Publications

ABSTRACT The vast diversity in nucleotide composition and architecture among bacterial genomes may be partly explained by inherent biases in the rates and spectra of spontaneous mutations. Bacterial genomes with multiple chromosomes are relatively unusual but some are relevant to human health, none more so than the causative agent of cholera, Vibrio cholerae . Here, we present the genome-wide mutation spectra in wild-type and mismatch repair (MMR) defective backgrounds of two Vibrio species, the low-GC% squid symbiont V. fischeri and the pathogen V. cholerae , collected under conditions that greatly minimize the efficiency of natural selection. In apparent contrast to their high diversity in nature, both wild-type V. fischeri and V. cholerae have among the lowest rates for base-substitution mutations (bpsms) and insertion-deletion mutations (indels) that have been measured, below 10 −3 /genome/generation. V. fischeri and V. cholerae have distinct mutation spectra, but both are AT-biased and produce a surprising number of multi-nucleotide indels. Furthermore, the loss of a functional MMR system caused the mutation spectra of these species to converge, implying that the MMR system itself contributes to species-specific mutation patterns. Bpsm and indel rates varied among genome regions, but do not explain the more rapid evolutionary rates of genes on chromosome 2, which likely result from weaker purifying selection. More generally, the very low mutation rates of Vibrio species correlate inversely with their immense population sizes and suggest that selection may not only have maximized replication fidelity but also optimized other polygenic traits relative to the constraints of genetic drift.

Abstract Mutation and recombination are the primary sources of genetic variation. To better understand the evolution of genetic variation, it is crucial to comprehensively investigate the processes involving mutation accumulation and recombination. In this study, we performed mutation accumulation experiments on four heterozygous diploid yeast species in the Saccharomycodaceae family to determine spontaneous mutation rates, mutation spectra, and losses of heterozygosity (LOH). We observed substantial variation in mutation rates and mutation spectra. We also observed high LOH rates (1.65–11.07×10−6 events per heterozygous site per cell division). Biases in spontaneous mutation and LOH together with selection ultimately shape the variable genome-wide nucleotide landscape in yeast species.

Significance Accurate transcription is required for the faithful expression of genetic information. If the fidelity of transcription is compromised, protein homeostasis, cell fate, and various metabolic processes are disrupted. Here, we demonstrate that mutagens can lower the fidelity of transcription in yeast, worms, flies, and mice by promoting the misincorporation of nucleotides by RNA polymerases. These observations establish a mechanism by which the environment, our lifestyle choices, and work-related exposures may promote the age of onset, severity, and progression of various diseases.

Abstract Comparing genomes of closely related genotypes from populations with distinct demographic histories can help reveal the impact of effective population size on genome evolution. For this purpose, we present a high quality genome assembly of Daphnia pulex (PA42), and compare this with the first sequenced genome of this species (TCO), which was derived from an isolate from a population with >90% reduction in nucleotide diversity. PA42 has numerous similarities to TCO at the gene level, with an average amino acid sequence identity of 98.8 and >60% of orthologous proteins identical. Nonetheless, there is a highly elevated number of genes in the TCO genome annotation, with ∼7000 excess genes appearing to be false positives. This view is supported by the high GC content, lack of introns, and short length of these suspicious gene annotations. Consistent with the view that reduced effective population size can facilitate the accumulation of slightly deleterious genomic features, we observe more proliferation of transposable elements (TEs) and a higher frequency of gained introns in the TCO genome.

ABSTRACT Recent application of mutation accumulation techniques combined with whole-genome sequencing (MA/WGS) has greatly promoted studies of spontaneous mutation. However, such explorations have rarely been conducted on marine organisms, and it is unclear how marine habitats have influenced genome stability. This report resolves the mutation rate and spectrum of the coral reef pathogen Vibrio shilonii , which causes coral bleaching and endangers the biodiversity maintained by coral reefs. We found that its mutation rate and spectrum are highly similar to those of other studied bacteria from various habitats, despite the saline environment. The mutational properties of this marine bacterium are thus controlled by other general evolutionary forces such as natural selection and genetic drift. We also found that as pH drops, the mutation rate decreases and the mutation spectrum is biased in the direction of generating G/C nucleotides. This implies that evolutionary features of this organism and perhaps other marine microbes might be altered by the increasingly acidic ocean water caused by excess CO 2 emission. Nonetheless, further exploration is needed as the pH range tested in this study was rather narrow and many other possible mutation determinants, such as carbonate increase, are associated with ocean acidification. IMPORTANCE This study explored the pH dependence of a bacterial genome-wide mutation rate. We discovered that the genome-wide rates of appearance of most mutation types decrease linearly and that the mutation spectrum is biased in generating more G/C nucleotides with pH drop in the coral reef pathogen V. shilonii .

Abstract Large-scale TSS profiling produces a high-resolution, quantitative picture of transcription initiation and core promoter locations within a genome. However, application of TSS profiling to date has largely been restricted to a small set of prominent model systems. We sought to characterize the cis -regulatory landscape of the water flea Daphnia pulex, an emerging model arthropod that reproduces both asexually ( via parthenogenesis) and sexually ( via meiosis). We performed CAGE with RNA isolated from D. pulex within three developmental states: sexual females, asexual females, and males. Identified TSSs were utilized to generate a ‘Daphnia Promoter Atlas’-a catalog of active promoters across the surveyed states. We carried out de novo motif discovery using CAGE-defined TSSs and identified eight candidate core promoter motifs; this collection includes canonical promoter elements ( e.g . TATA, Initiator) in addition to others lacking obvious orthologs. A comparison of promoter activities found evidence for considerable state-specific differential gene expression between states. Our work represents the first global definition of transcription initiation and promoter architecture in crustaceans. The Daphnia Promoter Atlas presented here provides a valuable resource for comparative study of cis -regulatory regions in arthropods, as well as for investigations into the circuitries that underpin meiosis and parthenogenesis.

This genome-wide analysis of SSR variation in Daphnia pulex indicates that several aspects of SSR variation are motif dependent and suggests that a combination of unit length variation and end repeat biased base substitution contribute to the unique spectrum of SSR repeat loci.

Hybridization plays a potentially important role in the origin of obligate parthenogenesis (OP) in many organisms. However, it remains controversial whether hybridization directly triggers the transition from sexual reproduction to obligate asexuality or a hybrid genetic background enables asexual species to persist. Furthermore, we know little about the specific genetic elements from the divergent, yet still hybridizing lineages responsible for this transition and how these elements are further spread to create other OP lineages. In this study, we address these questions in Daphnia pulex, where cyclically parthenogenetic (CP) and OP lineages coexist. Ancestry estimates and whole-genome association mapping using 32 OP isolates suggest that a complex hybridization history between the parental species D. pulex and D. pulicaria is responsible for the introgression of a set of 647 D. pulicaria single nucleotide polymorphism alleles that show perfect association with OP. Crossing experiments using males of OP lineages and females of CP lineages strongly support a polygenic basis for OP. Single-sperm analyses show that although normal meiotic recombination occurs in the production of haploid sperm by males of OP lineages, a significant proportion of such sperm are polyploid, suggesting that the spread of asexual elements through these males (i.e., contagious asexuality) is much less efficient than previously envisioned. Although the current Daphnia genome annotation does not provide mechanistic insight into the nature of the asexuality-associated alleles, these alleles should be considered as candidates for future investigations on the genetic underpinnings of OP.

We present complete results for the hadronic vacuum polarization (HVP) contribution to the muon anomalous magnetic moment $a_μ$ in the short- and intermediate-distance window regions, which account for roughly 10% and 35% of the total HVP contribution to $a_μ$, respectively. In particular, we perform lattice-QCD calculations for the isospin-symmetric connected and disconnected contributions, as well as corrections due to strong isospin-breaking. For the short-distance window observables, we investigate the so-called log-enhancement effects as well as the significant oscillations associated with staggered quarks in this region. For the dominant, isospin-symmetric light-quark connected contribution, we obtain $a^{ll,\,{\mathrm{SD}}}_μ(\mathrm{conn.}) = 48.139(11)_{\mathrm{stat}}(91)_{\mathrm{syst}}[92]_{\mathrm{total}} \times 10^{-10}$ and $a^{ll,\,{\mathrm{W}}}_μ(\mathrm{conn.}) = 206.90(14)_{\mathrm{stat}}(61)_{\mathrm{syst}}[63]_{\mathrm{total}} \times 10^{-10}$. We use Bayesian model averaging to fully estimate the covariance matrix between the individual contributions. Our determinations of the complete window contributions are $a^{\mathrm{SD}}_μ = 69.05(1)_{\mathrm{stat}}(21)_{\mathrm{syst}}[21]_{\mathrm{total}} \times 10^{-10}$ and $a^{\mathrm{W}}_μ = 236.45(17)_{\mathrm{stat}}(83)_{\mathrm{syst}}[85]_{\mathrm{total}} \times 10^{-10}$. This work is part of our ongoing effort to compute all contributions to HVP with an overall uncertainty at the few permille level.