On the correspondence between the transcriptomic response of a compound and its effects on its targets.

Better understanding the transcriptomic response produced by a compound perturbing its targets can shed light on the underlying biological processes regulated by the compound. However, establishing the relationship between the induced transcriptomic response and the target of a compound is non-trivial, partly because targets are rarely differentially expressed. Therefore, connecting both modalities requires orthogonal information (e.g., pathway or functional information). Here, we present a comprehensive study aimed at exploring this relationship by leveraging thousands of transcriptomic experiments and target data for over 2000 compounds. Firstly, we confirm that compound-target information does not correlate as expected with the transcriptomic signatures induced by a compound. However, we reveal how the concordance between both modalities increases by connecting pathway and target information. Additionally, we investigate whether compounds that target the same proteins induce a similar transcriptomic response and conversely, whether compounds with similar transcriptomic responses share the same target proteins. While our findings suggest that this is generally not the case, we did observe that compounds with similar transcriptomic profiles are more likely to share at least one protein target and common therapeutic applications. Finally, we demonstrate how to exploit the relationship between both modalities for mechanism of action deconvolution by presenting a case scenario involving a few compound pairs with high similarity.

NLR diversity and candidate fusiform rust resistance genes in loblolly pine.

Resistance to fusiform rust disease in loblolly pine (Pinus taeda) is a classic gene-for-gene system. Early resistance gene mapping in the P. taeda family 10-5 identified RAPD markers for a major fusiform rust resistance gene, Fr1. More recently, single nucleotide polymorphism (SNP) markers associated with resistance were mapped to a full-length gene model in the loblolly pine genome encoding for a nucleotide-binding site leucine-rich repeat (NLR) protein. NLR genes are one of the most abundant gene families in plant genomes and are involved in effector-triggered immunity. Inter- and intraspecies studies of NLR gene diversity and expression have resulted in improved disease resistance. To characterize NLR gene diversity and discover potential resistance genes, we assembled de novo transcriptomes from 92 loblolly genotypes from across the natural range of the species. In these transcriptomes, we identified novel NLR transcripts that are not present in the loblolly pine reference genome and found significant geographic diversity of NLR genes providing evidence of gene family evolution. We designed capture probes for these NLRs to identify and map SNPs that stably cosegregate with resistance to the SC20-21 isolate of Cronartium quercuum f.sp. fusiforme (Cqf) in half-sib progeny of the 10-5 family. We identified 10 SNPs and 2 quantitative trait loci associated with resistance to SC20-21 Cqf. The geographic diversity of NLR genes provides evidence of NLR gene family evolution in loblolly pine. The SNPs associated with rust resistance provide a resource to enhance breeding and deployment of resistant pine seedlings.

Genome assembly of the roundjaw bonefish (Albula glossodonta), a vulnerable circumtropical sportfish.

The roundjaw bonefish, Albula glossodonta, is the most widespread albulid in the Indo-Pacific and is vulnerable to extinction. We assembled the genome of a roundjaw bonefish from Hawai'i, USA, which will be instrumental for effective transboundary management and conservation when paired with population genomics datasets. The 1.05 gigabase pair (Gbp) contig-level assembly had a 4.75 megabase pair (Mbp) NG50 and a maximum contig length of 28.2 Mbp. Scaffolding yielded an LG50 of 20 and an NG50 of 14.49 Mbp, with the longest scaffold reaching 42.29 Mbp. The genome comprised 6.5% repetitive elements and was annotated with 28.3 K protein-coding genes. We then evaluated population genetic connectivity between six atolls in the Western Indian Ocean with 38,355 SNP loci across 66 A. glossodonta individuals. We discerned shallow population structure and observed genetic homogeneity between atolls in Seychelles and reduced gene flow between Seychelles and Mauritius. The South Equatorial Current might be the limiting mechanism of this reduced gene flow. The genome assembly will be useful for addressing taxonomic uncertainties of bonefishes globally.

The genomic basis of evolutionary differentiation among honey bees.

In contrast to the western honey bee, Apis mellifera, other honey bee species have been largely neglected despite their importance and diversity. The genetic basis of the evolutionary diversification of honey bees remains largely unknown. Here, we provide a genome-wide comparison of three honey bee species, each representing one of the three subgenera of honey bees, namely the dwarf (Apis florea), giant (A. dorsata), and cavity-nesting (A. mellifera) honey bees with bumblebees as an outgroup. Our analyses resolve the phylogeny of honey bees with the dwarf honey bees diverging first. We find that evolution of increased eusocial complexity in Apis proceeds via increases in the complexity of gene regulation, which is in agreement with previous studies. However, this process seems to be related to pathways other than transcriptional control. Positive selection patterns across Apis reveal a trade-off between maintaining genome stability and generating genetic diversity, with a rapidly evolving piRNA pathway leading to genomes depleted of transposable elements, and a rapidly evolving DNA repair pathway associated with high recombination rates in all Apis species. Diversification within Apis is accompanied by positive selection in several genes whose putative functions present candidate mechanisms for lineage-specific adaptations, such as migration, immunity, and nesting behavior.

Social evolution. Genomic signatures of evolutionary transitions from solitary to group living.

The evolution of eusociality is one of the major transitions in evolution, but the underlying genomic changes are unknown. We compared the genomes of 10 bee species that vary in social complexity, representing multiple independent transitions in social evolution, and report three major findings. First, many important genes show evidence of neutral evolution as a consequence of relaxed selection with increasing social complexity. Second, there is no single road map to eusociality; independent evolutionary transitions in sociality have independent genetic underpinnings. Third, though clearly independent in detail, these transitions do have similar general features, including an increase in constrained protein evolution accompanied by increases in the potential for gene regulation and decreases in diversity and abundance of transposable elements. Eusociality may arise through different mechanisms each time, but would likely always involve an increase in the complexity of gene networks.

Transposable element islands facilitate adaptation to novel environments in an invasive species.

Adaptation requires genetic variation, but founder populations are generally genetically depleted. Here we sequence two populations of an inbred ant that diverge in phenotype to determine how variability is generated. Cardiocondyla obscurior has the smallest of the sequenced ant genomes and its structure suggests a fundamental role of transposable elements (TEs) in adaptive evolution. Accumulations of TEs (TE islands) comprising 7.18% of the genome evolve faster than other regions with regard to single-nucleotide variants, gene/exon duplications and deletions and gene homology. A non-random distribution of gene families, larvae/adult specific gene expression and signs of differential methylation in TE islands indicate intragenomic differences in regulation, evolutionary rates and coalescent effective population size. Our study reveals a tripartite interplay between TEs, life history and adaptation in an invasive species.

A beginner's guide to eukaryotic genome annotation.

The falling cost of genome sequencing is having a marked impact on the research community with respect to which genomes are sequenced and how and where they are annotated. Genome annotation projects have generally become small-scale affairs that are often carried out by an individual laboratory. Although annotating a eukaryotic genome assembly is now within the reach of non-experts, it remains a challenging task. Here we provide an overview of the genome annotation process and the available tools and describe some best-practice approaches.

SpedeSTEM: a rapid and accurate method for species delimitation.

We describe a software package (SpedeSTEM) that allows researchers to conduct a species delimitation analysis using intraspecific genetic data. Our method operates under the assumption that a priori information regarding group membership is available, for example that samples are drawn from some number of described subspecies, races or distinct morphotypes. SpedeSTEM proceeds by calculating the maximum likelihood species tree from all hierarchical arrangements of the sampled alleles and uses information theory to quantify the model probability of each permutation. SpedeSTEM is tested here against empirical and simulated data; results indicate that evolutionary lineages that diverged as few as 0.5N generations in the past can be validated as distinct using sequence data from little as five loci. This work enables speciation investigations to identify lineages that are evolutionarily distinct and thus have the potential to form new species before these lineages acquire secondary characteristics such as reproductive isolation or morphological differentiation that are commonly used to define species.