Identifying novel gene dysregulation associated with opioid overdose death: A meta-analysis of differential gene expression in human prefrontal cortex.

Only recently have human postmortem brain studies of differential gene expression (DGE) associated with opioid overdose death (OOD) been published; sample sizes from these studies have been modest (N = 40-153). To increase statistical power to identify OOD-associated genes, we leveraged human prefrontal cortex RNAseq data from four independent OOD studies and conducted a transcriptome-wide DGE meta-analysis (N = 285). Using a unified gene expression data processing and analysis framework across studies, we meta-analyzed 20 098 genes and found 335 significant differentially expressed genes (DEGs) by OOD status (false discovery rate < 0.05). Of these, 66 DEGs were among the list of 303 genes reported as OOD-associated in prior prefrontal cortex molecular studies, including genes/gene families (e.g., OPRK1, NPAS4, DUSP, EGR). The remaining 269 DEGs were not previously reported (e.g., NR4A2, SYT1, HCRTR2, BDNF). There was little evidence of genetic drivers for the observed differences in gene expression between opioid addiction cases and controls. Enrichment analyses for the DEGs across molecular pathway and biological process databases highlight an interconnected set of genes and pathways from orexin and tyrosine kinase receptors through MEK/ERK/MAPK signaling to affect neuronal plasticity.

Estimating phylogenies from genomes: A beginners review of commonly used genomic data in vertebrate phylogenomics.

Despite the increasing feasibility of sequencing whole genomes from diverse taxa, a persistent problem in phylogenomics is the selection of appropriate genetic markers or loci for a given taxonomic group or research question. In this review, we aim to streamline the decision-making process when selecting specific markers to use in phylogenomic studies by introducing commonly used types of genomic markers, their evolutionary characteristics, and their associated uses in phylogenomics. Specifically, we review the utilities of ultraconserved elements (including flanking regions), anchored hybrid enrichment loci, conserved nonexonic elements, untranslated regions, introns, exons, mitochondrial DNA, single nucleotide polymorphisms, and anonymous regions (nonspecific regions that are evenly or randomly distributed across the genome). These various genomic elements and regions differ in their substitution rates, likelihood of neutrality or of being strongly linked to loci under selection, and mode of inheritance, each of which are important considerations in phylogenomic reconstruction. These features may give each type of marker important advantages and disadvantages depending on the biological question, number of taxa sampled, evolutionary timescale, cost effectiveness, and analytical methods used. We provide a concise outline as a resource to efficiently consider key aspects of each type of genetic marker. There are many factors to consider when designing phylogenomic studies, and this review may serve as a primer when weighing options between multiple potential phylogenomic markers.

Belonging in STEM: an interactive, iterative approach to create and maintain a diverse learning community.

Diversity is a key driver of scientific innovation, yet fields in science, technology, engineering, and mathematics (STEM) have struggled to retain diverse communities. Research suggests that fostering a sense of belonging is critical for retaining diversity. We propose an iterative process that aims to improve sense of belonging among laboratory (lab) members through self-reflection and community collective action.

Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans.

Approximately three percent of the human genome is occupied by microsatellites: a type of short tandem repeat (STR). Microsatellites have well established effects on (a) the genetic structure of diverse human populations and (b) expression of nearby genes. These lines of inquiry have uncovered 3,984 ethnically biased microsatellite loci (EBML) and 28,375 expression STRs (eSTRs), respectively. We hypothesize that a combination of EBML, eSTRs, and gene expression data (RNA-seq) can be used to show that microsatellites contribute to differential gene expression and phenotype in human populations. In fact, our previous study demonstrated a degree of mutual overlap between EBML and eSTRs but fell short of quantifying effects on gene expression. The present work aims to narrow the gap. First, we identify 313 overlapping EBML/eSTRs and recapitulate their mutual overlap. The 313 EBML/eSTRs are then characterized across ethnicity and tissue type. We use RNA-seq data to pursue validation of 49 regions that affect whole blood gene expression; 32 out of 54 affected genes are differentially expressed in Africans and Europeans. We quantify the relative contribution of these 32 genes to differential expression; fold change tends to be less than other differentially expressed genes. Repeat length correlates with expression for 15 of the 32 genes; two are conspicuously involved in glutathione metabolism. Finally, we repurpose a mathematical model of glutathione metabolism to investigate how a single polymorphic microsatellite affects phenotype. We conclude with a testable prediction that microsatellite polymorphisms affect GPX7 expression and oxidative stress in Africans and Europeans.

Sex-linked genetic diversity and differentiation in a globally distributed avian species complex.

Sex chromosomes often bear distinct patterns of genetic variation due to unique patterns of inheritance and demography. The processes of mutation, recombination, genetic drift and selection also influence rates of evolution on sex chromosomes differently than autosomes. Measuring such differences provides information about how these processes shape genomic variation and their roles in the origin of species. To test hypotheses and predictions about patterns of autosomal and sex-linked genomic diversity and differentiation, we measured population genetic statistics within and between populations and subspecies of the barn swallow (Hirundo rustica) and performed explicit comparisons between autosomal and Z-linked genomic regions. We first tested for evidence of low Z-linked genetic diversity and high Z-linked population differentiation relative to autosomes, then for evidence that the Z chromosome bears greater ancestry information due to faster lineage sorting. Finally, we investigated geographical clines across hybrid zones for evidence that the Z chromosome is resistant to introgression due to selection against hybrids. We found evidence that the barn swallow mating system, demographic history and linked selection each contribute to low Z-linked diversity and high Z-linked differentiation. While incomplete lineage sorting is rampant across the genome, our results indicate faster sorting of ancestral polymorphism on the Z. Finally, hybrid zone analyses indicate barriers to introgression on the Z chromosome, suggesting that sex-linked traits are important in reproductive isolation, especially in migratory divide regions. Our study highlights how selection, gene flow and demography shape sex-linked genetic diversity and underlines the relevance of the Z chromosome in speciation.

Complete mitochondrial genomes provide current refined phylogenomic hypotheses for relationships among ten Hirundo species.

Hirundo is the most species-rich genus of the passerine swallow family (Hirundinidae) and has a cosmopolitan distribution. Here we report the complete, annotated mitochondrial genomes for 25 individuals from 10 of the 14 extant Hirundo species; these include representatives from four subspecies of the barn swallow, H. rustica. Mitogenomes were conserved in size, ranging from 18,500 to 18,700 base pairs. They all contained 13 protein-coding regions, 22 tRNAs, a control region, and large and small ribosomal subunits. Phylogenetic analysis resolved most of the relationships between the studied species and subspecies which were largely consistent with previously published trees. Several new relationships were observed within the phylogeny that could have only been discovered with the increased amount of genetic material. This study represents the largest Hirundo mitochondrial phylogeny to date, and could serve as a vital tool for other studies focusing on the evolution of the Hirundo genus.