bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Drosophila Suppressor of Underreplication Protein Binds to Late-Replicating Regions of Polytene Chromosomes
Authors: Makunin I V , Volkova E I , Belyaeva E S , Nabirochkina E N , Pirrotta V , Zhimulev I F 
Published: April 2021

Abstract
In many late-replicating euchromatic regions of salivary gland polytene chromosomes, DNA is underrep-resented. A mutation in the SuUR gene suppresses underreplication and leads to normal levels of DNA polytenization in these regions. We identified the SuUR gene and determined its structure. In the SuUR mutant stock a 6-kb insertion was found in the fourth exon of the gene. A single SuUR transcript is present at all stages of Drosophila development and is most abundant in adult females and embryos. The SuUR gene encodes a protein of 962 amino acids whose putative sequence is similar to the N-terminal part of SNF2/SWI2 proteins. Staining of salivary gland polytene chromosomes with antibodies directed against the SuUR protein shows that the protein is localized mainly in late-replicating regions and in regions of intercalary and pericentric heterochromatin.
Sequence of the Tribolium castaneum Homeotic Complex: The Region Corresponding to the Drosophila melanogaster Antennapedia Complex
Authors: Brown Susan J , Fellers John P , Shippy Teresa D , Richardson Elizabeth A , Maxwell Mark , Stuart Jeffery J , Denell Robin E 
Published: April 2021

Abstract
The homeotic selector genes of the red flour beetle, Tribolium castaneum, are located in a single cluster. We have sequenced the region containing the homeotic selector genes required for proper development of the head and anterior thorax, which is the counterpart of the ANTC in Drosophila. This 280-kb interval contains eight homeodomain-encoding genes, including single orthologs of the Drosophila genes labial, proboscipedia, Deformed, Sex combs reduced, fushi tarazu, and Antennapedia, as well as two orthologs of zerknüllt. These genes are all oriented in the same direction, as are the Hox genes of amphioxus, mice, and humans. Although each transcription unit is similar to its Drosophila counterpart in size, the Tribolium genes contain fewer introns (with the exception of the two zerknüllt genes), produce shorter mRNAs, and encode smaller proteins. Unlike the ANTC, this region of the Tribolium HOMC contains no additional genes.
Geographic Uniformity of the Lyme Disease Spirochete (Borrelia burgdorferi) and Its Shared History With Tick Vector (Ixodes scapularis) in the Northeastern United States
Authors: Qiu Wei-Gang , Dykhuizen Daniel E , Acosta Michael S , Luft Benjamin J 
Published: April 2021

Abstract
Over 80% of reported cases of Lyme disease in the United States occur in coastal regions of northeastern and mid-Atlantic states. The genetic structure of the Lyme disease spirochete (Borrelia burgdorferi) and its main tick vector (Ixodes scapularis) was studied concurrently and comparatively by sampling natural populations of I. scapularis ticks along the East Coast from 1996 to 1998. Borrelia is genetically highly diverse at the outer surface protein ospC. Since Borrelia is highly clonal, the ospC alleles can be used to define clones. A newly designed reverse line blotting (RLB) assay shows that up to 10 Borrelia clones can infect a single tick. The clone frequencies in Borrelia populations are the same across the Northeast. On the other hand, I. scapularis populations show strong regional divergence (among northeastern, mid-Atlantic, and southern states) as well as local differentiation. The high genetic diversity within Borrelia populations and the disparity in the genetic structure between Borrelia and its tick vector are likely consequences of strong balancing selection on local Borrelia clones. Demographically, both Borrelia and I. scapularis populations in the Northeast show the characteristics of a species that has recently expanded from a population bottleneck. Major geological and ecological events, such as the last glacial maximum (18,000 years ago) and the modern-day expansion of tick habitats, are likely causes of the observed “founder effects” for the two organisms in the Northeast. We therefore conclude that the genetic structure of B. burgdorferi has been intimately shaped by the natural history of its main vector, the northern lineage of I. scapularis ticks.
The Chromosome 1;11 Translocation Provides the Best Evidence Supporting Genetic Etiology for Schizophrenia and Bipolar Affective Disorders
Authors: Klar Amar J S 
Published: April 2021

Abstract
Genetics is assumed to cause susceptibility to psychosis, but no major locus has been identified. These disorders cosegregate with a chromosome 1;11 translocation in a Scottish pedigree where 50% of the carriers are diseased. A genetic model originally proposed to explain the basis of these illnesses predicts such an outcome.
Frequent Germline Mutations and Somatic Repeat Instability in DNA Mismatch-Repair-Deficient Caenorhabditis elegans
Authors: Tijsterman Marcel , Pothof Joris , Plasterk Ronald H A 
Published: April 2021

Abstract
Mismatch-repair-deficient mutants were initially recognized as mutation-prone derivatives of bacteria, and later mismatch repair deficiency was found to predispose humans to colon cancers (HNPCC). We generated mismatch-repair-deficient Caenorhabditis elegans by deleting the msh-6 gene and analyzed the fidelity of transmission of genetic information to subsequent generations. msh-6-defective animals show an elevated level of spontaneous mutants in both the male and female germline; also repeated DNA tracts are unstable. To monitor DNA repeat instability in somatic tissue, we developed a sensitive system, making use of heat-shock promoter-driven lacZ transgenes, but with a repeat that puts this reporter gene out of frame. In genetic msh-6-deficient animals lacZ+ patches are observed as a result of somatic repeat instability. RNA interference by feeding wild-type animals dsRNA homologous to msh-2 or msh-6 also resulted in somatic DNA instability, as well as in germline mutagenesis, indicating that one can use C. elegans as a model system to discover genes involved in maintaining DNA stability by large-scale RNAi screens.
Muller's Ratchet and the Pattern of Variation at a Neutral Locus
Authors: Gordo Isabel , Navarro Arcadio , Charlesworth Brian 
Published: April 2021

Abstract
The levels and patterns of variation at a neutral locus are analyzed in a haploid asexual population undergoing accumulation of deleterious mutations due to Muller's ratchet. We find that the movement of Muller's ratchet can be associated with a considerable reduction in genetic diversity below classical neutral expectation. The extent to which variability is reduced is a function of the deleterious mutation rate, the fitness effects of the mutations, and the population size. Approximate analytical expressions for the expected genetic diversity are compared with simulation results under two different models of deleterious mutations: a model where all deleterious mutations have equal effects and a model where there are two classes of deleterious mutations. We also find that Muller's ratchet can produce a considerable distortion in the neutral frequency spectrum toward an excess of rare variants.
kangaroo, a Mobile Element From Volvox carteri, Is a Member of a Newly Recognized Third Class of Retrotransposons
Authors: Duncan Leonard , Bouckaert Kristine , Yeh Fay , Kirk David L 
Published: April 2021

Abstract
Retrotransposons play an important role in the evolution of genomic structure and function. Here we report on the characterization of a novel retrotransposon called kangaroo from the multicellular green alga, Volvox carteri. kangaroo elements are highly mobile and their expression is developmentally regulated. They probably integrate via double-stranded, closed-circle DNA intermediates through the action of an encoded recombinase related to the λ-site-specific integrase. Phylogenetic analysis indicates that kangaroo elements are closely related to other unorthodox retrotransposons including PAT (from a nematode), DIRS-1 (from Dictyostelium), and DrDIRS1 (from zebrafish). PAT and kangaroo both contain split direct repeat (SDR) termini, and here we show that DIRS-1 and DrDIRS1 elements contain terminal features structurally related to SDRs. Thus, these mobile elements appear to define a third class of retrotransposons (the DIRS1 group) that are unified by common structural features, genes, and integration mechanisms, all of which differ from those of LTR and conventional non-LTR retrotransposons.
Likelihood and Bayes Estimation of Ancestral Population Sizes in Hominoids Using Data From Multiple Loci
Authors: Yang Ziheng 
Published: April 2021

Abstract
Polymorphisms in an ancestral population can cause conflicts between gene trees and the species tree. Such conflicts can be used to estimate ancestral population sizes when data from multiple loci are available. In this article I extend previous work for estimating ancestral population sizes to analyze sequence data from three species under a finite-site nucleotide substitution model. Both maximum-likelihood (ML) and Bayes methods are implemented for joint estimation of the two speciation dates and the two population size parameters. Both methods account for uncertainties in the gene tree due to few informative sites at each locus and make an efficient use of information in the data. The Bayes algorithm using Markov chain Monte Carlo (MCMC) enjoys a computational advantage over ML and also provides a framework for incorporating prior information about the parameters. The methods are applied to a data set of 53 nuclear noncoding contigs from human, chimpanzee, and gorilla published by Chen and Li. Estimates of the effective population size for the common ancestor of humans and chimpanzees by both ML and Bayes methods are ∼12,000-21,000, comparable to estimates for modern humans, and do not support the notion of a dramatic size reduction in early human populations. Estimates published previously from the same data are several times larger and appear to be biased due to methodological deficiency. The divergence between humans and chimpanzees is dated at ∼5.2 million years ago and the gorilla divergence 1.1-1.7 million years earlier. The analysis suggests that typical data sets contain useful information about the ancestral population sizes and that it is advantageous to analyze data of several species simultaneously.
Horizontal Acquisition of Divergent Chromosomal DNA in Bacteria: Effects of Mutator Phenotypes
Authors: Townsend Jeffrey P , Nielsen Kaare M , Fisher Daniel S , Hartl Daniel L 
Published: April 2021

Abstract
We examine the potential beneficial effects of the expanded access to environmental DNA offered by mutators on the adaptive potential of bacterial populations. Using parameters from published studies of recombination in E. coli, we find that the presence of mutators has the potential to greatly enhance bacterial population adaptation when compared to populations without mutators. In one specific example, for which three specific amino acid substitutions are required for adaptation to occur in a 300-amino-acid protein, we found a 3500-fold increase in the rate of adaptation. The probability of a beneficial acquisition decreased if more amino acid changes, or integration of longer DNA fragments, were required for adaptation. The model also predicts that mutators are more likely than nonmutator phenotypes to acquire genetic variability from a more diverged set of donor bacteria. Bacterial populations harboring mutators in a sequence heterogeneous environment are predicted to acquire most of their DNA conferring adaptation in the range of 13–30% divergence, whereas nonmutator phenotypes become adapted after recombining with more homogeneous sequences of 7–21% divergence. We conclude that mutators can accelerate bacterial adaptation when desired genetic variability is present within DNA fragments of up to ∼30% divergence.
Suppression of Muscle Hypercontraction by Mutations in the Myosin Heavy Chain Gene of Drosophila melanogaster
Authors: Nongthomba Upendra , Cummins Mark , Clark Samantha , Vigoreaux Jim O , Sparrow John C 
Published: April 2021

Abstract
The indirect flight muscles (IFM) of Drosophila melanogaster provide a good genetic system with which to investigate muscle function. Flight muscle contraction is regulated by both stretch and Ca2+-induced thin filament (actin + tropomyosin + troponin complex) activation. Some mutants in troponin-I (TnI) and troponin-T (TnT) genes cause a “hypercontraction” muscle phenotype, suggesting that this condition arises from defects in Ca2+ regulation and actomyosin-generated tension. We have tested the hypothesis that missense mutations of the myosin heavy chain gene, Mhc, which suppress the hypercontraction of the TnI mutant held-up2 (hdp2), do so by reducing actomyosin force production. Here we show that a “headless” Mhc transgenic fly construct that reduces the myosin head concentration in the muscle thick filaments acts as a dose-dependent suppressor of hypercontracting alleles of TnI, TnT, Mhc, and flightin genes. The data suggest that most, if not all, mutants causing hypercontraction require actomyosin-produced forces to do so. Whether all Mhc suppressors act simply by reducing the force production of the thick filament is discussed with respect to current models of myosin function and thin filament activation by the binding of calcium to the troponin complex.
Drosophila Gain-of-Function Mutant RTK Torso Triggers Ectopic Dpp and STAT Signaling
Authors: Li Jinghong , Li Willis X 
Published: April 2021

Abstract
Overactivation of receptor tyrosine kinases (RTKs) has been linked to tumorigenesis. To understand how a hyperactivated RTK functions differently from wild-type RTK, we conducted a genome-wide systematic survey for genes that are required for signaling by a gain-of-function mutant Drosophila RTK Torso (Tor). We screened chromosomal deficiencies for suppression of a gain-of-function mutation tor (torGOF), which led to the identification of 26 genomic regions that, when in half dosage, suppressed the defects caused by torGOF. Testing of candidate genes in these regions revealed many genes known to be involved in Tor signaling (such as those encoding the Ras-MAPK cassette, adaptor and structural molecules of RTK signaling, and downstream target genes of Tor), confirming the specificity of this genetic screen. Importantly, this screen also identified components of the TGFβ (Dpp) and JAK/STAT pathways as being required for TorGOF signaling. Specifically, we found that reducing the dosage of thickveins (tkv), Mothers against dpp (Mad), or STAT92E (aka marelle), respectively, suppressed torGOF phenotypes. Furthermore, we demonstrate that in torGOF embryos, dpp is ectopically expressed and thus may contribute to the patterning defects. These results demonstrate an essential requirement of noncanonical signaling pathways for a persistently activated RTK to cause pathological defects in an organism.
Is the Rate of Insertion and Deletion Mutation Male Biased?: Molecular Evolutionary Analysis of Avian and Primate Sex Chromosome Sequences
Authors: Sundström Hannah , Webster Matthew T , Ellegren Hans 
Published: April 2021

Abstract
The rate of mutation for nucleotide substitution is generally higher among males than among females, likely owing to the larger number of DNA replications in spermatogenesis than in oogenesis. For insertion and deletion (indel) mutations, data from a few human genetic disease loci indicate that the two sexes may mutate at similar rates, possibly because such mutations arise in connection with meiotic crossing over. To address origin- and sex-specific rates of indel mutation we have conducted the first large-scale molecular evolutionary analysis of indels in noncoding DNA sequences from sex chromosomes. The rates are similar on the X and Y chromosomes of primates but about twice as high on the avian Z chromosome as on the W chromosome. The fact that indels are not uncommon on the nonrecombining Y and W chromosomes excludes meiotic crossing over as the main cause of indel mutation. On the other hand, the similar rates on X and Y indicate that the number of DNA replications (higher for Y than for X) is also not the main factor. Our observations are therefore consistent with a role of both DNA replication and recombination in the generation of short insertion and deletion mutations. A significant excess of deletion compared to insertion events is observed on the avian W chromosome, consistent with gradual DNA loss on a nonrecombining chromosome.
Delineating the Requirements for Spontaneous DNA Damage Resistance Pathways in Genome Maintenance and Viability in Saccharomyces cerevisiae
Authors: Morey Natalie J , Doetsch Paul W , Jinks-Robertson Sue 
Published: April 2021

Abstract
Cellular metabolic processes constantly generate reactive species that damage DNA. To counteract this relentless assault, cells have developed multiple pathways to resist damage. The base excision repair (BER) and nucleotide excision repair (NER) pathways remove damage whereas the recombination (REC) and postreplication repair (PRR) pathways bypass the damage, allowing deferred removal. Genetic studies in yeast indicate that these pathways can process a common spontaneous lesion(s), with mutational inactivation of any pathway increasing the burden on the remaining pathways. In this study, we examine the consequences of simultaneously compromising three or more of these pathways. Although the presence of a functional BER pathway alone is able to support haploid growth, retention of the NER, REC, or PRR pathway alone is not, indicating that BER is the key damage resistance pathway in yeast and may be responsible for the removal of the majority of either spontaneous DNA damage or specifically those lesions that are potentially lethal. In the diploid state, functional BER, NER, or REC alone can support growth, while PRR alone is insufficient for growth. In diploids, the presence of PRR alone may confer a lethal mutation load or, alternatively, PRR alone may be insufficient to deal with potentially lethal, replication-blocking lesions.
Opposite Roles of the F-Box Protein Rcy1p and the GTPase-Activating Protein Gyp2p During Recycling of Internalized Proteins in Yeast
Authors: Lafourcade Céline , Galan Jean-Marc , Peter Matthias 
Published: April 2021

Abstract
The F-box protein Rcy1p is part of a non-SCF (Skp1p-cullin-F-box protein) complex involved in recycling of internalized material. Like rcy1Δ, cells lacking the Rab-GTPase Ypt6p or its heterodimeric GEFs Rgp1p and Ric1p are unable to recycle the v-SNARE Snc1p. Here we provide genetic evidence suggesting that Rcy1p is a positive regulator of Ypt6p. Deletion of the GAP Gyp2p restores recycling in rcy1Δ, while overexpression of an active form of Ypt6p partially suppresses the recycling defect of rcy1Δ cells. Conversely, overexpression of Gyp2p in wild-type cells interferes with recycling of GFP-Snc1p, and the cells accumulate membrane structures as evidenced by electron microscopy. Gyp2p-GFP is distributed throughout the cytoplasm and accumulates in punctate structures, which concentrate in an actin-dependent manner at sites of polarized growth. Taken together, our results suggest that the F-box protein Rcy1p may activate the Ypt6p GTPase module during recycling.
The Neural Receptor Protein Tyrosine Phosphatase DPTP69D Is Required During Periods of Axon Outgrowth in Drosophila
Authors: Desai Chand , Purdy Joy 
Published: April 2021

Abstract
We have isolated and characterized a series of 18 chemically induced alleles of Ptp69D ranging in strength from viable to worse than null, which represent unique tools for probing the structure, function, and signaling pathway of DPTP69D. Three alleles are strongly temperature sensitive and were used to define the developmental periods requiring DPTP69D function; adult health requires DPTP69D during the mid- to late-pupal stage, eclosion requires DPTP69D during the early to mid-larval stage, and larval survival requires DPTP69D during embryogenesis. Mutations predicted to abolish the phosphatase activity of the membrane proximal D1 domain severely reduce but do not abolish DPTP69D function. Six alleles appear null; only 20% of null homozygotes pupate and &lt;5% eclose, only to fall into the food and drown. One allele, Ptp69D7, confers axon and viability defects more severe than those of the null phenotype. Sequence analysis predicts that Ptp69D7 encodes a mutant protein that may bind but not release substrate. Like mutations in the protein tyrosine phosphatase gene Dlar, strong Ptp69D alleles cause the ISNb nerve to bypass its muscle targets. Genetic analysis reveals that the bypass defect in Dlar and Ptp69D mutants is dependent upon DPTP99A function, consistent with the hypothesis that DPTP69D and DLAR both counteract DPTP99A, allowing ISNb axons to enter their target muscle field.
Molecular Evolution and Recombination in Gender-Associated Mitochondrial DNAs of the Manila Clam Tapes philippinarum
Authors: Passamonti Marco , Boore Jeffrey L , Scali Valerio 
Published: April 2021

Abstract
Doubly uniparental inheritance (DUI) provides an intriguing system for addressing aspects of molecular evolution and intermolecular recombination of mitochondrial DNA. For this reason, a large sequence analysis has been performed on Tapes philippinarum (Bivalvia, Veneridae), which has mitochondrial DNA heteroplasmy that is consistent with a DUI. The sequences of a 9.2-kb region (containing 29 genes) from 9 individuals and the sequences of a single gene from another 44 individuals are analyzed. Comparisons suggest that the two sex-related mitochondrial genomes do not experience a neutral pattern of divergence and that selection may act with varying strength on different genes. This pattern of evolution may be related to the long, separate history of M and F genomes within their tissue-specific “arenas.” Moreover, our data suggest that recombinants, although occurring in soma, may seldom be transmitted to progeny in T. philippinarum.
Identification of Quantitative Trait Loci for Production Traits in Commercial Pig Populations
Authors: Evans G J , Giuffra E , Sanchez A , Kerje S , Davalos G , Vidal O , Illán S , Noguera J L , Varona L , Velander I , Southwood O I , de Koning D-J , Haley C S , Plastow G S , Andersson L 
Published: April 2021

Abstract
The aim of this study was to investigate methods for detecting QTL in outbred commercial pig populations. Several QTL for back fat and growth rate, previously detected in experimental resource populations, were examined for segregation in 10 different populations. Two hundred trait-by-population-by-chromosome tests were performed, resulting in 20 tests being significant at the 5% level. In addition, 53 QTL tests for 11 meat quality traits were declared significant, using a subset of the populations. These results show that a considerable amount of phenotypic variance observed in these populations can be explained by major alleles segregating at several of the loci described. Thus, despite a relatively strong selection pressure for growth and back fat traits in these populations, these alleles have not yet reached fixation. The approaches used here demonstrate that it is possible to verify segregation of QTL in commercial populations by limited genotyping of a selection of informative animals. Such verified QTL may be directly exploited in marker-assisted selection (MAS) programs in commercial populations and their molecular basis may be revealed by positional candidate cloning.