bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Method for Characterizing Replacement Rate Variation in Molecular Sequences: Application of the Fourier and Wavelet Models to Drosophila and Mammalian Proteins
Authors: Morozov Pavel , Sitnikova Tatyana , Churchill Gary , Ayala Francisco José , Rzhetsky Andrey 
Published: April 2021

Abstract
We propose models for describing replacement rate variation in genes and proteins, in which the profile of relative replacement rates along the length of a given sequence is defined as a function of the site number. We consider here two types of functions, one derived from the cosine Fourier series, and the other from discrete wavelet transforms. The number of parameters used for characterizing the substitution rates along the sequences can be flexibly changed and in their most parameter-rich versions, both Fourier and wavelet models become equivalent to the unrestricted-rates model, in which each site of a sequence alignment evolves at a unique rate. When applied to a few real data sets, the new models appeared to fit data better than the discrete gamma model when compared with the Akaike information criterion and the likelihood-ratio test, although the parametric bootstrap version of the Cox test performed for one of the data sets indicated that the difference in likelihoods between the two models is not significant. The new models are applicable to testing biological hypotheses such as the statistical identity of rate variation profiles among homologous protein families. These models are also useful for determining regions in genes and proteins that evolve significantly faster or slower than the sequence average. We illustrate the application of the new method by analyzing human immunoglobulin and Drosophilid alcohol dehydrogenase sequences.
Sequence and Structural Diversity of the S Locus Genes From Different Lines With the Same Self-Recognition Specificities in Brassica oleracea
Authors: Kusaba Makoto , Matsushita Masanori , Okazaki Keiichi , Satta Yoko , Nishio Takeshi 
Published: April 2021

Abstract
Self-incompatibility (SI) is a mechanism for preventing self-fertilization in flowering plants. In Brassica, it is controlled by a single multi-allelic locus, S, and it is believed that two highly polymorphic genes in the S locus, SLG and SRK, play central roles in self-recognition in stigmas. SRK is a putative receptor protein kinase, whose extracellular domain exhibits high similarity to SLG. We analyzed two pairs of lines showing cross-incompatibility (S2 and S2-b; S13 and S13-b). In S2 and S2-b, SRKs were more highly conserved than SLGs. This was also the case with S13 and S13-b. This suggests that the SRKs of different lines must be conserved for the lines to have the same self-recognition specificity. In particular, SLG2-b showed only 88.5% identity to SLG2, which is comparable to that between the SLGs of different S haplotypes, while SRK2-b showed 97.3% identity to SRK2 in the S domain. These findings suggest that the SLGs in these S haplotypes are not important for self-recognition in SI.
Palindromes as Substrates for Multiple Pathways of Recombination in Escherichia coli
Authors: Cromie Gareth A , Millar Catherine B , Schmidt Kristina H , Leach David R F 
Published: April 2021

Abstract
A 246-bp imperfect palindrome has the potential to form hairpin structures in single-stranded DNA during replication. Genetic evidence suggests that these structures are converted to double-strand breaks by the SbcCD nuclease and that the double-strand breaks are repaired by recombination. We investigated the role of a range of recombination mutations on the viability of cells containing this palindrome. The palindrome was introduced into the Escherichia coli chromosome by phage λ lysogenization. This was done in both wt and sbcC backgrounds. Repair of the SbcCD-induced double-strand breaks requires a large number of proteins, including the components of both the RecB and RecF pathways. Repair does not involve PriA-dependent replication fork restart, which suggests that the double-strand break occurs after the replication fork has passed the palindrome. In the absence of SbcCD, recombination still occurs, probably using a gap substrate. This process is also PriA independent, suggesting that there is no collapse of the replication fork. In the absence of RecA, the RecQ helicase is required for palindrome viability in a sbcC mutant, suggesting that a helicase-dependent pathway exists to allow replicative bypass of secondary structures.
Comparative Genomics, Marker Density and Statistical Analysis of Chromosome Rearrangements
Authors: Schoen Daniel J 
Published: April 2021

Abstract
Estimates of the number of chromosomal breakpoints that have arisen (e.g., by translocation and inversion) in the evolutionary past between two species and their common ancestor can be made by comparing map positions of marker loci. Statistical methods for doing so are based on a random-breakage model of chromosomal rearrangement. The model treats all modes of chromosome rearrangement alike, and it assumes that chromosome boundaries and breakpoints are distributed randomly along a single genomic interval. Here we use simulation and numerical analysis to test the validity of these model assumptions. Mean estimates of numbers of breakpoints are close to those expected under the random-breakage model when marker density is high relative to the amount of chromosomal rearrangement and when rearrangements occur by translocation alone. But when marker density is low relative to the number of chromosomes, and when rearrangements occur by both translocation and inversion, the number of breakpoints is underestimated. The underestimate arises because rearranged segments may contain markers, yet the rearranged segments may, nevertheless, be undetected. Variances of the estimate of numbers of breakpoints decrease rapidly as markers are added to the comparative maps, but are less influenced by the number or type of chromosomal rearrangement separating the species. Variances obtained with simulated genomes comprised of chromosomes of equal length are substantially lower than those obtained when chromosome size is unconstrained. Statistical power for detecting heterogeneity in the rate of chromosomal rearrangement is also investigated. Results are interpreted with respect to the amount of marker information required to make accurate inferences about chromosomal evolution.
Tetrahymena Micronuclear Genome Mapping: A High-Resolution Meiotic Map of Chromosome 1L
Authors: Wickert Steve , Orias Eduardo 
Published: April 2021

Abstract
The ciliate Tetrahymena thermophila is a useful model organism that combines diverse experimental advantages with powerful capabilities for genetic manipulation. The genetics of Tetrahymena are especially rich among eukaryotic cells, because it possesses two distinct but related nuclear genomes within one cytoplasm, contained separately in the micronucleus (MIC) and the macronucleus (MAC). In an effort to advance fulfillment of Tetrahymena's potential as a genetic system, we are mapping both genomes and investigating the correspondence between them. With the latter goal especially in mind, we report here a high-resolution meiotic linkage map of the left arm of chromosome 1, one of Tetrahymena's five chromosomes. The map consists of 40 markers, with an average spacing of 2.3 cM in the Haldane function and a total length of 88.6 cM. This study represents the first mapping of any large region of the Tetrahymena genome that has been done at this level of detail. Results of a parallel mapping effort in the macronucleus, and the correspondence between the two genomes, can be found in this issue as a companion to this article.
Tetrahymena Macronuclear Genome Mapping: Colinearity of Macronuclear Coassortment Groups and the Micronuclear Map on Chromosome 1L
Authors: Wickert Steve , Nangle Leslie , Shevel Steve , Orias Eduardo 
Published: April 2021

Abstract
The genetics of the ciliate Tetrahymena thermophila are richer than for most other eukaryotic cells, because Tetrahymena possesses two genomes: a germline (micronuclear) genome that follows a Mendelian model of genetic transmission and a somatic (macronuclear) genome, derived from the micronuclear genome by fragmentation, which follows a different genetic transmission model called phenotypic assortment. While genetic markers in the micronucleus fall into classical linkage groups under meiotic recombination and segregation, the same markers in the macronucleus fall into coassortment groups (CAGs) under phenotypic assortment by the random distribution of MAC chromosome pieces. We set out to determine whether genomic mapping in the macronucleus by genetic means is feasible. To investigate the relationship between the micronuclear map and coassortment groups, we systematically placed into CAGs all of the markers lying on chromosome 1L that are also found in the macronucleus. Sixteen CAGs were identified, 7 of which contain at least two loci. We have concluded that CAGs represent a fundamental genetic feature of the MAC. The MIC and MAC maps on 1L are colinear; that is, CAGs consist exclusively of markers that map to a continuous segment in a given region of the micronuclear map, with no intervening markers from other CAGs. These findings provide a solid foundation for exploiting the MAC chromosome pieces to build a physical map of the Tetrahymena genome.
Multigeneration Maximum-Likelihood Analysis Applied to Mutation-Accumulation Experiments in Caenorhabditis elegans
Authors: Keightley Peter D , Bataillon Thomas M 
Published: April 2021

Abstract
We develop a maximum-likelihood (ML) approach to estimate genomic mutation rates (U) and average homozygous mutation effects (s) from mutation-accumulation (MA) experiments in which phenotypic assays are carried out in several generations. We use simulations to compare the procedure's performance with the method of moments traditionally used to analyze MA data. Similar precision is obtained if mutation effects are small relative to the environmental standard deviation, but ML can give estimates of mutation parameters that have lower sampling variances than those obtained by the method of moments if mutations with large effects have accumulated. The inclusion of data from intermediate generations may improve the precision. We analyze life-history trait data from two Caenorhabditis elegans MA experiments. Under a model with equal mutation effects, the two experiments provide similar estimates for U of ~0.005 per haploid, averaged over traits. Estimates of s are more divergent and average at −0.51 and −0.13 in the two studies. Detailed analysis shows that changes of mean and variance of genetic values of MA lines in both C. elegans experiments are dominated by mutations with large effects, but the analysis does not rule out the presence of a large class of deleterious mutations with very small effects.
Detecting Ancient Admixture in Humans Using Sequence Polymorphism Data
Authors: Wall Jeffrey D 
Published: April 2021

Abstract
A debate of long-standing interest in human evolution centers around whether archaic human populations (such as the Neanderthals) have contributed to the modern gene pool. A model of ancient population structure with recent mixing is introduced, and it is determined how much information (i.e., sequence data from how many unlinked nuclear loci) would be necessary to distinguish between different demographic scenarios. It is found that ~50–100 loci are necessary if plausible parameter estimates are used. There are not enough data available at the present to support either the “single origin” or the “multiregional” model of modern human evolution. However, this information should be available in a few years.
Mutation Frequency and Specificity With Age in Liver, Bladder and Brain of lacI Transgenic Mice
Authors: Stuart Gregory R , Oda Yoshimitsu , de Boer Johan G , Glickman Barry W 
Published: April 2021

Abstract
Mutation frequency and specificity were determined as a function of age in nuclear DNA from liver, bladder, and brain of Big Blue lacI transgenic mice aged 1.5–25 months. Mutations accumulated with age in liver and accumulated more rapidly in bladder. In the brain a small initial increase in mutation frequency was observed in young animals; however, no further increase was observed in adult mice. To investigate the origin of mutations, the mutational spectra for each tissue and age were determined. DNA sequence analysis of mutant lacI transgenes revealed no significant changes in mutational specificity in any tissue at any age. The spectra of mutations found in aging animals were identical to those in younger animals, suggesting that they originated from a common set of DNA lesions manifested during DNA replication. The data also indicated that there were no significant age-related mutational changes due to oxidative damage, or errors resulting from either changes in the fidelity of DNA polymerase or the efficiency of DNA repair. Hence, no evidence was found to support hypotheses that predict that oxidative damage or accumulation of errors in nuclear DNA contributes significantly to the aging process, at least in these three somatic tissues.
Evidence That Stationary-Phase Hypermutation in the Escherichia coli Chromosome Is Promoted by Recombination
Authors: Bull Harold J , McKenzie Gregory J , Hastings P J , Rosenberg Susan M 
Published: April 2021

Abstract
Adaptive (or stationary-phase) mutation is a group of phenomena in which mutations appear to occur more often when selected than when not. They may represent cellular responses to the environment in which the genome is altered to allow survival. The best-characterized assay system and mechanism is reversion of a lac allele on an F′ sex plasmid in Escherichia coli, in which the stationary-phase mutability requires homologous recombination functions. A key issue has concerned whether the recombination-dependent mutation mechanism is F′ specific or is general. Hypermutation of chromosomal genes occurs in association with adaptive Lac+ mutation. Here we present evidence that the chromosomal hypermutation is promoted by recombination. Hyperrecombinagenic recD cells show elevated chromosomal hypermutation. Further, recG mutation, which promotes accumulation of recombination intermediates proposed to prime replication and mutation, also stimulates chromosomal hypermutation. The coincident mutations at lac (on the F′) and chromosomal genes behave as independent events, whereas coincident mutations at lac and other F-linked sites do not. This implies that transient covalent linkage of F′ and chromosomal DNA (Hfr formation) does not underlie chromosomal mutation. The data suggest that recombinational stationary-phase mutation occurs in the bacterial chromosome and thus can be a general strategy for programmed genetic change.
A Yeast taf17 Mutant Requires the Swi6 Transcriptional Activator for Viability and Shows Defects in Cell Cycle-Regulated Transcription
Authors: Macpherson Neil , Measday Vivien , Moore Lynda , Andrews Brenda 
Published: April 2021

Abstract
In Saccharomyces cerevisiae, the Swi6 protein is a component of two transcription factors, SBF and MBF, that promote expression of a large group of genes in the late G1 phase of the cell cycle. Although SBF is required for cell viability, SWI6 is not an essential gene. We performed a synthetic lethal screen to identify genes required for viability in the absence of SWI6 and identified 10 complementation groups of swi6-dependent lethal mutants, designated SLM1 through SLM10. We were most interested in mutants showing a cell cycle arrest phenotype; both slm7-1 swi6Δ and slm8-1 swi6Δ double mutants accumulated as large, unbudded cells with increased 1N DNA content and showed a temperature-sensitive growth arrest in the presence of Swi6. Analysis of the transcript levels of cell cycle-regulated genes in slm7-1 SWI6 mutant strains at the permissive temperature revealed defects in regulation of a subset of cyclin-encoding genes. Complementation and allelism tests showed that SLM7 is allelic with the TAF17 gene, which encodes a histone-like component of the general transcription factor TFIID and the SAGA histone acetyltransferase complex. Sequencing showed that the slm7-1 allele of TAF17 is predicted to encode a version of Taf17 that is truncated within a highly conserved region. The cell cycle and transcriptional defects caused by taf17slm7-1 are consistent with the role of TAFIIs as modulators of transcriptional activation and may reflect a role for TAF17 in regulating activation by SBF and MBF.
The Size and Internal Structure of a Heterochromatic Block Determine Its Ability to Induce Position Effect Variegation in Drosophila melanogaster
Authors: Tolchkov Eugene V , Rasheva Vanya I , Bonaccorsi Silvia , Westphal Thomas , Gvozdev Vladimir A 
Published: April 2021

Abstract
In the In(1LR)pn2a rearrangement, the 1A-2E euchromatic segment is transposed to the vicinity of X heterochromatin (Xh), resulting in position effect variegation (PEV) of the genes in the 2BE region. Practically the whole X-linked heterochromatin is situated adjacent to variegated euchromatic genes. Secondary rearrangements showing weakening or reversion of PEV were obtained by irradiation of the In(1LR)pn2a. These rearrangements demonstrate a positive correlation between the strength of PEV of the wapl locus and the sizes of the adjacent heterochromatic blocks carrying the centromere. The smallest PEV-inducing fragment consists of a block corresponding to ~10% of Xh and containing the entire XR, the centromere, and a very proximal portion of XL heterochromatin. Heterochromatic blocks retaining the entire XR near the 2E region, but lacking the centromere, show no PEV. Reversion of PEV was also observed as a result of an internal rearrangement of the Xh blocks where the centromere is moved away from the eu-heterochromatin boundary but the amount of X heterochromatin remaining adjacent to 2E is unchanged. We propose a primary role of the X pericentromeric region in PEV induction and an enhancing effect of the other blocks, positively correlated with their size.
Paramutation Alters Regulatory Control of the Maize pl Locus
Authors: Hollick Jay B , Patterson Garth I , Asmundsson Ingrid M , Chandler Vicki L 
Published: April 2021

Abstract
The maize purple plant (pl) locus encodes a transcription factor required for anthocyanin pigment synthesis in vegetative and floral tissues. The strongly expressed Pl-Rhoades (Pl-Rh) allele is unstable, spontaneously changing to weaker expression states (Pl′) at low frequencies and exclusively changing to Pl′ in Pl′/Pl-Rh heterozygotes. The weakly expressed Pl′ state is mitotically and meiotically stable, yet reversible. This type of allele-dependent, heritable alteration of gene control is called paramutation. Expression studies herein demonstrate that visible differences in anthocyanin pigment levels mirror pl RNA abundance and that pl paramutation is associated with reduced transcription of the pl gene. This transcriptional alteration is accompanied by acquisition of light-dependent regulation. Restriction endonuclease mapping indicates that these changes in pl gene regulation are not associated with detectable DNA alterations or with extensive changes in cytosine methylation patterns. Genetic tests show that Pl-Blotched (Pl-Bh), a structurally similar pl allele encoding an identical pl RNA and PL protein, does not participate in pl paramutation. This result suggests that if cis-acting sequences are required for pl paramutation they are distinct from the protein coding and immediately adjacent regions. A model is discussed in which pl paramutation results in heritable changes of chromatin structure that fundamentally alter regulatory interactions occurring during plant development.
Offsetting Effects of Wolbachia Infection and Heat Shock on Sperm Production in Drosophila simulans: Analyses of Fecundity, Fertility and Accessory Gland Proteins
Authors: Snook Rhonda R , Cleland Sophia Y , Wolfner Mariana F , Karr Timothy L 
Published: April 2021

Abstract
Infection in Drosophila simulans with the endocellular symbiont Wolbachia pipientis results in egg lethality caused by failure to properly initiate diploid development (cytoplasmic incompatibility, CI). The relationship between Wolbachia infection and reproductive factors influencing male fitness has not been well examined. Here we compare infected and uninfected strains of D. simulans for (1) sperm production, (2) male fertility, and (3) the transfer and processing of two accessory gland proteins, Acp26Aa or Acp36De. Infected males produced significantly fewer sperm cysts than uninfected males over the first 10 days of adult life, and infected males, under varied mating conditions, had lower fertility compared to uninfected males. This fertility effect was due to neither differences between infected and uninfected males in the transfer and subsequent processing of accessory gland proteins by females nor to the presence of Wolbachia in mature sperm. We found that heat shock, which is known to decrease CI expression, increases sperm production to a greater extent in infected compared to uninfected males, suggesting a possible link between sperm production and heat shock. Given these results, the roles Wolbachia and heat shock play in mediating male gamete production may be important parameters for understanding the dynamics of infection in natural populations.
A STE12 Homolog Is Required for Mating but Dispensable for Filamentation in Candida lusitaniae
Authors: Young Laura Y , Lorenz Michael C , Heitman Joseph 
Published: April 2021

Abstract
Candida lusitaniae is a dimorphic yeast that is emerging as an opportunistic fungal pathogen. In contrast to Candida albicans, which is diploid and asexual, C. lusitaniae has been reported to have a sexual cycle. We have employed genetic approaches to demonstrate that C. lusitaniae is haploid and has a sexual cycle involving mating between MATa and MATα cells under nutrient deprivation conditions. By degenerate PCR, we identified a C. lusitaniae homolog (Cls12) of the Ste12 transcription factor that regulates mating, filamentation, and virulence in Saccharomyces cerevisiae, C. albicans, and Cryptococcus neoformans. Comparison of the CLS12 DNA and protein sequences to other STE12 homologs and transformation experiments with selectable markers from S. cerevisiae (URA3, KanMX, HphMX) and C. albicans (CaURA3) provide evidence that the CUG codon encodes serine instead of leucine in C. lusitaniae, as is also the case in C. albicans. The C. lusitaniae CLS12 gene was disrupted by biolistic transformation and homologous recombination. C. lusitaniae cls12 mutant strains were sterile but had no defect in filamentous growth. Our findings reveal both conserved and divergent roles for the C. lusitaniae STE12 homolog in regulating differentiation of this emerging fungal pathogen.