bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA Polymorphism, Haplotype Structure and Balancing Selection in the Leavenworthia PgiC Locus
Authors: Filatov Dmitry A , Charlesworth Deborah
Published: April 2021

A study of DNA polymorphism and divergence was conducted for the cytosolic phosphoglucose isomerase (PGI:E.C.5.3.1.9) gene of five species of the mustard genus Leavenworthia: Leavenworthia stylosa, L. alabamica, L. crassa, L. uniflora, and L. torulosa. Sequences of an internal 2.3-kb PgiC gene region spanning exons 6–16 were obtained from 14 L. stylosa plants from two natural populations and from one to several plants for each of the other species. The level of nucleotide polymorphism in L. stylosa PgiC gene was quite high (π = 0.051, θ = 0.052). Although recombination is estimated to be high in this locus, extensive haplotype structure was observed for the entire 2.3-kb region. The L. stylosa sequences fall into at least two groups, distinguished by the presence of several indels and nucleotide substitutions, and one of the three charge change nucleotide replacements within the region sequenced correlates with the haplotypes. The differences between the haplotypes are older than between the species, and the haplotypes are still segregating in at least two of five species studied. There is no evidence of recent or ancient population subdivision that could maintain distinct haplotypes. The age of the haplotypes and the results of Kelly's ZnS and Wall's B and Q tests with recombination suggest that the haplotypes are maintained due to balancing selection at or near this locus.
A Quantitative Model of the Relationship Between Phenotypic Variance and Heterozygosity at Marker Loci Under Partial Selfing
Authors: David Patrice
Published: April 2021

Negative relationships between allozyme heterozygosity and morphological variance have often been observed and interpreted as evidence for increased developmental stability in heterozygotes. However, inbreeding can also generate such relationships by decreasing heterozygosity at neutral loci and redistributing genetic variance at the same time. I here provide a quantitative genetic model of this process by analogy with heterozygosity-fitness relationships. Inbreeding generates negative heterozygosity-variance relationships irrespective of the genetic architecture of the trait. This holds for fitness traits as well as neutral traits, the effect being stronger for fitness traits under directional dominance or overdominance. The order of magnitude of heterozygosity-variance regressions is compatible with empirical data even with very low inbreeding. Although developmental stability effects cannot be excluded, inbreeding is a parsimonious explanation that should be seriously considered to explain correlations between heterozygosity and both mean and variance of phenotypes in natural populations.
Frequent Meiotic Recombination Between the Ends of Truncated Chromosome Fragments of Saccharomyces cerevisiae
Authors: Arbel Tamar , Shemesh Ronen , Simchen Giora
Published: April 2021

A single truncated chromosome fragment (TCF) in diploid cells undergoes frequent ectopic recombination during meiosis between markers located near the ends of the fragment. Tetrads produced by diploids with a single TCF show frequent loss of one of the two markers. This marker loss could result either from recombination of the TCF with one of the two copies of the chromosome from which it was derived or from ectopic recombination between the ends of the TCF. The former would result in shortening of a normal chromosome and lethality in one of the four spores. The high frequency of marker loss in tetrads with four viable spores supports recombination between the TCF ends as the main source of marker loss. Most of the spore colonies that display TCF marker loss contained a TCF with the same marker on both ends. Deletion of most of the pBR322 sequences distal to the marker at one of the subtelomeric regions of the TCF did not reduce the overall frequency of recombination between the ends, but affected the loss of one marker significantly more than the other. We suggest that the mechanism by which the duplication of one end marker and loss of the other occurs is based on association and recombination between the ends of the TCF.
SEL-5, A Serine/Threonine Kinase That Facilitates lin-12 Activity in Caenorhabditis elegans
Authors: Fares Hanna , Greenwald Iva
Published: April 2021

Ligands present on neighboring cells activate receptors of the LIN-12/Notch family by inducing a proteolytic cleavage event that releases the intracellular domain. Mutations that appear to eliminate sel-5 activity are able to suppress constitutive activity of lin-12(d) mutations that are point mutations in the extracellular domain of LIN-12, but cannot suppress lin-12(intra), the untethered intracellular domain. These results suggest that sel-5 acts prior to or during ligand-dependent release of the intracellular domain. In addition, sel-5 suppression of lin-12(d) mutations is tissue specific: loss of sel-5 activity can suppress defects in the anchor cell/ventral uterine precursor cell fate decision and a sex myoblast/coelomocyte decision, but cannot suppress defects in two different ventral hypodermal cell fate decisions in hermaphrodites and males. sel-5 encodes at least two proteins, from alternatively spliced mRNAs, that share an amino-terminal region and differ in the carboxy-terminal region. The amino-terminal region contains the hallmarks of a serine/threonine kinase domain, which is most similar to mammalian GAK1 and yeast Pak1p.
Cosuppression of I Transposon Activity in Drosophila by I-Containing Sense and Antisense Transgenes
Authors: Jensen Silke , Gassama Marie-Pierre , Heidmann Thierry
Published: April 2021

We have previously shown that the activity of functional I elements introduced into Drosophila devoid of such elements can be repressed by transgenes containing an internal nontranslatable part of the I element itself and that this repressing effect presents features characteristic of homology-dependent gene silencing or cosuppression. Here we show that transgenes containing a fragment of the I element in antisense orientation induce I-element silencing with the same characteristic features as the corresponding sense construct: namely, repression takes several generations to be fully established, with similar rates for sense and antisense constructs, and it is only maternally transmitted, with reversal of the effect through paternal transmission. We also show that transcription of the transgenes is necessary to produce the silencing effect and that repression can be maintained for at least one generation following elimination of the transgenes, thus strongly suggesting that a transgene product and not the transgene per se is the essential intermediate in the silencing effect. The data presented strongly support models in which the repressing effect of antisense transcripts involves the same mechanisms as cosuppression by sense constructs and emphasize the role of symmetrically acting nucleic acid structures in mediating repression.
Genetic Analyses of Visual Pigments of the Pigeon (Columba livia)
Authors: Kawamura Shoji , Blow Nathan S , Yokoyama Shozo
Published: April 2021

We isolated five classes of retinal opsin genes rh1Cl, rh2Cl, sws1Cl, sws2Cl, and lwsCl from the pigeon; these encode RH1Cl, RH2Cl, SWS1Cl, SWS2Cl, and LWSCl opsins, respectively. Upon binding to 11-cis-retinal, these opsins regenerate the corresponding photosensitive molecules, visual pigments. The absorbance spectra of visual pigments have a broad bell shape with the peak, being called λmax. Previously, the SWS1Cl opsin cDNA was isolated from the pigeon retinal RNA, expressed in cultured COS1 cells, reconstituted with 11-cis-retinal, and the λmax of the resulting SWS1Cl pigment was shown to be 393 nm. In this article, using the same methods, the λmax values of RH1Cl, RH2Cl, SWS2Cl, and LWSCl pigments were determined to be 502, 503, 448, and 559 nm, respectively. The pigeon is also known for its UV vision, detecting light at 320–380 nm. Being the only pigments that absorb light below 400 nm, the SWS1Cl pigments must mediate its UV vision. We also determined that a nonretinal PCl pigment in the pineal gland of the pigeon has a λmax value at 481 nm.
Long Inverted Repeats Are an At-Risk Motif for Recombination in Mammalian Cells
Authors: Waldman Alan S , Tran Hiep , Goldsmith Edie C , Resnick Michael A
Published: April 2021

Certain DNA sequence motifs and structures can promote genomic instability. We have explored instability induced in mouse cells by long inverted repeats (LIRs). A cassette was constructed containing a herpes simplex virus thymidine kinase (tk) gene into which was inserted an LIR composed of two inverted copies of a 1.1-kb yeast URA3 gene sequence separated by a 200-bp spacer sequence. The tk gene was introduced into the genome of mouse Ltk− fibroblasts either by itself or in conjunction with a closely linked tk gene that was disrupted by an 8-bp XhoI linker insertion; rates of intrachromosomal homologous recombination between the markers were determined. Recombination between the two tk alleles was stimulated 5-fold by the LIR, as compared to a long direct repeat (LDR) insert, resulting in nearly 10−5 events per cell per generation. Of the tk+ segregants recovered from LIR-containing cell lines, 14% arose from gene conversions that eliminated the LIR, as compared to 3% of the tk+ segregants from LDR cell lines, corresponding to a >20-fold increase in deletions at the LIR hotspot. Thus, an LIR, which is a common motif in mammalian genomes, is at risk for the stimulation of homologous recombination and possibly other genetic rearrangements.
Population Models of Genomic Imprinting. I. Differential Viability in the Sexes and the Analogy With Genetic Dominance
Authors: Anderson Richard J E , Spencer Hamish G
Published: April 2021

Many single-locus, two-allele selection models of genomic imprinting have been shown to reduce formally to one-locus Mendelian models with a modified parameter for genetic dominance. One exception is the model where selection at the imprinted locus affects the sexes differently. We present two models of maternal inactivation with differential viability in the sexes, one with complete inactivation, and the other with a partial penetrance for inactivation. We show that, provided dominance relations at the imprintable locus are the same in both sexes, a globally stable polymorphism exists for a range of viabilities that is independent of the penetrance of imprinting. The conditions for a polymorphism are the same as in previous models with differential viability in the sexes but without imprinting and in a model of the paternal X-inactivation system in marsupials. The model with incomplete inactivation is used to illustrate the analogy between imprinting and dominance by comparing equilibrium bifurcation plots for fixed values of dominance and penetrance. We also derive a single expression for the dominance parameter that leaves the frequency and stability of equilibria unchanged for all levels of inactivation. Although an imprinting model with sex differences does not formally reduce to a nonimprinting scheme, close theoretical parallels clearly exist.
A Comparison of Multilocus Clines Maintained by Environmental Adaptation or by Selection Against Hybrids
Authors: Kruuk L E B , Baird S J E , Gale K S , Barton N H
Published: April 2021

There has recently been considerable debate over the relative importance of selection against hybrids (“endogenous” selection) vs. adaptation to different environments (“exogenous”) in maintaining stable hybrid zones and hence in speciation. Single-locus models of endogenous and exogenous viability selection generate clines of similar shape, but the comparison has not been extended to multilocus systems, which are both quantitatively and qualitatively very different from the single-locus case. Here we develop an analytical multilocus model of differential adaptation across an environmental transition and compare it to previous heterozygote disadvantage models. We show that the shape of clines generated by exogenous selection is indistinguishable from that generated by endogenous selection. A stochastic simulation model is used to test the robustness of the analytical description to the effects of drift and strong selection, and confirms the prediction that pairwise linkage disequilibria are predominantly generated by migration. However, although analytical predictions for the width of clines maintained by heterozygote disadvantage fit well with the simulation results, those for environmental adaptation are consistently too narrow; reasons for the discrepancy are discussed. There is a smooth transition between a system in which a set of loci effectively act independently of each other and one in which they act as a single nonrecombining unit.
Effect of DNA Sequence Divergence on Homologous Recombination as Analyzed by a Random-Walk Model
Authors: Fujitani Youhei , Kobayashi Ichizo
Published: April 2021

A point connecting a pair of homologous regions of DNA duplexes moves along the homology in a reaction intermediate of the homologous recombination. Formulating this movement as a random walk, we were previously successful at explaining the dependence of the recombination frequency on the homology length. Recently, the dependence of the recombination frequency on the DNA sequence divergence in the homologous region was investigated experimentally; if the methyl-directed mismatch repair (MMR) system is active, the logarithm of the recombination frequency decreases very rapidly with an increase of the divergence in a low-divergence regime. Beyond this regime, the logarithm decreases slowly and linearly with the divergence. This “very rapid drop-off” is not observed when the MMR system is defective. In this article, we show that our random-walk model can explain these data in a straightforward way. When a connecting point encounters a diverged base pair, it is assumed to be destroyed with a probability that depends on the level of MMR activity.
Genetic Analysis of Transcription-Associated Mutation in Saccharomyces cerevisiae
Authors: Morey Natalie J , Greene Christopher N , Jinks-Robertson Sue
Published: April 2021

High levels of transcription are associated with elevated mutation rates in yeast, a phenomenon referred to as transcription-associated mutation (TAM). The transcription-associated increase in mutation rates was previously shown to be partially dependent on the Rev3p translesion bypass pathway, thus implicating DNA damage in TAM. In this study, we use reversion of a pGAL-driven lys2ΔBgl allele to further examine the genetic requirements of TAM. We find that TAM is increased by disruption of the nucleotide excision repair or recombination pathways. In contrast, elimination of base excision repair components has only modest effects on TAM. In addition to the genetic studies, the lys2ΔBgl reversion spectra of repair-proficient low and high transcription strains were obtained. In the low transcription spectrum, most of the frameshift events correspond to deletions of AT base pairs whereas in the high transcription strain, deletions of GC base pairs predominate. These results are discussed in terms of transcription and its role in DNA damage and repair.
Do-It-Yourself Statistics: A Computer-Assisted Likelihood Approach to Analysis of Data From Genetic Crosses
Authors: Robbins Leonard G
Published: April 2021

Graduate school programs in genetics have become so full that courses in statistics have often been eliminated. In addition, typical introductory statistics courses for the “statistics user” rather than the nascent statistician are laden with methods for analysis of measured variables while genetic data are most often discrete numbers. These courses are often seen by students and genetics professors alike as largely irrelevant cookbook courses. The powerful methods of likelihood analysis, although commonly employed in human genetics, are much less often used in other areas of genetics, even though current computational tools make this approach readily accessible. This article introduces the MLIKELY.PAS computer program and the logic of do-it-yourself maximum-likelihood statistics. The program itself, course materials, and expanded discussions of some examples that are only summarized here are available at http://www.unisi.it/ricerca/dip/bio_evol/sitomlikely/mlikely.html.
Expression of the Saccharomyces cerevisiae Gene YME1 in the Petite-Negative Yeast Schizosaccharomyces pombe Converts It to Petite-Positive
Authors: Kominsky Douglas J , Thorsness Peter E
Published: April 2021

Organisms that can grow without mitochondrial DNA are referred to as “petite-positive” and those that are inviable in the absence of mitochondrial DNA are termed “petite-negative.” The petite-positive yeast Saccharomyces cerevisiae can be converted to a petite-negative yeast by inactivation of Yme1p, an ATP- and metal-dependent protease associated with the inner mitochondrial membrane. Suppression of this yme1 phenotype can occur by virtue of dominant mutations in the α- and γ-subunits of mitochondrial ATP synthase. These mutations are similar or identical to those occurring in the same subunits of the same enzyme that converts the petite-negative yeast Kluyveromyces lactis to petite-positive. Expression of YME1 in the petite-negative yeast Schizosaccharomyces pombe converts this yeast to petite-positive. No sequence closely related to YME1 was found by DNA-blot hybridization to S. pombe or K. lactis genomic DNA, and no antigenically related proteins were found in mitochondrial extracts of S. pombe probed with antisera directed against Yme1p. Mutations that block the formation of the F1 component of mitochondrial ATP synthase are also petite-negative. Thus, the F1 complex has an essential activity in cells lacking mitochondrial DNA and Yme1p can mediate that activity, even in heterologous systems.
Linkage Analysis of Sex Determination in Bracon sp. Near hebetor (Hymenoptera: Braconidae)
Authors: Holloway Alisha K , Strand Michael R , Black William C , Antolin Michael F
Published: April 2021

To test whether sex determination in the parasitic wasp Bracon sp. near hebetor (Hymenoptera: Braconidae) is based upon a single locus or multiple loci, a linkage map was constructed using random amplified polymorphic DNA (RAPD) markers. The map includes 71 RAPD markers and one phenotypic marker, blonde. Sex was scored in a manner consistent with segregation of a single “sex locus” under complementary sex determination (CSD), which is common in haplodiploid Hymenoptera. Under haplodiploidy, males arise from unfertilized haploid eggs and females develop from fertilized diploid eggs. With CSD, females are heterozygous at the sex locus; diploids that are homozygous at the sex locus become diploid males, which are usually inviable or sterile. Ten linkage groups were formed at a minimum LOD of 3.0, with one small linkage group that included the sex locus. To locate other putative quantitative trait loci (QTL) for sex determination, sex was also treated as a binary threshold character. Several QTL were found after conducting permutation tests on the data, including one on linkage group I that corresponds to the major sex locus. One other QTL of smaller effect had a segregation pattern opposite to that expected under CSD, while another putative QTL showed a female-specific pattern consistent with either a sex-differentiating gene or a sex-specific deleterious mutation. Comparisons are made between this study and the indepth studies on sex determination and sex differentiation in the closely related B. hebetor.
Genotypic Stability, Segregation and Selection in Heteroplasmic Human Cell Lines Containing np 3243 Mutant mtDNA
Authors: Lehtinen Sanna K , Hance Nicole , El Meziane Abdellatif , Juhola M Katariina , Juhola K Martti I , Karhu Ritva , Spelbrink Johannes N , Holt Ian J , Jacobs Howard T
Published: April 2021

The mitochondrial genotype of heteroplasmic human cell lines containing the pathological np 3243 mtDNA mutation, plus or minus its suppressor at np 12300, has been followed over long periods in culture. Cell lines containing various different proportions of mutant mtDNA remained generally at a consistent, average heteroplasmy value over at least 30 wk of culture in nonselective media and exhibited minimal mitotic segregation, with a segregation number comparable with mtDNA copy number (≥1000). Growth in selective medium of cells at 99% np 3243 mutant mtDNA did, however, allow the isolation of clones with lower levels of the mutation, against a background of massive cell death. As a rare event, cell lines exhibited a sudden and dramatic diversification of heteroplasmy levels, accompanied by a shift in the average heteroplasmy level over a short period (<8 wk), indicating selection. One such episode was associated with a gain of chromosome 9. Analysis of respiratory phenotype and mitochondrial genotype of cell clones from such cultures revealed that stable heteroplasmy values were generally reestablished within a few weeks, in a reproducible but clone-specific fashion. This occurred independently of any straightforward phenotypic selection at the individual cell-clone level. Our findings are consistent with several alternate views of mtDNA organization in mammalian cells. One model that is supported by our data is that mtDNA is found in nucleoids containing many copies of the genome, which can themselves be heteroplasmic, and which are faithfully replicated. We interpret diversification and shifts of heteroplasmy level as resulting from a reorganization of such nucleoids, under nuclear genetic control. Abrupt remodeling of nucleoids in vivo would have major implications for understanding the developmental consequences of heteroplasmy, including mitochondrial disease phenotype and progression.
Extensive Genetic Interactions Between PRP8 and PRP17/CDC40, Two Yeast Genes Involved in Pre-mRNA Splicing and Cell Cycle Progression
Authors: Ben-Yehuda Sigal , Russell Caroline S , Dix Ian , Beggs Jean D , Kupiec Martin
Published: April 2021

Biochemical and genetic experiments have shown that the PRP17 gene of the yeast Saccharomyces cerevisiae encodes a protein that plays a role during the second catalytic step of the splicing reaction. It was found recently that PRP17 is identical to the cell division cycle CDC40 gene. cdc40 mutants arrest at the restrictive temperature after the completion of DNA replication. Although the PRP17/CDC40 gene product is essential only at elevated temperatures, splicing intermediates accumulate in prp17 mutants even at the permissive temperature. In this report we describe extensive genetic interactions between PRP17/CDC40 and the PRP8 gene. PRP8 encodes a highly conserved U5 snRNP protein required for spliceosome assembly and for both catalytic steps of the splicing reaction. We show that mutations in the PRP8 gene are able to suppress the temperature-sensitive growth phenotype and the splicing defect conferred by the absence of the Prp17 protein. In addition, these mutations are capable of suppressing certain alterations in the conserved PyAG trinucleotide at the 3′ splice junction, as detected by an ACT1-CUP1 splicing reporter system. Moreover, other PRP8 alleles exhibit synthetic lethality with the absence of Prp17p and show a reduced ability to splice an intron bearing an altered 3′ splice junction. On the basis of these findings, we propose a model for the mode of interaction between the Prp8 and Prp17 proteins during the second catalytic step of the splicing reaction.
The Product of the DNA Damage-Inducible Gene of Saccharomyces cerevisiae, DIN7, Specifically Functions in Mitochondria
Authors: Fikus Marta U , Mieczkowski Piotr A , Koprowski Piotr , Rytka Joanna , Śledziewska-Gójska Ewa , Cieśla Zygmunt
Published: April 2021

We reported previously that the product of the DNA damage-inducible gene of Saccharomyces cerevisiae, DIN7, belongs to a family of proteins that are involved in DNA repair and replication. The family includes S. cerevisiae proteins Rad2p and its human homolog XPGC, Rad27p and its mammalian homolog FEN-1, and Exonuclease I (Exo I). Here, we report that Din7p specifically affects metabolism of mitochondrial DNA (mtDNA). We have found that dun1 strains, defective in the transcriptional activation of the DNA damage-inducible genes RNR1, RNR2, and RNR3, exhibit an increased frequency in the formation of the mitochondrial petite (ρ−) mutants. This high frequency of petites arising in the dun1 strains is significantly reduced by the din7::URA3 allele. On the other hand, overproduction of Din7p from the DIN7 gene placed under control of the GAL1 promoter dramatically increases the frequency of petite formation and the frequency of mitochondrial mutations conferring resistance to erythromycin (Er). The frequencies of chromosomal mutations conferring resistance to canavanine (Canr) or adenine prototrophy (Ade+) are not affected by enhanced synthesis of Din7p. Experiments using Din7p fused to the green fluorescent protein (GFP) and cell fractionation experiments indicate that the protein is located in mitochondria. A possible mechanism that may be responsible for the decreased stability of the mitochondrial genome in S. cerevisiae cells with elevated levels of Din7p is discussed.
A Yeast Heterogeneous Nuclear Ribonucleoprotein Complex Associated With RNA Polymerase II
Authors: Conrad Nicholas K , Wilson Scott M , Steinmetz Eric J , Patturajan Meera , Brow David A , Swanson Maurice S , Corden Jeffry L
Published: April 2021

Recent evidence suggests a role for the carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II (pol II) in pre-mRNA processing. The yeast NRD1 gene encodes an essential RNA-binding protein that shares homology with mammalian CTD-binding proteins and is thought to regulate mRNA abundance by binding to a specific cis-acting element. The present work demonstrates genetic and physical interactions among Nrd1p, the pol II CTD, Nab3p, and the CTD kinase CTDK-I. Previous studies have shown that Nrd1p associates with the CTD of pol II in yeast two-hybrid assays via its CTD-interaction domain (CID). We show that nrd1 temperature-sensitive alleles are synthetically lethal with truncation of the CTD to 9 or 10 repeats. Nab3p, a yeast hnRNP, is a high-copy suppressor of some nrd1 temperature-sensitive alleles, interacts with Nrd1p in a yeast two-hybrid assay, and coimmunoprecipitates with Nrd1p. Temperature-sensitive alleles of NAB3 are suppressed by deletion of CTK1, a kinase that has been shown to phosphorylate the CTD and increase elongation efficiency in vitro. This set of genetic and physical interactions suggests a role for yeast RNA-binding proteins in transcriptional regulation.
Functions of Fission Yeast Orp2 in DNA Replication and Checkpoint Control
Authors: Kiely Joan , Haase S B , Russell Paul , Leatherwood Janet
Published: April 2021

orp2 is an essential gene of the fission yeast Schizosaccharomyces pombe with 22% identity to budding yeast ORC2. We isolated temperature-sensitive alleles of orp2 using a novel plasmid shuffle based on selection against thymidine kinase. Cells bearing the temperature-sensitive allele orp2-2 fail to complete DNA replication at a restrictive temperature and undergo cell cycle arrest. Cell cycle arrest depends on the checkpoint genes rad1 and rad3. Even when checkpoint functions are wild type, the orp2-2 mutation causes high rates of chromosome and plasmid loss. These phenotypes support the idea that Orp2 is a replication initiation factor. Selective spore germination allowed analysis of orp2 deletion mutants. These experiments showed that in the absence of orp2 function, cells proceed into mitosis despite a lack of DNA replication. This suggests either that the Orp2 protein is a part of the checkpoint machinery or more likely that DNA replication initiation is required to induce the replication checkpoint signal.
Fixation of Advantageous Alleles in Partially Self-Fertilizing Populations: The Effect of Different Selection Modes
Authors: Damgaard Christian
Published: April 2021

The expected fixation probability of an advantageous allele was examined in a partially self-fertilizing hermaphroditic plant species using the diffusion approximation. The selective advantage of the advantageous allele was assumed to be increased viability, increased fecundity, or an increase in male fitness. The mode of selection, as well as the selfing rate, the population size, and the dominance of the advantageous allele, affect the fixation probability of the allele. In general it was found that increases in selfing rate decrease the fixation probability under male sexual selection, increase fixation probability under fecundity selection, and increase when recessive and decrease when dominant under viability selection. In some cases the highest fixation probability of advantageous alleles under fecundity or under male sexual selection occurred at an intermediary selfing rate. The expected mean fixation times of the advantageous allele were also examined using the diffusion approximation.
Comparative Sequence Analysis and Patterns of Covariation in RNA Secondary Structures
Authors: Parsch John , Braverman John M , Stephan Wolfgang
Published: April 2021

A novel method of RNA secondary structure prediction based on a comparison of nucleotide sequences is described. This method correctly predicts nearly all evolutionarily conserved secondary structures of five different RNAs: tRNA, 5S rRNA, bacterial ribonuclease P (RNase P) RNA, eukaryotic small subunit rRNA, and the 3′ untranslated region (UTR) of the Drosophila bicoid (bcd) mRNA. Furthermore, covariations occurring in the helices of these conserved RNA structures are analyzed. Two physical parameters are found to be important determinants of the evolution of compensatory mutations: the length of a helix and the distance between base-pairing nucleotides. For the helices of bcd 3′ UTR mRNA and RNase P RNA, a positive correlation between the rate of compensatory evolution and helix length is found. The analysis of Drosophila bcd 3′ UTR mRNA further revealed that the rate of compensatory evolution decreases with the physical distance between base-pairing residues. This result is in qualitative agreement with Kimura's model of compensatory fitness interactions, which assumes that mutations occurring in RNA helices are individually deleterious but become neutral in appropriate combinations.
Three Subfamilies of Pheromone and Receptor Genes Generate Multiple B Mating Specificities in the Mushroom Coprinus cinereus
Authors: Halsall John R , Milner Michael J , Casselton Lorna A
Published: April 2021

The B mating type locus of the basidiomycete Coprinus cinereus encodes a large family of lipopeptide pheromones and their seven transmembrane domain receptors. Here we show that the B42 locus, like the previously described B6 locus, derives its unique specificity from nine multiallelic genes that are organized into three subgroups each comprising a receptor and two pheromone genes. We show that the three genes within each group are kept together as a functional unit by being embedded in an allele-specific DNA sequence. Using a combination of sequence analysis, Southern blotting, and DNA-mediated transformation with cloned genes, we demonstrate that different B loci may share alleles of one or two groups of genes. This is consistent with the prediction that the three subgroups of genes are functionally redundant and that it is the different combinations of their alleles that generate the multiple B mating specificities found in nature. The B42 locus was found to contain an additional gene, mfs1, that encodes a putative multidrug transporter belonging to the major facilitator family. In strains with other B mating specificities, this gene, whose functional significance was not established, lies in a region of shared homology flanking the B locus.
Balancing Selection at Closely Linked, Overdominant Loci in a Finite Population
Authors: Slatkin Montgomery
Published: April 2021

High levels of allelic diversity and strong linkage disequilibrium are found in the major histocompatibility (MHC) system in humans and other vertebrates. This article proposes several descriptive statistics that quantify the extent and pattern of strong linkage disequilibrium between pairs of highly polymorphic loci. It also develops an approximate analytic theory incorporating the effects of balancing selection, mutation, recombination, and genetic drift at two closely linked loci and compares the theoretical predictions with published surveys of the MHC class II loci, DQA1 and DQB1, in humans and nonhuman primates. The descriptive statistics proposed include the fraction of complementary haplotypes (haplotypes with D″ = 1), the fraction of excess haplotypes, and the numbers of alleles at each locus in complementary haplotypes with one or more alleles at the other locus. The model assumes the infinite alleles model of mutation and the symmetric overdominance model of selection. Analytic approximations in some cases are obtained in the strong selection, weak mutation (SSWM) limit introduced by J. Gillespie. The predictions of the approximate analysis are confirmed by simulation. Both the analytic theory and simulations show that relatively few haplotypes will be found when selection is strong and recombination is weak relative to genetic drift. The model can reproduce many of the observed patterns at DQA1 and DQB1 provided that the recombination rate is assumed to be very small.
Regulation of the Yeast INO1 Gene: The Products of the INO2, INO4 and OPI1 Regulatory Genes Are Not Required for Repression in Response to Inositol
Authors: Graves J Anthony , Henry Susan A
Published: April 2021

The ino2Δ, ino4Δ, opi1Δ, and sin3Δ mutations all affect expression of INO1, a structural gene for inositol-1-phosphate synthase. These same mutations affect other genes of phospholipid biosynthesis that, like INO1, contain the repeated element UASINO (consensus 5′ CATGTGAAAT 3′). In this study, we evaluated the effects of these four mutations, singly and in all possible combinations, on growth and expression of INO1. All strains carrying an ino2Δ or ino4Δ mutation, or both, failed to grow in medium lacking inositol. However, when grown in liquid culture in medium containing limiting amounts of inositol, the opi1Δ ino4Δ strain exhibited a level of INO1 expression comparable to, or higher than, the wild-type strain growing under the same conditions. Furthermore, INO1 expression in the opi1Δ ino4Δ strain was repressed in cells grown in medium fully supplemented with both inositol and choline. Similar results were obtained using the opi1Δ ino2Δ ino4Δ strain. Regulation of INO1 was also observed in the absence of the SIN3 gene product. Therefore, while Opi1p, Sin3p, and the Ino2p/Ino4p complex all affect the overall level of INO1 expression in an antagonistic manner, they do not appear to be responsible for transmitting the signal that leads to repression of INO1 in response to inositol. Various models for Opi1p function were tested and no evidence for binding of Opi1p to UASINO, or to Ino2p or Ino4p, was obtained.
The Origin of the Domestic Pig: Independent Domestication and Subsequent Introgression
Authors: Giuffra E , Kijas J M H , Amarger V , Carlborg Ö , Jeon J-T , Andersson L
Published: April 2021

The domestic pig originates from the Eurasian wild boar (Sus scrofa). We have sequenced mitochondrial DNA and nuclear genes from wild and domestic pigs from Asia and Europe. Clear evidence was obtained for domestication to have occurred independently from wild boar subspecies in Europe and Asia. The time since divergence of the ancestral forms was estimated at ~500,000 years, well before domestication ~9,000 years ago. Historical records indicate that Asian pigs were introduced into Europe during the 18th and early 19th centuries. We found molecular evidence for this introgression and the data indicated a hybrid origin of some major “European” pig breeds. The study is an advance in pig genetics and has important implications for the maintenance and utilization of genetic diversity in this livestock species.
Predicting Rates of Inbreeding in Populations Undergoing Selection
Authors: Woolliams John A , Bijma Piter
Published: April 2021

Tractable forms of predicting rates of inbreeding (ΔF) in selected populations with general indices, nonrandom mating, and overlapping generations were developed, with the principal results assuming a period of equilibrium in the selection process. An existing theorem concerning the relationship between squared long-term genetic contributions and rates of inbreeding was extended to nonrandom mating and to overlapping generations. ΔF was shown to be ~¼(1 − ω) times the expected sum of squared lifetime contributions, where ω is the deviation from Hardy-Weinberg proportions. This relationship cannot be used for prediction since it is based upon observed quantities. Therefore, the relationship was further developed to express ΔF in terms of expected long-term contributions that are conditional on a set of selective advantages that relate the selection processes in two consecutive generations and are predictable quantities. With random mating, if selected family sizes are assumed to be independent Poisson variables then the expected long-term contribution could be substituted for the observed, providing ¼ (since ω = 0) was increased to ½. Established theory was used to provide a correction term to account for deviations from the Poisson assumptions. The equations were successfully applied, using simple linear models, to the problem of predicting ΔF with sib indices in discrete generations since previously published solutions had proved complex.
Molecular Evolution of Odorant-Binding Protein Genes OS-E and OS-F in Drosophila
Authors: Hekmat-Scafe Daria S , Dorit Robert L , Carlson John R
Published: April 2021

The Drosophila olfactory genes OS-E and OS-F are members of a family of genes that encode insect odorant-binding proteins (OBPs). OBPs are believed to transport hydrophobic odorants through the aqueous fluid within olfactory sensilla to the underlying receptor proteins. The recent discovery of a large family of olfactory receptor genes in Drosophila raises new questions about the function, diversity, regulation, and evolution of the OBP family. We have investigated the OS-E and OS-F genes in a variety of Drosophila species. These studies highlight potential regions of functional significance in the OS-E and OS-F proteins, which may include a region required for interaction with receptor proteins. Our results suggest that the two genes arose by an ancient gene duplication, and that in some lineages, one or the other gene has been lost. In D. virilis, the OS-F gene shows a different spatial pattern of expression than in D. melanogaster. One of the OS-F introns shows a striking degree of conservation between the two species, and we identify a putative regulatory sequence within this intron. Finally, a phylogenetic analysis places both OS-E and OS-F within a large family of insect OBPs and OBP-like proteins.
Genetic Analysis of the Hybrid male rescue Locus of Drosophila
Authors: Orr H Allen , Irving Shannon
Published: April 2021

Several hybrid rescue mutations—alleles that restore the viability of normally lethal hybrids—have been discovered in Drosophila melanogaster and its relatives. Here we analyze one of these genes, Hybrid male rescue (Hmr), asking two questions about its role in hybrid inviability. (1) Does the wild-type allele from D. melanogaster (Hmrmel) cause hybrid embryonic inviability? (2) Does Hmrmel cause hybrid larval inviability? Our results show that the wild-type product of Hmr is neither necessary nor sufficient for hybrid embryonic inviability. Hmrmel does, however, appear to lower the viability of hybrid larvae. The data further suggest (though do not prove) that Hmrmel acts as a gain-of-function poison in hybrids. These findings support previous claims that hybrid embryonic and larval lethalities are genetically distinct and suggest that Hmrmel is at least one of the proximate causes of hybrid larval inviability.
Heritability of the Maternal Meiotic Drive System Linked toOmand High-Resolution Mapping of theResponderLocus in Mouse
Authors: de Villena Fernando Pardo-Manuel , de la Casa-Esperón Elena , Williams Jean W , Malette Jan-Michel , Rosa Michelle , Sapienza Carmen
Published: April 2021

ABSTRACT Matings between (C57BL/6 × DDK)F1 females and C57BL/6 males result in a significant excess of offspring inheriting maternal DDK alleles in the central region of mouse chromosome 11 due to meiotic drive at the second meiotic division. We have shown previously that the locus subject to selection is in the vicinity of D11Mit66, a marker closely linked to the Om locus that controls the preimplantation embryolethal phenotype known as the “DDK syndrome.” We have also shown that observation of meiotic drive in this system depends upon the genotype of the sire. Here we show that females that are heterozygous at Om retain the meiotic drive phenotype and define a 0.32-cM candidate interval for the Responder locus in this drive system. In addition, analysis of the inheritance of alleles at Om among the offspring of F1 intercrosses indicates that the effect of the sire is determined by the sperm genotype at Om or a locus linked to Om.
Codon-Substitution Models for Heterogeneous Selection Pressure at Amino Acid Sites
Authors: Yang Ziheng , Nielsen Rasmus , Goldman Nick , Pedersen Anne-Mette Krabbe
Published: April 2021

Comparison of relative fixation rates of synonymous (silent) and nonsynonymous (amino acid-altering) mutations provides a means for understanding the mechanisms of molecular sequence evolution. The nonsynonymous/synonymous rate ratio (ω = dN/dS) is an important indicator of selective pressure at the protein level, with ω = 1 meaning neutral mutations, ω < 1 purifying selection, and ω > 1 diversifying positive selection. Amino acid sites in a protein are expected to be under different selective pressures and have different underlying ω ratios. We develop models that account for heterogeneous ω ratios among amino acid sites and apply them to phylogenetic analyses of protein-coding DNA sequences. These models are useful for testing for adaptive molecular evolution and identifying amino acid sites under diversifying selection. Ten data sets of genes from nuclear, mitochondrial, and viral genomes are analyzed to estimate the distributions of ω among sites. In all data sets analyzed, the selective pressure indicated by the ω ratio is found to be highly heterogeneous among sites. Previously unsuspected Darwinian selection is detected in several genes in which the average ω ratio across sites is <1, but in which some sites are clearly under diversifying selection with ω > 1. Genes undergoing positive selection include the β-globin gene from vertebrates, mitochondrial protein-coding genes from hominoids, the hemagglutinin (HA) gene from human influenza virus A, and HIV-1 env, vif, and pol genes. Tests for the presence of positively selected sites and their subsequent identification appear quite robust to the specific distributional form assumed for ω and can be achieved using any of several models we implement. However, we encountered difficulties in estimating the precise distribution of ω among sites from real data sets.
Conidial Germination in Aspergillus nidulans Requires RAS Signaling and Protein Synthesis
Authors: Osherov Nir , May Gregory
Published: April 2021

The dormant spores of Aspergillus nidulans become competent for growth and nuclear division in a process called conidial germination. To analyze the molecular details of conidial germination, we developed a genetic screen in which we identified spore germination-deficient mutants that are blocked in this process at the restrictive temperature. These mutants defined eight genes, of which we identified five. Four of the five were directly involved in translation and protein folding, and the fifth showed a high degree of homology to a malonyl CoA synthetase. These results suggest that out of a wide array of processes occurring during conidial germination, translation is essential if germination is to proceed. We also show that conidia containing a mutant-activated form of rasA, the ras homologue in A. nidulans, germinate in the absence of an inducing carbon source, suggesting an important role for rasA signaling in conidial germination. Together these data suggest a model by which a carbon source activates a ras-dependent sensory mechanism, inducing translation and leading to conidial germination. This study shows that conidial germination in A. nidulans requires protein synthesis and that the initiation of translation is linked, through an as yet to be determined signaling cascade that includes rasA, to a carbon-source-sensing apparatus.
Analysis of maxillopedia Expression Pattern and Larval Cuticular Phenotype in Wild-Type and Mutant Tribolium
Authors: Shippy Teresa D , Guo Jianhua , Brown Susan J , Beeman Richard W , Denell Robin E
Published: April 2021

The Tribolium castaneum homeotic gene maxillopedia (mxp) is the ortholog of Drosophila proboscipedia (pb). Here we describe and classify available mxp alleles. Larvae lacking all mxp function die soon after hatching, exhibiting strong transformations of maxillary and labial palps to legs. Hypomorphic mxp alleles produce less severe transformations to leg. RNA interference with maxillopedia double-stranded RNA results in phenocopies of mxp mutant phenotypes ranging from partial to complete transformations. A number of gain-of-function (GOF) mxp alleles have been isolated based on transformations of adult antennae and/or legs toward palps. Finally, we have characterized the mxp expression pattern in wild-type and mutant embryos. In normal embryos, mxp is expressed in the maxillary and labial segments, whereas ectopic expression is observed in some GOF variants. Although mxp and Pb display very similar expression patterns, pb null embryos develop normally. The mxp mutant larval phenotype in Tribolium is consistent with the hypothesis that an ancestral pb-like gene had an embryonic function that was lost in the lineage leading to Drosophila.
Physical Mapping of Male Fertility and Meiotic Drive Quantitative Trait Loci in the Mouse t Complex Using Chromosome Deficiencies
Authors: Planchart Antonio , You Yun , Schimenti John C
Published: April 2021

The t complex spans 20 cM of the proximal region of mouse chromosome 17. A variant form, the t haplotype (t), exists at significant frequencies in wild mouse populations and is characterized by the presence of inversions that suppress recombination with wild-type (+) chromosomes. Transmission ratio distortion and sterility are associated with t and affect males only. It is hypothesized that these phenomena are caused by trans-acting distorter/sterility factors that interact with a responder locus (Tcrt) and that the distorter and sterility factors are the same because homozygosity of the distorters causes male sterility. One factor, Tcd1, was previously shown to be amorphic using a chromosome deletion. To overcome limitations imposed by recombination suppression, we used a series of deletions within the t complex in trans to t chromosomes to characterize the Tcd1 region. We find that the distorter activity of Tcd1 is distinct from a linked sterility factor, originally called tcs1. YACs mapped with respect to deletion breakpoints localize tcs1 to a 1.1-Mb interval flanked by D17Aus9 and Tctex1. We present evidence for the existence of multiple proximal t complex regions that exhibit distorter activity. These studies demonstrate the utility of chromosome deletions for complex trait analysis.