Beyond Haldane's rule: Sex-biased hybrid dysfunction for all modes of sex determination.

Haldane's rule occupies a special place in biology as one of the few 'rules' of speciation, with empirical support from hundreds of species. And yet, its classic purview is restricted taxonomically to the subset of organisms with heteromorphic sex chromosomes. I propose explicit acknowledgement of generalized hypotheses about Haldane's rule that frame sex bias in hybrid dysfunction broadly and irrespective of the sexual system.

Experimental evolution of hybrid populations to identify Dobzhansky-Muller incompatibility loci.

Epistatic interactions between loci that reduce fitness in interspecies hybrids, Dobzhansky-Muller incompatibilities (DMIs), contribute genetically to the inviability and infertility within hybrid populations. It remains a challenge, however, to identify the loci that contribute to DMIs as causes of reproductive isolation between species. Here, we assess through forward simulation the power of evolve-and-resequence (E&R) experimental evolution of hybrid populations to map DMI loci.

Sexual conflict, heterochrony and tissue specificity as evolutionary problems of adaptive plasticity in development.

Differential gene expression represents a fundamental cause and manifestation of phenotypic plasticity. Adaptive phenotypic plasticity in gene expression as a trait evolves when alleles that mediate gene regulation serve to increase organismal fitness by improving the alignment of variation in gene expression with variation in circumstances. Among the diverse circumstances that a gene encounters are distinct cell types, developmental stages and sexes, as well as an organism's extrinsic ecological environments.

Genomic diversity landscapes in outcrossing and selfing Caenorhabditis nematodes.

Caenorhabditis nematodes form an excellent model for studying how the mode of reproduction affects genetic diversity, as some species reproduce via outcrossing whereas others can self-fertilize. Currently, chromosome-level patterns of diversity and recombination are only available for self-reproducing Caenorhabditis, making the generality of genomic patterns across the genus unclear given the profound potential influence of reproductive mode. Here we present a whole-genome diversity landscape, coupled with a new genetic map, for the outcrossing nematode C.

Speciation and development.

Understanding general principles about the origin of species remains one of the foundational challenges in evolutionary biology. The genomic divergence between groups of individuals can spawn hybrid inviability and hybrid sterility, which presents a tantalizing developmental problem. Divergent developmental programs may yield either conserved or divergent phenotypes relative to ancestral traits, both of which can be responsible for reproductive isolation during the speciation process.

Guerrilla eugenics: gene drives in heritable human genome editing.

CRISPR-Cas9 genome editing can and has altered human genomes, bringing bioethical debates about this capability to the forefront of philosophical and policy considerations. Here, I consider the underexplored implications of CRISPR-Cas9 gene drives for heritable human genome editing. Modification gene drives applied to heritable human genome editing would introduce a novel form of involuntary eugenic practice that I term guerrilla eugenics.

Regulatory Divergence as a Mechanism for X-Autosome Incompatibilities in Caenorhabditis Nematodes.

The world's astounding biodiversity results from speciation, the process of formation of distinct species. Hybrids between species often have reduced fitness due to negative epistatic interactions between divergent genetic factors, as each lineage accumulated substitutions independently in their evolutionary history. Such negative genetic interactions can manifest as gene misexpression due to divergence in gene regulatory controls from mutations in cis-regulatory elements and trans-acting factors.

Synthetic gene drives as an anthropogenic evolutionary force.

Genetic drive represents a fundamental evolutionary force that can exact profound change to the genetic composition of populations by biasing allele transmission. Herein I propose that the use of synthetic homing gene drives, the human-mediated analog of endogenous genetic drives, warrants the designation of 'genetic welding' as an anthropogenic evolutionary force. Conceptually, this distinction parallels that of artificial and natural selection.

Salmonella-liberated dietary L-arabinose promotes expansion in superspreaders.

The molecular understanding of host-pathogen interactions in the gastrointestinal (GI) tract of superspreader hosts is incomplete. In a mouse model of chronic, asymptomatic Salmonella enterica serovar Typhimurium (S. Tm) infection, we performed untargeted metabolomics on the feces of mice and found that superspreader hosts possess distinct metabolic signatures compared with non-superspreaders, including differential levels of L-arabinose.

Bone Marrow Mesenchymal Stem Cells Induce Metabolic Plasticity in Estrogen Receptor-Positive Breast Cancer.

Unlabelled: Cancer cells reprogram energy metabolism through metabolic plasticity, adapting ATP-generating pathways in response to treatment or microenvironmental changes. Such adaptations enable cancer cells to resist standard therapy. We employed a coculture model of estrogen receptor-positive (ER+) breast cancer and mesenchymal stem cells (MSC) to model interactions of cancer cells with stromal microenvironments.

Temperature-dependent Small RNA Expression Depends on Wild Genetic Backgrounds of Caenorhabditis briggsae.

Geographically distinct populations can adapt to the temperature conditions of their local environment, leading to temperature-dependent fitness differences between populations. Consistent with local adaptation, phylogeographically distinct Caenorhabditis briggsae nematodes show distinct fitness responses to temperature. The genetic mechanisms underlying local adaptation, however, remain unresolved.

Effects of iron modulation on mesenchymal stem cell-induced drug resistance in estrogen receptor-positive breast cancer.

Patients with estrogen receptor-positive (ER+) breast cancer, the most common subtype, remain at risk for lethal metastatic disease years after diagnosis. Recurrence arises partly because tumor cells in bone marrow become resistant to estrogen-targeted therapy. Here, we utilized a co-culture model of bone marrow mesenchymal stem cells (MSCs) and ER+ breast cancer cells to recapitulate interactions of cancer cells in bone marrow niches.

The distribution of mutational effects on fitness in Caenorhabditis elegans inferred from standing genetic variation.

The distribution of fitness effects (DFE) for new mutations is one of the most theoretically important but difficult to estimate properties in population genetics. A crucial challenge to inferring the DFE from natural genetic variation is the sensitivity of the site frequency spectrum to factors like population size change, population substructure, genome structure, and nonrandom mating. Although inference methods aim to control for population size changes, the influence of nonrandom mating remains incompletely understood, despite being a common feature of many species.

Widespread misregulation of inter-species hybrid transcriptomes due to sex-specific and sex-chromosome regulatory evolution.

When gene regulatory networks diverge between species, their dysfunctional expression in inter-species hybrid individuals can create genetic incompatibilities that generate the developmental defects responsible for intrinsic post-zygotic reproductive isolation. Both cis- and trans-acting regulatory divergence can be hastened by directional selection through adaptation, sexual selection, and inter-sexual conflict, in addition to cryptic evolution under stabilizing selection. Dysfunctional sex-biased gene expression, in particular, may provide an important source of sexually-dimorphic genetic incompatibilities.

Speciation and the developmental alarm clock.

New species arise as the genomes of populations diverge. The developmental 'alarm clock' of speciation sounds off when sufficient divergence in genetic control of development leads hybrid individuals to infertility or inviability, the world awoken to the dawn of new species with intrinsic post-zygotic reproductive isolation. Some developmental stages will be more prone to hybrid dysfunction due to how molecular evolution interacts with the ontogenetic timing of gene expression.

Targeting disseminated estrogen-receptor-positive breast cancer cells in bone marrow.

Estrogen receptor-positive (ER+) breast cancer can recur up to 20 years after initial diagnosis. Delayed recurrences arise from disseminated tumors cells (DTCs) in sites such as bone marrow that remain quiescent during endocrine therapy and subsequently proliferate to produce clinically detectable metastases. Identifying therapies that eliminate DTCs and/or effectively target cells transitioning to proliferation promises to reduce risk of recurrence.

Enhanced mitochondrial fission suppresses signaling and metastasis in triple-negative breast cancer.

Background: Mitochondrial dynamics underlies malignant transformation, cancer progression, and response to treatment. Current research presents conflicting evidence for functions of mitochondrial fission and fusion in tumor progression. Here, we investigated how mitochondrial fission and fusion states regulate underlying processes of cancer progression and metastasis in triple-negative breast cancer (TNBC).

Males, Outcrossing, and Sexual Selection in Nematodes.

Males of provide a crucial practical tool in the laboratory, but, as the rarer and more finicky sex, have not enjoyed the same depth of research attention as hermaphrodites. Males, however, have attracted the attention of evolutionary biologists who are exploiting the system to test longstanding hypotheses about sexual selection, sexual conflict, transitions in reproductive mode, and genome evolution, as well as to make new discoveries about organismal biology. Here, we review the evolutionary concepts and data informed by study of males of and other We give special attention to the important role of sperm cells as a mediator of inter-male competition and male-female conflict that has led to drastic trait divergence across species, despite exceptional phenotypic conservation in many other morphological features.

Molecular evolution across developmental time reveals rapid divergence in early embryogenesis.

Ontogenetic development hinges on the changes in gene expression in time and space within an organism, suggesting that the demands of ontogenetic growth can impose or reveal predictable pattern in the molecular evolution of genes expressed dynamically across development. Here, we characterize coexpression modules of the transcriptome, using a time series of 30 points from early embryo to adult. By capturing the functional form of expression profiles with quantitative metrics, we find fastest evolution in the distinctive set of genes with transcript abundance that declines through development from a peak in young embryos.

Reproductive transitions in plants and animals: selfing syndrome, sexual selection and speciation.

The evolution of predominant self-fertilisation frequently coincides with the evolution of a collection of phenotypes that comprise the 'selfing syndrome', in both plants and animals. Genomic features also display a selfing syndrome. Selfing syndrome traits often involve changes to male and female reproductive characters that were subject to sexual selection and sexual conflict in the obligatorily outcrossing ancestor, including the gametic phase for both plants and animals.

Genome structure predicts modular transcriptome responses to genetic and environmental conditions.

Understanding the plasticity, robustness and modularity of transcriptome expression to genetic and environmental conditions is crucial to deciphering how organisms adapt in nature. To test how genome architecture influences transcriptome profiles, we quantified expression responses for distinct temperature-adapted genotypes of the nematode Caenorhabditis briggsae when exposed to chronic temperature stresses throughout development. We found that 56% of the 8,795 differentially expressed genes show genotype-specific changes in expression in response to temperature (genotype-by-environment interactions, GxE).

Neuro-genetic plasticity of Caenorhabditis elegans behavioral thermal tolerance.

Background: Animal responses to thermal stimuli involve intricate contributions of genetics, neurobiology and physiology, with temperature variation providing a pervasive environmental factor for natural selection. Thermal behavior thus exemplifies a dynamic trait that requires non-trivial phenotypic summaries to appropriately capture the trait in response to a changing environment. To characterize the deterministic and plastic components of thermal responses, we developed a novel micro-droplet assay of nematode behavior that permits information-dense summaries of dynamic behavioral phenotypes as reaction norms in response to increasing temperature (thermal tolerance curves, TTC).

Genetically Distinct Behavioral Modules Underlie Natural Variation in Thermal Performance Curves.

Thermal reaction norms pervade organismal traits as stereotyped responses to temperature, a fundamental environmental input into sensory and physiological systems. Locomotory behavior represents an especially plastic read-out of animal response, with its dynamic dependence on environmental stimuli presenting a challenge for analysis and for understanding the genomic architecture of heritable variation. Here we characterize behavioral reaction norms as thermal performance curves for the nematode , using a collection of 23 wild isolate genotypes and 153 recombinant inbred lines to quantify the extent of genetic and plastic variation in locomotory behavior to temperature changes.