Comparative Analysis of Bam and Bgcn Sequences and Predicted Protein Structural Evolution.

The protein encoded by the gene ( ) plays an essential role in early gametogenesis by complexing with the gene product of ( ) to promote germline stem cell daughter differentiation in males and females. Here, we compared the AlphaFold2 and AlphaFold Multimer predicted structures of Bam protein and the Bam:Bgcn protein complex between , where is necessary in gametogenesis to that in , where it is not. Despite significant sequence divergence, we find very little evidence of significant structural differences in high confidence regions of the structures across the four species.

Non-ovarian titer correlates with fertility rescue of a hypomorph.

( ) is an essential gene that regulates germline stem cell maintenance and germline stem cell daughter cell differentiation in . When is partially functional (hypomorphic), the introduction of rescues the mutant fertility phenotype that would otherwise result in partial sterility. Infection by different variants results in differential rescue of the hypomorph fertility phenotype.

Wolbachia infection at least partially rescues the fertility and ovary defects of several new Drosophila melanogaster bag of marbles protein-coding mutants.

The D. melanogaster protein coding gene bag of marbles (bam) plays a key role in early male and female reproduction by forming complexes with partner proteins to promote differentiation in gametogenesis. Like another germline gene, Sex lethal, bam genetically interacts with the endosymbiont Wolbachia, as Wolbachia rescues the reduced fertility of a bam hypomorphic mutant.

infection at least partially rescues the fertility and ovary defects of several new protein-coding mutants.

Unlabelled: The protein coding gene ( ) plays a key role in early male and female reproduction by forming complexes with partner proteins to promote differentiation in gametogenesis. Like another germline gene, , genetically interacts with the endosymbiont , as rescues the reduced fertility of a hypomorphic mutant. Here, we explored the specificity of the interaction by generating 22 new mutants, with ten mutants displaying fertility defects.

Evolution under a model of functionally buffered deleterious mutations can lead to positive selection in protein-coding genes.

Selective pressures on DNA sequences often result in departures from neutral evolution that can be captured by the McDonald-Kreitman (MK) test. However, the nature of such selective forces often remains unknown to experimentalists. Amino acid fixations driven by natural selection in protein-coding genes are commonly associated with a genetic arms race or changing biological purposes, leading to proteins with new functionality.

genetically interacts with the germline stem cell gene in male .

The bacterial endosymbiont manipulates reproduction of its arthropod hosts to promote its own maternal vertical transmission. In female , has been shown to genetically interact with three key reproductive genes ( ( ) and , as it rescues the reduced female fertility or fecundity phenotype seen in partial loss-of-function mutants of these genes Here, we show that also partially rescues male fertility in carrying a new, largely sterile allele when in a null genetic background. This finding shows that the molecular mechanism of 's influence on its hosts' reproduction involves interaction with genes in males as well as females, at least in .

Functional Divergence of the bag-of-marbles Gene in the Drosophila melanogaster Species Group.

In Drosophila melanogaster, a key germline stem cell (GSC) differentiation factor, bag of marbles (bam) shows rapid bursts of amino acid fixations between sibling species D. melanogaster and Drosophila simulans, but not in the outgroup species Drosophila ananassae. Here, we test the null hypothesis that bam's differentiation function is conserved between D.

Recommendations for improving statistical inference in population genomics.

The field of population genomics has grown rapidly in response to the recent advent of affordable, large-scale sequencing technologies. As opposed to the situation during the majority of the 20th century, in which the development of theoretical and statistical population genetic insights outpaced the generation of data to which they could be applied, genomic data are now being produced at a far greater rate than they can be meaningfully analyzed and interpreted. With this wealth of data has come a tendency to focus on fitting specific (and often rather idiosyncratic) models to data, at the expense of a careful exploration of the range of possible underlying evolutionary processes.

Molecular population genetics of Sex-lethal (Sxl) in the Drosophila melanogaster species group: a locus that genetically interacts with Wolbachia pipientis in Drosophila melanogaster.

Sex-lethal (Sxl) is the sex determination switch in Drosophila, and also plays a critical role in germ-line stem cell daughter differentiation in Drosophila melanogaster. Three female-sterile alleles at Sxl in D. melanogaster were previously shown to genetically interact to varying degrees with the maternally inherited endosymbiont Wolbachia pipientis.

Diverse wMel variants of Wolbachia pipientis differentially rescue fertility and cytological defects of the bag of marbles partial loss of function mutation in Drosophila melanogaster.

In Drosophila melanogaster, the maternally inherited endosymbiont Wolbachia pipientis interacts with germline stem cell genes during oogenesis. One such gene, bag of marbles (bam) is the key switch for differentiation and also shows signals of adaptive evolution for protein diversification. These observations have led us to hypothesize that W.

Baker's Yeast Clinical Isolates Provide a Model for How Pathogenic Yeasts Adapt to Stress.

Global outbreaks of drug-resistant fungi such as Candida auris are thought to be due at least in part to excessive use of antifungal drugs. Baker's yeast Saccharomyces cerevisiae has gained importance as an emerging opportunistic fungal pathogen that can cause infections in immunocompromised patients. Analyses of over 1000 S.

The importance of the Neutral Theory in 1968 and 50 years on: A response to Kern and Hahn 2018.

A recent article reassessing the Neutral Theory of Molecular Evolution claims that it is no longer as important as is widely believed. The authors argue that "the neutral theory was supported by unreliable theoretical and empirical evidence from the beginning, and that in light of modern, genome-scale data, we can firmly reject its universality." Claiming that "the neutral theory has been overwhelmingly rejected," they propose instead that natural selection is the major force shaping both between-species divergence and within-species variation.

Incompatibilities in Mismatch Repair Genes Contribute to a Wide Range of Mutation Rates in Human Isolates of Baker's Yeast.

Laboratory baker's yeast strains bearing an incompatible combination of and mismatch repair alleles are mutators that can adapt more rapidly to stress, but do so at the cost of long-term fitness. We identified 18 baker's yeast isolates from 1011 surveyed that contain the incompatible genotype in a heterozygous state. Surprisingly, the incompatible combination from two human clinical heterozygous diploid isolates, YJS5845 and YJS5885, contain the exact (S288c-derived) and (SK1-derived) open reading frames originally shown to confer incompatibility.

Mismatch Repair Incompatibilities in Diverse Yeast Populations.

An elevated mutation rate can provide cells with a source of mutations to adapt to changing environments. We identified a negative epistatic interaction involving naturally occurring variants in the and mismatch repair (MMR) genes of We hypothesized that this MMR incompatibility, created through mating between divergent , yields mutator progeny that can rapidly but transiently adapt to an environmental stress. Here we analyzed the and genes across 1010 natural isolates spanning a wide range of ecological sources (tree exudates, , fruits, and various fermentation and clinical isolates) and geographical sources (Europe, America, Africa, and Asia).

Recent and Long-Term Selection Across Synonymous Sites in Drosophila ananassae.

In Drosophila, many studies have examined the short- or long-term evolution occurring across synonymous sites. Few, however, have examined both the recent and long-term evolution to gain a complete view of this selection. Here we have analyzed Drosophila ananassae DNA polymorphism and divergence data using several different methods, and have identified evidence of positive selection favoring preferred codons in both recent and long-term evolutionary time scale.

Inversions and adaptation to the plant toxin ouabain shape DNA sequence variation within and between chromosomal inversions of Drosophila subobscura.

Adaptation is defined as an evolutionary process allowing organisms to succeed in certain habitats or conditions. Chromosomal inversions have the potential to be key in the adaptation processes, since they can contribute to the maintenance of favoured combinations of adaptive alleles through reduced recombination between individuals carrying different inversions. We have analysed six genes (Pif1A, Abi, Sqd, Yrt, Atpα and Fmr1), located inside and outside three inversions of the O chromosome in European populations of Drosophila subobscura.

Molecular Evolution of Drosophila Germline Stem Cell and Neural Stem Cell Regulating Genes.

Here, we study the molecular evolution of a near complete set of genes that had functional evidence in the regulation of the Drosophila germline and neural stem cell. Some of these genes have previously been shown to be rapidly evolving by positive selection raising the possibility that stem cell genes as a group have elevated signatures of positive selection. Using recent Drosophila comparative genome sequences and population genomic sequences of Drosophila melanogaster, we have investigated both long- and short-term evolution occurring across these two different stem cell systems, and compared them with a carefully chosen random set of genes to represent the background rate of evolution.

The Drosophila bag of marbles Gene Interacts Genetically with Wolbachia and Shows Female-Specific Effects of Divergence.

Many reproductive proteins from diverse taxa evolve rapidly and adaptively. These proteins are typically involved in late stages of reproduction such as sperm development and fertilization, and are more often functional in males than females. Surprisingly, many germline stem cell (GSC) regulatory genes, which are essential for the earliest stages of reproduction, also evolve adaptively in Drosophila.

Population Genomics of Infectious and Integrated Wolbachia pipientis Genomes in Drosophila ananassae.

Coevolution between Drosophila and its endosymbiont Wolbachia pipientis has many intriguing aspects. For example, Drosophila ananassae hosts two forms of W. pipientis genomes: One being the infectious bacterial genome and the other integrated into the host nuclear genome.

A Genetic Incompatibility Accelerates Adaptation in Yeast.

During mismatch repair (MMR) MSH proteins bind to mismatches that form as the result of DNA replication errors and recruit MLH factors such as Mlh1-Pms1 to initiate excision and repair steps. Previously, we identified a negative epistatic interaction involving naturally occurring polymorphisms in the MLH1 and PMS1 genes of baker's yeast. Here we hypothesize that a mutagenic state resulting from this negative epistatic interaction increases the likelihood of obtaining beneficial mutations that can promote adaptation to stress conditions.

Correction: A nutrient-driven tRNA modification alters translational fidelity and genome-wide protein coding across an animal genus.

[This corrects the article DOI: 10.1371/journal.pbio.

Adaptive evolution of genes involved in the regulation of germline stem cells in Drosophila melanogaster and D. simulans.

Population genetic and comparative analyses in diverse taxa have shown that numerous genes involved in reproduction are adaptively evolving. Two genes involved in germline stem cell regulation, bag of marbles (bam) and benign gonial cell neoplasm (bgcn), have been shown previously to experience recurrent, adaptive evolution in both Drosophila melanogaster and D. simulans.

A nutrient-driven tRNA modification alters translational fidelity and genome-wide protein coding across an animal genus.

Natural selection favors efficient expression of encoded proteins, but the causes, mechanisms, and fitness consequences of evolved coding changes remain an area of aggressive inquiry. We report a large-scale reversal in the relative translational accuracy of codons across 12 fly species in the Drosophila/Sophophora genus. Because the reversal involves pairs of codons that are read by the same genomically encoded tRNAs, we hypothesize, and show by direct measurement, that a tRNA anticodon modification from guanosine to queuosine has coevolved with these genomic changes.

The coevolutionary period of Wolbachia pipientis infecting Drosophila ananassae and its impact on the evolution of the host germline stem cell regulating genes.

The endosymbiotic bacteria Wolbachia pipientis is known to infect a wide range of arthropod species yet less is known about the coevolutionary history it has with its hosts. Evidence of highly identical W. pipientis strains in evolutionary divergent hosts suggests horizontal transfer between hosts.