebrafish, the African toad, caiman, platypus, opossum, and wallaby were identified. In each species, standard or long polymerase chain reactions were used to determine whether the ACAT2 and TCP1 homologs are closely linked and, if so, whether they overlap. The results reveal that the overlap apparently arose during the transition from therapsid reptiles to mammals and has been retained for &gt;200 million years. Part of the overlapping untranslated region shows remarkable sequence conservation. The overlap presumably arose during the chromosomal rearrangement that brought the two unrelated and previously separated genes together. One or both of the transposed genes found by chance signals that are necessary for the processing of their transcripts to be present on the noncoding strand of the partner gene.
Molecular Cloning and Tissue-Specific Expression of the mutator2 Gene (mu2) in Drosophila melanogaster
Authors: Kasravi Armin , Walter Marika F , Brand Stephanie , Mason James M , Biessmann Harald 
Published: April 2021

Abstract
We present here the molecular cloning and characterization of the mutator2 (mu2) gene of Drosophila melanogaster together with further genetic analyses of its mutant phenotype. mu2 functions in oogenesis during meiotic recombination, during repair of radiation damage in mature oocytes, and in proliferating somatic cells, where mu2 mutations cause an increase in somatic recombination. Our data show that mu2 represents a novel component in the processing of double strand breaks (DSBs) in female meiosis. mu2 does not code for a DNA repair enzyme because mu2 mutants are not hypersensitive to DSB-inducing agents. We have mapped and cloned the mu2 gene and rescued the mu2 phenotype by germ-line transformation with genomic DNA fragments containing the mu2 gene. Sequencing its cDNA demonstrates that mu2 encodes a novel 139-kD protein, which is highly basic in the carboxy half and carries three nuclear localization signals and a helix-loop-helix domain. Consistent with the sex-specific mutant phenotype, the gene is expressed in ovaries but not in testes. During oogenesis its RNA is rapidly transported from the nurse cells into the oocyte where it accumulates specifically at the anterior margin. Expression is also prominent in diploid proliferating cells of larval somatic tissues. Our genetic and molecular data are consistent with the model that mu2 encodes a structural component of the oocyte nucleus. The MU2 protein may be involved in controlling chromatin structure and thus may influence the processing of DNA DSBs.
Clustered Microsatellite Mutations in the Pipefish Syngnathus typhle
Authors: Jones Adam G , Rosenqvist Gunilla , Berglund Anders , Avise John C 
Published: April 2021

AbstractClustered mutations are copies of a mutant allele that enter a population's gene pool together due to replication from a premeiotic germline mutation and distribution to multiple successful gametes of an individual. Although the phenomenon has been studied in Drosophila and noted in a few other species, the topic has received scant attention despite claims of being of major importance to population genetics theory. Here we capitalize upon the reproductive biology of male-pregnant pipefishes to document the occurrence of clustered microsatellite mutations and to estimate their rates and patterns from family data. Among a total of 3195 embryos genetically screened from 110 families, 40% of the 35 detected de novo mutant alleles resided in documented mutational clusters. Most of the microsatellite mutations appeared to involve small-integer changes in repeat copy number, and they arose in approximately equal frequency in paternal and maternal germlines. These findings extend observations on clustered mutations to another organismal group and motivate a broader critique of the mutation cluster phenomenon. They also carry implications for the evolution of microsatellites with respect to mutational models and homoplasy among alleles.
Estimation of Past Demographic Parameters From the Distribution of Pairwise Differences When the Mutation Rates Vary Among Sites: Application to Human Mitochondrial DNA
Authors: Schneider Stefan , Excoffier Laurent 
Published: April 2021

Abstract
Distributions of pairwise differences often called “mismatch distributions” have been extensively used to estimate the demographic parameters of past population expansions. However, these estimations relied on the assumption that all mutations occurring in the ancestry of a pair of genes lead to observable differences (the infinite-sites model). This mutation model may not be very realistic, especially in the case of the control region of mitochondrial DNA, where this methodology has been mostly applied. In this article, we show how to infer past demographic parameters by explicitly taking into account a finite-sites model with heterogeneity of mutation rates. We also propose an alternative way to derive confidence intervals around the estimated parameters, based on a bootstrap approach. By checking the validity of these confidence intervals by simulations, we find that only those associated with the timing of the expansion are approximately correctly estimated, while those around the population sizes are overly large. We also propose a test of the validity of the estimated demographic expansion scenario, whose proper behavior is verified by simulation. We illustrate our method with human mitochondrial DNA, where estimates of expansion times are found to be 10–20% larger when taking into account heterogeneity of mutation rates than under the infinite-sites model.
Spatial and Temporal Distribution of the Neutral Polymorphisms in the Last ZFX Intron: Analysis of the Haplotype Structure and Genealogy
Authors: Jaruzelska Jadwiga , Zietkiewicz Ewa , Batzer Mark , Cole David E C , Moisan Jean-Paul , Scozzari Rosaria , Tavar&eacute Simon , Labuda Damian 
Published: April 2021

Abstract
With 10 segregating sites (simple nucleotide polymorphisms) in the last intron (1089 bp) of the ZFX gene we have observed 11 haplotypes in 336 chromosomes representing a worldwide array of 15 human populations. Two haplotypes representing 77% of all chromosomes were distributed almost evenly among four continents. Five of the remaining haplotypes were detected in Africa and 4 others were restricted to Eurasia and the Americas. Using the information about the ancestral state of the segregating positions (inferred from human-great ape comparisons), we applied coalescent analysis to estimate the age of the polymorphisms and the resulting haplotypes. The oldest haplotype, with the ancestral alleles at all the sites, was observed at low frequency only in two groups of African origin. Its estimated age of 740 to 1100 kyr corresponded to the time to the most recent common ancestor. The two most frequent worldwide distributed haplotypes were estimated at 550 to 840 and 260 to 400 kyr, respectively, while the age of the continentally restricted polymorphisms was 120 to 180 kyr and smaller. Comparison of spatial and temporal distribution of the ZFX haplotypes suggests that modern humans diverged from the common ancestral stock in the Middle Paleolithic era. Subsequent range expansion prevented substantial gene flow among continents, separating African groups from populations that colonized Eurasia and the New World.
A Molecular Description of Mutations Affecting the Pollen Component of the Nicotiana alata S locus
Authors: Golz J F , Su V , Clarke A E , Newbigin E 
Published: April 2021

Abstract
Mutations affecting the self-incompatibility response of Nicotiana alata were generated by irradiation. Mutants in the M1 generation were selected on the basis of pollen tube growth through an otherwise incompatible pistil. Twelve of the 18 M1 plants obtained from the mutagenesis screen were self-compatible. Eleven self-compatible plants had mutations affecting only the pollen function of the S locus (pollen-part mutants). The remaining self-compatible plant had a mutation affecting only the style function of the S locus (style-part mutant). Cytological examination of the pollen-part mutant plants revealed that 8 had an extra chromosome (2n + 1) and 3 did not. The pollen-part mutation in 7 M1 plants was followed in a series of crosses. DNA blot analysis using probes for S-RNase genes (encoding the style function of the S locus) indicated that the pollen-part mutation was associated with an extra S allele in 4 M1 plants. In 3 of these plants, the extra S allele was located on the additional chromosome. There was no evidence of an extra S allele in the 3 remaining M1 plants. The breakdown of self-incompatibility in plants with an extra S allele is discussed with reference to current models of the molecular basis of self-incompatibility.
Probability of Identity by Descent in Metapopulations
Authors: Kaj Ingemar , Lascoux Martin 
Published: April 2021

Abstract
Equilibrium probabilities of identity by descent (IBD), for pairs of genes within individuals, for genes between individuals within subpopulations, and for genes between subpopulations are calculated in metapopulation models with fixed or varying colony sizes. A continuous-time analog to the Moran model was used in either case. For fixed-colony size both propagule and migrant pool models were considered. The varying population size model is based on a birth-death-immigration (BDI) process, to which migration between colonies is added. Wright's F statistics are calculated and compared to previous results. Adding between-island migration to the BDI model can have an important effect on the equilibrium probabilities of IBD and on Wright's index.
In Vivo Analysis of the Domains of Yeast Rvs167p Suggests Rvs167p Function Is Mediated Through Multiple Protein Interactions
Authors: Colwill Karen , Field Deborah , Moore Lynda , Friesen James , Andrews Brenda 
Published: April 2021

Abstract
Morphological changes during cell division in the yeast Saccharomyces cerevisiae are controlled by cell-cycle regulators. The Pcl-Pho85p kinase complex has been implicated in the regulation of the actin cytoskeleton at least in part through Rvs167p. Rvs167p consists of three domains called BAR, GPA, and SH3. Using a two-hybrid assay, we demonstrated that each region of Rvs167p participates in protein-protein interactions: the BAR domain bound the BAR domain of another Rvs167p protein and that of Rvs161p, the GPA region bound Pcl2p, and the SH3 domain bound Abp1p. We identified Rvs167p as a Las17p/Bee1p-interacting protein in a two-hybrid screen and showed that Las17p/Bee1p bound the SH3 domain of Rvs167p. We tested the extent to which the Rvs167p protein domains rescued phenotypes associated with deletion of RVS167: salt sensitivity, random budding, and endocytosis and sporulation defects. The BAR domain was sufficient for full or partial rescue of all rvs167 mutant phenotypes tested but not required for the sporulation defect for which the SH3 domain was also sufficient. Overexpression of Rvs167p inhibits cell growth. The BAR domain was essential for this inhibition and the SH3 domain had only a minor effect. Rvs167p may link the cell cycle regulator Pcl-Pho85p kinase and the actin cytoskeleton. We propose that Rvs167p is activated by phosphorylation in its GPA region by the Pcl-Pho85p kinase. Upon activation, Rvs167p enters a multiprotein complex, making critical contacts in its BAR domain and redundant or minor contacts with its SH3 domain.
A General Requirement for the Sin3-Rpd3 Histone Deacetylase Complex in Regulating Silencing in Saccharomyces cerevisiae
Authors: Sun Zu-Wen , Hampsey Michael 
Published: April 2021

Abstract
The Sin3-Rpd3 histone deacetylase complex, conserved between human and yeast, represses transcription when targeted by promoter-specific transcription factors. SIN3 and RPD3 also affect transcriptional silencing at the HM mating loci and at telomeres in yeast. Interestingly, however, deletion of the SIN3 and RPD3 genes enhances silencing, implying that the Sin3-Rpd3 complex functions to counteract, rather than to establish or maintain, silencing. Here we demonstrate that Sin3, Rpd3, and Sap30, a novel component of the Sin3-Rpd3 complex, affect silencing not only at the HMR and telomeric loci, but also at the rDNA locus. The effects on silencing at all three loci are dependent upon the histone deacetylase activity of Rpd3. Enhanced silencing associated with sin3Δ, rpd3Δ, and sap30Δ is differentially dependent upon Sir2 and Sir4 at the telomeric and rDNA loci and is also dependent upon the ubiquitin-conjugating enzyme Rad6 (Ubc2). We also show that the Cac3 subunit of the CAF-I chromatin assembly factor and Sin3-Rpd3 exert antagonistic effects on silencing. Strikingly, deletion of GCN5, which encodes a histone acetyltransferase, enhances silencing in a manner similar to deletion of RPD3. A model that integrates the effects of rpd3Δ, gcn5Δ, and cac3Δ on silencing is proposed.
DNA Sequence and Functional Analysis of Homologous ARS Elements of Saccharomyces cerevisiae and S. carlsbergensis
Authors: Theis James F , Yang Chen , Schaefer Christopher B , Newlon Carol S 
Published: April 2021

Abstract
ARS elements of Saccharomyces cerevisiae are the cis-acting sequences required for the initiation of chromosomal DNA replication. Comparisons of the DNA sequences of unrelated ARS elements from different regions of the genome have revealed no significant DNA sequence conservation. We have compared the sequences of seven pairs of homologous ARS elements from two Saccharomyces species, S. cerevisiae and S. carlsbergensis. In all but one case, the ARS308-ARS308carl pair, significant blocks of homology were detected. In the cases of ARS305, ARS307, and ARS309, previously identified functional elements were found to be conserved in their S. carlsbergensis homologs. Mutation of the conserved sequences in the S. carlsbergensis ARS elements revealed that the homologous sequences are required for function. These observations suggested that the sequences important for ARS function would be conserved in other ARS elements. Sequence comparisons aided in the identification of the essential matches to the ARS consensus sequence (ACS) of ARS304, ARS306, and ARS310carl, though not of ARS310.
Dictyostelium Myosin II G680V Suppressors Exhibit Overlapping Spectra of Biochemical Phenotypes Including Facilitated Phosphate Release
Authors: Wu Yuan , Nejad Mike , Patterson Bruce 
Published: April 2021

Abstract
We have biochemically characterized 13 intragenic suppressors of the G680V mutation of Dictyostelium myosin II. In the absence of the G680V mutation, the suppressors result in a number of deviant behaviors, most commonly an increase in the basal (actin-independent) ATPase of the motor. This phenotype is complementary to that of the G680V mutant and supports our proposal that the latter impairs phosphate release. Different subsets of the mutants also suffer from poor ATPase enhancement by 1 mg/ml actin, failure to release from actin in the presence of ATPγS (or ADP and salt), and excessive release from actin in the presence of ADP. The patterns of suppressor behaviors suggest that, in general, they are facilitating Pi-releasing state(s) of the motor, but that different individual suppressors may secondarily perturb other states or actions of the motor.