bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mixed-Model Reanalysis of Primate Data Suggests Tissue and Species Biases in Oligonucleotide-Based Gene Expression Profiles
Authors: Hsieh Wen-Ping , Chu Tzu-Ming , Wolfinger Russell D , Gibson Greg 
Published: April 2021

Abstract
An emerging issue in evolutionary genetics is whether it is possible to use gene expression profiling to identify genes that are associated with morphological, physiological, or behavioral divergence between species and whether these genes have undergone positive selection. Some of these questions were addressed in a recent study (Enard et al. 2002) of the difference in gene expression among human, chimp, and orangutan, which suggested an accelerated rate of divergence in gene expression in the human brain relative to liver. Reanalysis of the Affymetrix data set using analysis of variance methods to quantify the contributions of individuals and species to variation in expression of 12,600 genes indicates that as much as one-quarter of the genome shows divergent expression between primate species at the 5% level. The magnitude of fold change ranges from 1.2-fold up to 8-fold. Similar conclusions apply to reanalysis of Enard et al.'s (2002) parallel murine data set. However, biases inherent to short oligonucleotide microarray technology may account for some of the tissue and species effects. At high significance levels, more differences were observed in the liver than in the brain in each of the pairwise species comparisons, so it is not clear that expression divergence is accelerated in the human brain. Further, there is an apparent bias toward upregulation of gene expression in the brain in both primates and mice, whereas genes are equally likely to be up- or downregulated in the liver when these species diverge. A small subset of genes that are candidates for adaptive divergence may be identified on the basis of a high ratio of interspecific to intraspecific divergence.
A Conservative Test of Genetic Drift in the Endosymbiotic Bacterium Buchnera: Slightly Deleterious Mutations in the Chaperonin groEL
Authors: Herbeck Joshua T , Funk Daniel J , Degnan Patrick H , Wernegreen Jennifer J 
Published: April 2021

Abstract
The obligate endosymbiotic bacterium Buchnera aphidicola shows elevated rates of sequence evolution compared to free-living relatives, particularly at nonsynonymous sites. Because Buchnera experiences population bottlenecks during transmission to the offspring of its aphid host, it is hypothesized that genetic drift and the accumulation of slightly deleterious mutations can explain this rate increase. Recent studies of intraspecific variation in Buchnera reveal patterns consistent with this hypothesis. In this study, we examine inter- and intraspecific nucleotide variation in groEL, a highly conserved chaperonin gene that is constitutively overexpressed in Buchnera. Maximum-likelihood estimates of nonsynonymous substitution rates across Buchnera species are strikingly low at groEL compared to other loci. Despite this evidence for strong purifying selection on groEL, our intraspecific analysis of this gene documents reduced synonymous polymorphism, elevated nonsynonymous polymorphism, and an excess of rare alleles relative to the neutral expectation, as found in recent studies of other Buchnera loci. Comparisons with Escherichia coli generally show patterns predicted by their differences in Ne. The sum of these observations is not expected under relaxed or balancing selection, selective sweeps, or increased mutation rate. Rather, they further support the hypothesis that drift is an important force driving accelerated protein evolution in this obligate mutualist.
Polymorphism, Recombination and Alternative Unscrambling in the DNA Polymerase α Gene of the Ciliate Stylonychia lemnae (Alveolata; class Spirotrichea)
Authors: Ardell David H , Lozupone Catherine A , Landweber Laura F 
Published: April 2021

Abstract
DNA polymerase α is the most highly scrambled gene known in stichotrichous ciliates. In its hereditary micronuclear form, it is broken into &gt;40 pieces on two loci at least 3 kb apart. Scrambled genes must be reassembled through developmental DNA rearrangements to yield functioning macronuclear genes, but the mechanism and accuracy of this process are unknown. We describe the first analysis of DNA polymorphism in the macronuclear version of any scrambled gene. Six functional haplotypes obtained from five Eurasian strains of Stylonychia lemnae were highly polymorphic compared to Drosophila genes. Another incompletely unscrambled haplotype was interrupted by frameshift and nonsense mutations but contained more silent mutations than expected by allelic inactivation. In our sample, nucleotide diversity and recombination signals were unexpectedly high within a region encompassing the boundary of the two micronuclear loci. From this and other evidence we infer that both members of a long repeat at the ends of the loci provide alternative substrates for unscrambling in this region. Incongruent genealogies and recombination patterns were also consistent with separation of the two loci by a large genetic distance. Our results suggest that ciliate developmental DNA rearrangements may be more probabilistic and error prone than previously appreciated and constitute a potential source of macronuclear variation. From this perspective we introduce the nonsense-suppression hypothesis for the evolution of ciliate altered genetic codes. We also introduce methods and software to calculate the likelihood of hemizygosity in ciliate haplotype samples and to correct for multiple comparisons in sliding-window analyses of Tajima's D.
Caenorhabditis elegans Gαq Regulates Egg-Laying Behavior via a PLCβ-Independent and Serotonin-Dependent Signaling Pathway and Likely Functions Both in the Nervous System and in Muscle
Authors: Bastiani Carol A , Gharib Shahla , Simon Melvin I , Sternberg Paul W 
Published: April 2021

Abstract
egl-30 encodes the single C. elegans ortholog of vertebrate Gαq family members. We analyzed the expression pattern of EGL-30 and found that it is broadly expressed, with highest expression in the nervous system and in pharyngeal muscle. We isolated dominant, gain-of-function alleles of egl-30 as intragenic revertants of an egl-30 reduction-of-function mutation. Using these gain-of-function mutants and existing reduction-of-function mutants, we examined the site and mode of action of EGL-30. On the basis of pharmacological analysis, it has been determined that egl-30 functions both in the nervous system and in the vulval muscles for egg-laying behavior. Genetic epistasis over mutations that eliminate detectable levels of serotonin reveals that egl-30 requires serotonin to regulate egg laying. Furthermore, pharmacological response assays strongly suggest that EGL-30 may directly couple to a serotonin receptor to mediate egg laying. We also examined genetic interactions with mutations in the gene that encodes the single C. elegans homolog of PLCβ and mutations in genes that encode signaling molecules downstream of PLCβ. We conclude that PLCβ functions in parallel with egl-30 with respect to egg laying or is not the major effector of EGL-30. In contrast, PLCβ-mediated signaling is likely downstream of EGL-30 with respect to pharyngeal-pumping behavior. Our data indicate that there are multiple signaling pathways downstream of EGL-30 and that different pathways could predominate with respect to the regulation of different behaviors.
Characterization of a Male-Predominant Antisense Transcript Underexpressed in Hybrids ofDrosophila pseudoobscuraandD. persimilis
Authors: Noor Mohamed A F , Michalak Pawel , Donze David 
Published: April 2021

AbstractCharacterizing genes that are misregulated in hybrids may elucidate the genetic basis of hybrid sterility or other hybrid dysfunctions that contribute to speciation. Previously, a small segment of a male-predominant transcript that is underexpressed in adult male hybrids of Drosophila pseudoobscura and D. persimilis relative to pure species was identified in a differential display screen. Here, we obtained the full sequence of this 1330-bp transcript and determined that it is an antisense message with high sequence similarity to the D. melanogaster TRAP100 gene, part of the Mediator protein complex that regulates transcriptional initiation during development. Both the sense and the antisense messages are transcribed in D. pseudoobscura, but only the sense message (TRAP100) is transcribed in D. melanogaster complex species. Unlike the antisense message, the sense message is transcribed similarly in D. pseudoobscura males and females and in hybrids of D. pseudoobscura and D. persimilis. The high sequence similarity between distantly related species suggests that the sense message is functionally constrained within the genus. We speculate that the antisense transcript may have evolved a role in male-specific post-transcriptional regulation of TRAP100 in the D. pseudoobscura lineage and that its underexpression in sterile hybrid males may cause an overproduction of TRAP100 protein, possibly yielding deleterious effects.
Alternative Genetic Foundations for a Key Social Polymorphism in Fire Ants
Authors: Ross Kenneth G , Krieger Michael J B , Shoemaker D DeWayne 
Published: April 2021

AbstractLittle is known about the genetic foundations of colony social organization. One rare example in which a single major gene is implicated in the expression of alternative social organizations involves the presumed odorant-binding protein gene Gp-9 in fire ants. Specific amino acid substitutions in this gene invariably are associated with the expression of monogyny (single queen per colony) or polygyny (multiple queens per colony) in fire ant species of the Solenopsis richteri clade. These substitutions are hypothesized to alter the abilities of workers to recognize queens and thereby regulate their numbers in a colony. We examined whether these same substitutions underlie the monogyny/polygyny social polymorphism in the distantly related fire ant S. geminata. We found that Gp-9 coding region sequences are identical in the polygyne and monogyne forms of this species, disproving our hypothesis that one or a few specific amino acid replacements in the protein are necessary to induce transitions in social organization in fire ants. On the other hand, polygyne S. geminata differs genetically from the monogyne form in ways not mirrored in the two forms of S. invicta, a well-studied member of the S. richteri clade, supporting the conclusion that polygyny did not evolve via analogous routes in the two lineages. Specifically, polygyne S. geminata has lower genetic diversity and different gene frequencies than the monogyne form, suggesting that the polygyne form originated via a founder event from a local monogyne population. These comparative data suggest an alternative route to polygyny in S. geminata in which loss of allelic variation at genes encoding recognition cues has led to a breakdown in discrimination abilities and the consequent acceptance of multiple queens in colonies.
Nucleotide Variation of the Est-6 Gene Region in Natural Populations of Drosophila melanogaster
Authors: Balakirev Evgeniy S , Ayala Francisco J 
Published: April 2021

Abstract
We have investigated nucleotide polymorphism in the Est-6 gene region in four samples of Drosophila melanogaster derived from natural populations of East Africa (Zimbabwe), Europe (Spain), North America (California), and South America (Venezuela). There are two divergent sequence types in the North and South American samples, which are not perfectly (North America) or not at all (South America) associated with the Est-6 allozyme variation. Less pronounced or no sequence dimorphism occurs in the European and African samples, respectively. The level of nucleotide diversity is highest in the African sample, lower (and similar to each other) in the samples from Europe and North America, and lowest in the sample from South America. The extent of linkage disequilibrium is low in Africa (1.23% significant associations), but much higher in non-African populations (22.59, 21.45, and 37.68% in Europe, North America, and South America, respectively). Tests of neutrality with recombination are significant in non-African samples but not significant in the African sample. We propose that demographic history (bottleneck and admixture of genetically different populations) is the major factor shaping the nucleotide patterns in the Est-6 gene region. However, positive selection modifies the pattern: balanced selection creates elevated levels of nucleotide variation around functionally important (target) polymorphic sites (RsaI–/RsaI+ in the promoter region and F/S in the coding region) in both African and non-African samples; and directional selection, acting during the geographic expansion phase of D. melanogaster, creates an excess of very similar sequences (RsaI– and S allelic lineages, in the promoter and coding regions, respectively) in the non-African samples.
Hedgehog Signaling in the Drosophila Eye and Head: An Analysis of the Effects of Different patched Trans-heterozygotes
Authors: Thomas Chloe , Ingham Philip W 
Published: April 2021

Abstract
Characterization of different alleles of the Hedgehog receptor patched (ptc) indicates that they can be grouped into several classes. Most mutations result in complete loss of Ptc function. However, missense mutations located within the putative sterol-sensing domain (SSD) or C terminus of ptc encode antimorphic proteins that are unable to repress Smo activity and inhibit wild-type Ptc from doing so, but retain the ability to bind and sequester Hh. Analysis of the eye and head phenotypes of Drosophila melanogaster in various ptc/ptctuf1 heteroallelic combinations shows that these two classes of ptc allele can be easily distinguished by their eye phenotype, but not by their head phenotype. Adult eye size is inversely correlated with head vertex size, suggesting an alteration of cell fate within the eye-antennal disc. A balance between excess cell division and cell death in the mutant eye discs may also contribute to final eye size. In addition, contrary to results reported recently, the role of Hh signaling in the Drosophila head vertex appears to be primarily in patterning rather than in proliferation, with Ptc and Smo having opposing effects on formation of medial structures.
TheDrosophila melanogasterDNALigase IVGene Plays a Crucial Role in the Repair of Radiation-Induced DNA Double-Strand Breaks and Acts Synergistically WithRad54
Authors: Gorski Marcin M , Eeken Jan C J , de Jong Anja W M , Klink Ilse , Loos Marjan , Romeijn Ron J , van Veen Bert L , Mullenders Leon H , Ferro Wouter , Pastink Albert 
Published: April 2021

AbstractDNA Ligase IV has a crucial role in double-strand break (DSB) repair through nonhomologous end joining (NHEJ). Most notably, its inactivation leads to embryonic lethality in mammals. To elucidate the role of DNA Ligase IV (Lig4) in DSB repair in a multicellular lower eukaryote, we generated viable Lig4-deficient Drosophila strains by P-element-mediated mutagenesis. Embryos and larvae of mutant lines are hypersensitive to ionizing radiation but hardly so to methyl methanesulfonate (MMS) or the crosslinking agent cis-diamminedichloroplatinum (cisDDP). To determine the relative contribution of NHEJ and homologous recombination (HR) in Drosophila, Lig4; Rad54 double-mutant flies were generated. Survival studies demonstrated that both HR and NHEJ have a major role in DSB repair. The synergistic increase in sensitivity seen in the double mutant, in comparison with both single mutants, indicates that both pathways partially overlap. However, during the very first hours after fertilization NHEJ has a minor role in DSB repair after exposure to ionizing radiation. Throughout the first stages of embryogenesis of the fly, HR is the predominant pathway in DSB repair. At late stages of development NHEJ also becomes less important. The residual survival of double mutants after irradiation strongly suggests the existence of a third pathway for the repair of DSBs in Drosophila.
The Drosophila melanogaster importin α3 Locus Encodes an Essential Gene Required for the Development of Both Larval and Adult Tissues
Authors: Mason D Adam , Máthé Endre , Fleming Robert J , Goldfarb David S 
Published: April 2021

Abstract
The nuclear transport of classical nuclear localization signal (cNLS)-containing proteins is mediated by the cNLS receptor importin α. The conventional importin α gene family in metazoan animals is composed of three clades that are conserved between flies and mammals and are referred to here as α1, α2, and α3. In contrast, plants and fungi contain only α1 genes. In this study we report that Drosophila importin α3 is required for the development of both larval and adult tissues. Importin α3 mutant flies die around the transition from first to second instar larvae, and homozygous importin α3 mutant eyes are defective. The transition to second instar larvae was rescued with importin α1, α2, or α3 transgenes, indicating that Importin α3 is normally required at this stage for an activity shared by all three importin α's. In contrast, an α3-specific biochemical activity(s) of Importin α3 is probably required for development to adults and photoreceptor cell development, since only an importin α3 transgene rescued these processes. These results are consistent with the view that the importin α's have both overlapping and distinct functions and that their role in animal development involves the spatial and temporal control of their expression.
Wolbachia and Cytoplasmic Incompatibility in the CaliforniaCulex pipiensMosquito Species Complex: Parameter Estimates and Infection Dynamics in Natural Populations
Authors: Rasgon Jason L , Scott Thomas W 
Published: April 2021

AbstractBefore maternally inherited bacterial symbionts like Wolbachia, which cause cytoplasmic incompatibility (CI; reduced hatch rate) when infected males mate with uninfected females, can be used in a program to control vector-borne diseases it is essential to understand their dynamics of infection in natural arthropod vector populations. Our study had four goals: (1) quantify the number of Wolbachia strains circulating in the California Culex pipiens species complex, (2) investigate Wolbachia infection frequencies and distribution in natural California populations, (3) estimate the parameters that govern Wolbachia spread among Cx. pipiens under laboratory and field conditions, and (4) use these values to estimate equilibrium levels and compare predicted infection prevalence levels to those observed in nature. Strain-specific PCR, wsp gene sequencing, and crossing experiments indicated that a single Wolbachia strain infects Californian Cx. pipiens. Infection frequency was near or at fixation in all populations sampled for 2 years along a &gt;1000-km north-south transect. The combined statewide infection frequency was 99.4%. Incompatible crosses were 100% sterile under laboratory and field conditions. Sterility decreased negligibly with male age in the laboratory. Infection had no significant effect on female fecundity under laboratory or field conditions. Vertical transmission was &gt;99% in the laboratory and ∼98.6% in the field. Using field data, models predicted that Wolbachia will spread to fixation if infection exceeds an unstable equilibrium point above 1.4%. Our estimates accurately predicted infection frequencies in natural populations. If certain technical hurdles can be overcome, our data indicate that Wolbachia can invade vector populations as part of an applied transgenic strategy for vector-borne disease reduction.
Genetic Structure and Diversity Among Maize Inbred Lines as Inferred From DNA Microsatellites
Authors: Liu Kejun , Goodman Major , Muse Spencer , Smith J Stephen , Buckler Ed , Doebley John 
Published: April 2021

Abstract
Two hundred and sixty maize inbred lines, representative of the genetic diversity among essentially all public lines of importance to temperate breeding and many important tropical and subtropical lines, were assayed for polymorphism at 94 microsatellite loci. The 2039 alleles identified served as raw data for estimating genetic structure and diversity. A model-based clustering analysis placed the inbred lines in five clusters that correspond to major breeding groups plus a set of lines showing evidence of mixed origins. A “phylogenetic” tree was constructed to further assess the genetic structure of maize inbreds, showing good agreement with the pedigree information and the cluster analysis. Tropical and subtropical inbreds possess a greater number of alleles and greater gene diversity than their temperate counterparts. The temperate Stiff Stalk lines are on average the most divergent from all other inbred groups. Comparison of diversity in equivalent samples of inbreds and open-pollinated landraces revealed that maize inbreds capture &lt;80% of the alleles in the landraces, suggesting that landraces can provide additional genetic diversity for maize breeding. The contributions of four different segments of the landrace gene pool to each inbred group's gene pool were estimated using a novel likelihood-based model. The estimates are largely consistent with known histories of the inbreds and indicate that tropical highland germplasm is poorly represented in maize inbreds. Core sets of inbreds that capture maximal allelic richness were defined. These or similar core sets can be used for a variety of genetic applications in maize.
Recombination Can Evolve in Large Finite Populations Given Selection on Sufficient Loci
Authors: Iles Mark M , Walters Kevin , Cannings Chris 
Published: April 2021

Abstract
It is well known that an allele causing increased recombination is expected to proliferate as a result of genetic drift in a finite population undergoing selection, without requiring other mechanisms. This is supported by recent simulations apparently demonstrating that, in small populations, drift is more important than epistasis in increasing recombination, with this effect disappearing in larger finite populations. However, recent experimental evidence finds a greater advantage for recombination in larger populations. These results are reconciled by demonstrating through simulation without epistasis that for m loci recombination has an appreciable selective advantage over a range of population sizes (am, bm). bm increases steadily with m while am remains fairly static. Thus, however large the finite population, if selection acts on sufficiently many loci, an allele that increases recombination is selected for. We show that as selection acts on our finite population, recombination increases the variance in expected log fitness, causing indirect selection on a recombination-modifying locus. This effect is enhanced in those populations with more loci because the variance in phenotypic fitnesses in relation to the possible range will be smaller. Thus fixation of a particular haplotype is less likely to occur, increasing the advantage of recombination.