A Deep Learning Approach for Detecting Copy Number Variation in Next-Generation Sequencing Data

This work is licensed under a Creative Commons Attribution 4.0 International License.Copy number variants (CNV) are associated with phenotypic variation in several species. However, properly detecting changes in copy numbers of sequences remains a difficult problem, especially in lower quality or lower coverage next-generation sequencing data. Here, inspired by recent applications of machine learning in genomics, we describe a method to detect duplications and deletions in short-read sequencing data. In low coverage data, machine learning appears to be more powerful in the detection of CNVs than the gold-standard methods of coverage estimation alone, and of equal power in high coverage data. We also demonstrate how replicating training sets allows a more precise detection of CNVs, even identifying novel CNVs in two genomes previously surveyed thoroughly for CNVs using long read data

Positive Selection and Horizontal Gene Transfer in the Genome of a Male-Killing Wolbachia

Wolbachia are a genus of widespread bacterial endosymbionts in which some strains can hijack or manipulate arthropod host reproduction. Male killing is one such manipulation in which these maternally transmitted bacteria benefit surviving daughters in part by removing competition with the sons for scarce resources. Despite previous findings of interesting genome features of microbial sex ratio distorters, the population genomics of male-killers remain largely uncharacterized. Here, we uncover several unique features of the genome and population genomics of four Arizonan populations of a male-killing Wolbachia strain, wInn, that infects mushroom-feeding Drosophila innubila. We first compared the wInn genome with other closely related Wolbachia genomes of Drosophila hosts in terms of genome content and confirm that the wInn genome is largely similar in overall gene content to the wMel strain infecting D. melanogaster. However, it also contains many unique genes and repetitive genetic elements that indicate lateral gene transfers between wInn and non-Drosophila eukaryotes. We also find that, in line with literature precedent, genes in the Wolbachia prophage and Octomom regions are under positive selection. Of all the genes under positive selection, many also show evidence of recent horizontal transfer among Wolbachia symbiont genomes. These dynamics of selection and horizontal gene transfer across the genomes of several Wolbachia strains and diverse host species may be important underlying factors in Wolbachia’s success as a male-killer of divergent host species

Indirect reduced-order modelling:Using nonlinear manifolds to conserve kinetic energy

Nonlinear dynamic analysis of complex engineering structures modelled using commercial finite element (FE) software is computationally expensive. Indirect reduced-order modelling strategies alleviate this cost by constructing low-dimensional models using a static solution dataset from the FE model. The applicability of such methods is typically limited to structures in which (a) the main source of nonlinearity is the quasi-static coupling between transverse and in-plane modes (i.e. membrane stretching); and (b) the amount of in-plane displacement is limited. We show that the second requirement arises from the fact that, in existing methods, in-plane kinetic energy is assumed to be negligible. For structures such as thin plates and slender beams with fixed/pinned boundary conditions, this is often reasonable, but in structures with free boundary conditions (e.g. cantilever beams), this assumption is violated. Here, we exploit the concept of nonlinear manifolds to show how the in-plane kinetic energy can be accounted for in the reduced dynamics, without requiring any additional information from the FE model. This new insight enables indirect reduction methods to be applied to a far wider range of structures while maintaining accuracy to higher deflection amplitudes. The accuracy of the proposed method is validated using an FE model of a cantilever beam

Balancing Selection Drives the Maintenance of Genetic Variation in Drosophila Antimicrobial Peptides

This work is licensed under a Creative Commons Attribution 4.0 International License.Genes involved in immune defense against pathogens provide some of the most well-known examples of both directional and balancing selection. Antimicrobial peptides (AMPs) are innate immune effector genes, playing a key role in pathogen clearance in many species, including Drosophila. Conflicting lines of evidence have suggested that AMPs may be under directional, balancing, or purifying selection. Here, we use both a linear model and control-gene-based approach to show that balancing selection is an important force shaping AMP diversity in Drosophila. In Drosophila melanogaster, this is most clearly observed in ancestral African populations. Furthermore, the signature of balancing selection is even more striking once background selection has been accounted for. Balancing selection also acts on AMPs in Drosophila mauritiana, an isolated island endemic separated from D. melanogaster by about 4 Myr of evolution. This suggests that balancing selection may be broadly acting to maintain adaptive diversity in Drosophila AMPs, as has been found in other taxa

The Genome of Drosophila innubila Reveals Lineage-Specific Patterns of Selection in Immune Genes

This is a pre-copyedited, author-produced version of an article accepted for publication in Molecular Biology and Evolution following peer review. The version of record Hill, T., Koseva, B. S., & Unckless, R. L. (2019). The Genome of Drosophila innubila Reveals Lineage-Specific Patterns of Selection in Immune Genes. Molecular biology and evolution, 36(7), 1405–1417. https://doi.org/10.1093/molbev/msz059 is available online at: doi.org/10.1093/molbev/msz059. This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.Pathogenic microbes can exert extraordinary evolutionary pressure on their hosts. They can spread rapidly and sicken or even kill their host to promote their own proliferation. Because of this strong selective pressure, immune genes are some of the fastest evolving genes across metazoans, as highlighted in mammals and insects. Drosophila melanogaster serves as a powerful model for studying host/pathogen evolution. While Drosophila melanogaster are frequently exposed to various pathogens, little is known about D. melanogaster’s ecology, or if they are representative of other Drosophila species in terms of pathogen pressure. Here, we characterize the genome of Drosophila innubila, a mushroom-feeding species highly diverged from D. melanogaster and investigate the evolution of the immune system. We find substantial differences in the rates of evolution of immune pathways between D. innubila and D. melanogaster. Contrasting what was previously found for D. melanogaster, we find little evidence of rapid evolution of the antiviral RNAi genes and high rates of evolution in the Toll pathway. This suggests that, while immune genes tend to be rapidly evolving in most species, the specific genes that are fastest evolving may depend either on the pathogens faced by the host and/or divergence in the basic architecture of the host’s immune system.NIH Grant P20 GM103638P20 GM103418Max Kade foundation postdoctoral fellowshipNIH grant P20 GM103418NIH R00 GM114714NIH R01 AI13915

Rapid divergence of the male reproductive proteins in the Drosophila dunni group and implications for postmating incompatibilities between species

Proteins involved in post-copulatory interactions between males and females are among the fastest evolving genes in many species, usually attributed to their involvement in reproductive conflict. As a result, these proteins are thought to often be involved in the formation of postmating-prezygotic incompatibilities between species. The Drosophila dunni subgroup consists of a dozen recently diverged species found across the Caribbean islands with varying levels of hybrid incompatibility. We performed experimental crosses between species in the dunni group and see some evidence of hybrid incompatibilities. We also find evidence of reduced survival following hybrid mating, likely due to postmating-prezygotic incompatibilities. We assessed rates of evolution between these species genomes and find evidence of rapid evolution and divergence of some reproductive proteins, specifically the seminal fluid proteins. This work suggests the rapid evolution of seminal fluid proteins may be associated with postmating-prezygotic isolation, which acts as a barrier for gene flow between even the most closely related species