Complete mitochondrial genome of the Starhead Topminnow Fundulus dispar (Cyprinodontiformes: Fundulidae).

Topminnows of the Teleost genus Fundulus serve as model organisms in ecotoxicology because of their broad physiological tolerance and propensity to breed in captivity. This research has been primarily limited to intraspecific comparisons, due to incomplete understanding of the evolutionary history of the genus, which is necessary for use of phylogenetic comparative methods. Interspecific relationships of topminnows remain unresolved, despite recent advances in mitochondrial and nuclear genome sequencing. Specifically, interrelationships of a group containing the starhead topminnows (Fundulus blairae, F. dispar, F. escambiae, F. lineolatus, and F. nottii) typically yield low node support values. Here, we present the first annotated mitochondrial genome of the Starhead Topminnow (F. dispar) and provide a phylogenetic hypothesis for starhead topminnows within the genus Fundulus. DNA was isolated from a specimen of F. dispar collected in Kentucky, USA. The circular genome is 16,564 bp long and contains 13 protein-coding genes, two ribosomal RNAs (rRNA), 22 transfer RNAs (tRNA), and one control region (D-loop). Our phylogenetic analysis supports a sister relationship between F. dispar and a group containing F. notatus and F. olivaceus. This data helps to resolve the phylogenetic placement of starhead topminnows.

Mitochondrial haplotype modulates genome expression and mitochondrial structure/function in cardiomyocytes following volume overload.

Mitochondrial DNA (mtDNA) haplotype regulates mitochondrial structure/function and reactive oxygen species in aortocaval fistula (ACF) in mice. Here, we unravel the mitochondrial haplotype effects on cardiomyocyte mitochondrial ultrastructure and transcriptome response to ACF in vivo. Phenotypic responses and quantitative transmission electron microscopy (TEM) and RNA sequence at 3 days were determined after sham surgery or ACF in vivo in cardiomyocytes from wild-type (WT) C57BL/6J (C57n:C57mt) and C3H/HeN (C3Hn:C3Hmt) and mitochondrial nuclear exchange mice (C57n:C3Hmt or C3Hn:C57mt). Quantitative TEM of cardiomyocyte mitochondria C3HWT hearts have more electron-dense compact mitochondrial cristae compared with C57WT. In response to ACF, mitochondrial area and cristae integrity are normal in C3HWT; however, there is mitochondrial swelling, cristae lysis, and disorganization in both C57WT and MNX hearts. Tissue analysis shows that C3HWT hearts have increased autophagy, antioxidant, and glucose fatty acid oxidation-related genes compared with C57WT. Comparative transcriptomic analysis of cardiomyocytes from ACF was dependent upon mtDNA haplotype. C57mtDNA haplotype was associated with increased inflammatory/protein synthesis pathways and downregulation of bioenergetic pathways, whereas C3HmtDNA showed upregulation of autophagy genes. In conclusion, ACF in vivo shows a protective response of C3Hmt haplotype that is in large part driven by mitochondrial nuclear genome interaction.NEW & NOTEWORTHY The results of this study support the effects of mtDNA haplotype on nuclear gene expression in cardiomyocytes. Currently, there is no acceptable therapy for volume overload due to mitral regurgitation. The findings of this study could suggest that mtDNA haplotype activates different pathways after ACF warrants further investigations on human population of heart disease from different ancestry backgrounds.

Complete mitochondrial genome of a livebearing freshwater fish (Cyprinodontiformes: Poeciliidae): Poecilia parae.

Members of the fish family Poeciliidae (livebearing 'tooth-carps') have historically been used as models in medical research, behavior ecology, and biological control. This group of primarily freshwater fishes is highly tolerant to environmental factors such as salinity and warm temperatures and includes some invasive species. Here, we present the mitochondrial genome of Poecilia parae. A representative of this species was obtained from Suriname. The complete mitochondrial genome was sequenced using Oxford Nanopore technology and is 16,559 bp long. The genome contains 13 protein-coding genes, two ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), and one control region (D-loop). Phylogenetic analysis yielded topologies similar to those previously published. The data generated here will be useful in future studies of comparative biology and those utilizing environmental DNA (eDNA).

Speciation genomics and the role of depth in the divergence of rockfishes (Sebastes) revealed through Pool-seq analysis of enriched sequences.

Speciation in the marine environment is challenged by the wide geographic distribution of many taxa and potential for high rates of gene flow through larval dispersal mechanisms. Depth has recently been proposed as a potential driver of ecological divergence in fishes, and yet it is unclear how adaptation along these gradients' shapes genomic divergence. The genus Sebastes contains numerous species pairs that are depth-segregated and can provide a better understanding of the mode and tempo of genomic diversification. Here, we present exome data on two species pairs of rockfishes that are depth-segregated and have different degrees of divergence: S. chlorostictus-S. rosenblatti and S. crocotulus-S. miniatus. We were able to reliably identify "islands of divergence" in the species pair with more recent divergence (S. chlorostictus-S. rosenblatti) and discovered a number of genes associated with neurosensory function, suggesting a role for this pathway in the early speciation process. We also reconstructed demographic histories of divergence and found the best supported model was isolation followed by asymmetric secondary contact for both species pairs. These results suggest past ecological/geographic isolation followed by asymmetric secondary contact of deep to shallow species. Our results provide another example of using rockfish as a model for studying speciation and support the role of depth as an important mechanism for diversification in the marine environment.

The complete mitochondrial genome of the Tennessee Dace (Chrosomus tennesseensis).

The Tennessee Dace, Chrosomus tennesseensis (Starnes and Jenkins 1988), is a small minnow (Cypriniformes: Leuciscidae) found in the upper Tennessee River watershed and Graves Creek, in the Mobile River watershed. Chrosomus tennesseensis occurs sporadically throughout its range and has been listed as vulnerable by the IUCN (NatureServe). Until recently, C. tennesseensis had been known only to occur in the upper Tennessee River watershed, however, it has been discovered in headwaters of the Black Warrior River of the Mobile River watershed. We sequenced the mitochondrial genome of C. tennesseensis collected in the Mobile River watershed to better understand the colonization of the Mobile River watershed and the interspecific relationships of Chrosomus. Furthermore, the availability of the mitochondrial genome will assist in designing specific environmental DNA (eDNA) primers that will allow for less intrusive sampling of threatened and endangered Chrosomus species.

Diversification along a benthic to pelagic gradient contributes to fish diversity in the world's largest lake (Lake Baikal, Russia).

Insights into the generation of diversity in both plants and animals have relied heavily on studying speciation in adaptive radiations. Russia's Lake Baikal has facilitated a putative adaptive radiation of cottid fishes (sculpins), some of which are highly specialized to inhabit novel niches created by the lake's unique geology and ecology. Here, we test evolutionary relationships and novel morphological adaptation in a piece of this radiation: the Baikal cottid genus, Cottocomephorus, a morphologically derived benthopelagic genus of three described species. We used a combination of mitochondrial DNA and restriction site associated DNA sequencing from all Cottocomephorus species. Analysis of mitochondrial cytochrome b haplotypes was only able to two resolve two lineages: C. grewingkii and C. comephoroides/inermis. Phylogenetic inference, principal component analysis, and faststructure of genome-wide SNPs uncovered three lineages within Cottocomephorus: C. comephoroides, C. inermis and C. grewingkii. We found recent divergence and admixture between C. comephoroides and C. inermis and deep divergence between these two species and C. grewingkii. Contrasting other fish radiations, we found no evidence of ancient hybridization among Cottocomephorus species. Digital morphology revealed highly derived pelagic phenotypes that reflect divergence by specialization to the benthopelagic niche in Cottocomephorus. Among Cottocomephorus species, we found evidence of ongoing adaptation to the pelagic zone. This pattern highlights the importance of speciation along a benthic-pelagic gradient seen in Cottocomephorus and across other adaptive fish radiations.

A need for null models in understanding disease transmission: the example of Mycobacterium ulcerans (Buruli ulcer disease).

Understanding the interactions of ecosystems, humans and pathogens is important for disease risk estimation. This is particularly true for neglected and newly emerging diseases where modes and efficiencies of transmission leading to epidemics are not well understood. Using a model for other emerging diseases, the neglected tropical skin disease Buruli ulcer (BU), we systematically review the literature on transmission of the etiologic agent, Mycobacterium ulcerans (MU), within a One Health/EcoHealth framework and against Hill's nine criteria and Koch's postulates for making strong inference in disease systems. Using this strong inference approach, we advocate a null hypothesis for MU transmission and other understudied disease systems. The null should be tested against alternative vector or host roles in pathogen transmission to better inform disease management. We propose a re-evaluation of what is necessary to identify and confirm hosts, reservoirs and vectors associated with environmental pathogen replication, dispersal and transmission; critically review alternative environmental sources of MU that may be important for transmission, including invertebrate and vertebrate species, plants and biofilms on aquatic substrates; and conclude with placing BU within the context of other neglected and emerging infectious diseases with intricate ecological relationships that lead to disease in humans, wildlife and domestic animals.

Randomization, design and analysis for interdependency in aging research: no person or mouse is an island.

Investigators traditionally use randomized designs and corresponding analysis procedures to make causal inferences about the effects of interventions, assuming independence between an individual's outcome and treatment assignment and the outcomes of other individuals in the study. Often, such independence may not hold. We provide examples of interdependency in model organism studies and human trials and group effects in aging research and then discuss methodologic issues and solutions. We group methodologic issues as they pertain to (1) single-stage individually randomized trials; (2) cluster-randomized controlled trials; (3) pseudo-cluster-randomized trials; (4) individually randomized group treatment; and (5) two-stage randomized designs. Although we present possible strategies for design and analysis to improve the rigor, accuracy and reproducibility of the science, we also acknowledge real-world constraints. Consequences of nonadherence, differential attrition or missing data, unintended exposure to multiple treatments and other practical realities can be reduced with careful planning, proper study designs and best practices.

Origins and evolution of extreme life span in Pacific Ocean rockfishes.

Pacific Ocean rockfishes (genus Sebastes) exhibit extreme variation in life span, with some species being among the most long-lived extant vertebrates. We de novo assembled the genomes of 88 rockfish species and from these identified repeated signatures of positive selection in DNA repair pathways in long-lived taxa and 137 longevity-associated genes with direct effects on life span through insulin signaling and with pleiotropic effects through size and environmental adaptations. A genome-wide screen of structural variation reveals copy number expansions in the immune modulatory butyrophilin gene family in long-lived species. The evolution of different rockfish life histories is coupled to genetic diversity and reshapes the mutational spectrum driving segregating CpG→TpG variants in long-lived species. These analyses highlight the genetic innovations that underlie life history trait adaptations and, in turn, how they shape genomic diversity.

The complete mitochondrial genome of the Variable Platyfish Xiphophorus variatus.

We present the complete mitochondrial genome sequence of the Variable Platyfish, Xiphophorus variatus (Meek 1904) (Cyprinodontiformes: Poeciliidae). The genome consists of 16,624 bp which encodes 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs, and 1 control region. Genome-wide nucleotide composition is 27.79% adenine, 31.11% cytosine, 15.63% guanine, and 25.48% thymine. The X. variatus mitochondrial genome shares similar GC content and identical gene order and gene strand location with other members of Poeciliidae. The sequence presented herein will be of utility for future phylogenetic and biomedical research and for designing primers for species detection from environmental DNA samples.

Complete Genome Sequences of Mycobacteriophages OKaNui and DroogsArmy.

Mycobacteriophages OKaNui and DroogsArmy were isolated from soil using the bacterial host Mycobacterium smegmatis mc2155, which belongs to the phylum Actinobacteria OKaNui was discovered in east Mississippi and DroogsArmy in west Alabama in the United States. The genomes of OKaNui and DroogsArmy were 51,424 bp and 53,254 bp long, respectively.

Complete Genome Sequences of Mycobacteriophages Candle, Schatzie, Sumter, and Waleliano.

Mycobacteriophages Candle, Schatzie, Sumter, and Waleliano were isolated from soil using the host bacterium Mycobacterium smegmatis mc2155. Candle, Schatzie, and Sumter were discovered in Alabama and Waleliano in Maryland. The bacteriophages have been assigned clusters based on nucleotide similarity, as follows: Candle, R; Schatzie, J; Sumter, A1; and Waleliano, B4.

Complete Genome Sequences of Mycobacteriophages Kwksand96 and Cane17.

Bacteriophages Kwksand96 and Cane17 were isolated from Mycobacterium smegmatis mc2155. M. smegmatis is host to the highest number of phages analyzed from one species. Both mycobacteriophages were isolated from soil in west Alabama. Kwksand96 and Cane17 belong to subclusters B1 and C1, respectively, based on mycobacteriophage nucleotide sequence similarity.

Mitochondrial - nuclear genetic interaction modulates whole body metabolism, adiposity and gene expression in vivo.

We hypothesized that changes in the mitochondrial DNA (mtDNA) would significantly influence whole body metabolism, adiposity and gene expression in response to diet. Because it is not feasible to directly test these predictions in humans we used Mitochondrial-Nuclear eXchange mice, which have reciprocally exchanged nuclear and mitochondrial genomes between different Mus musculus strains. Results demonstrate that nuclear-mitochondrial genetic background combination significantly alters metabolic efficiency and body composition. Comparative RNA sequencing analysis in adipose tissues also showed a clear influence of the mtDNA on regulating nuclear gene expression on the same nuclear background (up to a 10-fold change in the number of differentially expressed genes), revealing that neither Mendelian nor mitochondrial genetics unilaterally control gene expression. Additional analyses indicate that nuclear-mitochondrial genome combination modulates gene expression in a manner heretofore not described. These findings provide a new framework for understanding complex genetic disease susceptibility.

Genome Sequence of a Newly Isolated F2 Subcluster Mycobacteriophage from the Black Belt Geological Region of Western Alabama.

The bacteriophage Demsculpinboyz was discovered in a soil sample from the Black Belt region of Alabama using Mycobacterium smegmatis mc2155 as its host. The genome is 57,437 bp long and contains 116 protein-coding genes. It belongs to the F2 subcluster, which has only five other members.

Migration of mitochondrial DNA in the nuclear genome of colorectal adenocarcinoma.

BACKGROUND: Colorectal adenocarcinomas are characterized by abnormal mitochondrial DNA (mtDNA) copy number and genomic instability, but a molecular interaction between mitochondrial and nuclear genome remains unknown. Here we report the discovery of increased copies of nuclear mtDNA (NUMT) in colorectal adenocarcinomas, which supports link between mtDNA and genomic instability in the nucleus. We name this phenomenon of nuclear occurrence of mitochondrial component as numtogenesis. We provide a description of NUMT abundance and distribution in tumor versus matched blood-derived normal genomes. METHODS: Whole-genome sequence data were obtained for colon adenocarcinoma and rectum adenocarcinoma patients participating in The Cancer Genome Atlas, via the Cancer Genomics Hub, using the GeneTorrent file acquisition tool. Data were analyzed to determine NUMT proportion and distribution on a genome-wide scale. A NUMT suppressor gene was identified by comparing numtogenesis in other organisms. RESULTS: Our study reveals that colorectal adenocarcinoma genomes, on average, contains up to 4.2-fold more somatic NUMTs than matched normal genomes. Women colorectal tumors contained more NUMT than men. NUMT abundance in tumor predicted parallel abundance in blood. NUMT abundance positively correlated with GC content and gene density. Increased numtogenesis was observed with higher mortality. We identified YME1L1, a human homolog of yeast YME1 (yeast mitochondrial DNA escape 1) to be frequently mutated in colorectal tumors. YME1L1 was also mutated in tumors derived from other tissues. We show that inactivation of YME1L1 results in increased transfer of mtDNA in the nuclear genome. CONCLUSIONS: Our study demonstrates increased somatic transfer of mtDNA in colorectal tumors. Our study also reveals sex-based differences in frequency of NUMT occurrence and that NUMT in blood reflects NUMT in tumors, suggesting NUMT may be used as a biomarker for tumorigenesis. We identify YME1L1 as the first NUMT suppressor gene in human and demonstrate that inactivation of YME1L1 induces migration of mtDNA to the nuclear genome. Our study reveals that numtogenesis plays an important role in the development of cancer.

Complete Mitochondrial Genomes of Baikal Oilfishes (Perciformes: Cottoidei), Earth's Deepest-Swimming Freshwater Fishes.

Sculpins are predominantly benthic sit-and-wait predators that inhabit marine and freshwaters of the Northern Hemisphere. In striking contrast to riverine relatives, sculpins endemic to Lake Baikal have diversified in both form and function, with multiple taxa having adaptations for pelagic and bathyal niches within the world's deepest lake. Baikal Oilfishes (Comephorus spp.) represent a highly apomorphic taxon with unique skeletal morphology, soft anatomy, and reproductive ecology. Selection for novel behavior and life history may be evident in genes responsible for organismal energy balance, including those encoding subunits of the electron transport chain. Complete mitochondrial genomes were sequenced for the Big Baikal Oilfish (Comephorus baicalensis) and Little Baikal Oilfish (Comephorus dybowskii). Mitochondrial genomes encode genes essential for electron transport, and data provided here will complement ongoing investigations of genome-to-phenome maps for teleost respiration and metabolism. Phylogenetic analyses including oilfish mitogenomes and all publicly available cottoid representative sequences are largely concordant with previous studies.

Complete mitochondrial genomes for Cottus asper, Cottus perifretum, and Cottus rhenanus (Perciformes, Cottidae).

Freshwater sculpins represent a diverse but poorly-understood constituent of the Holarctic ichthyofauna. Sculpins are considered sensitive to pollution and habitat change, serving as aquatic bioindicators in ecotoxicology. Many species are protected by conservation agencies, due to anthropogenic activity within restricted geographic distributions. Here, we provide the first complete mitochondrial DNA sequences for three freshwater sculpins (Cottus asper, C. perifretum, C. rhenanus). These data are used to infer an updated mtDNA phylogeny for the genus Cottus, which supports results of previous research. These data are likely to be useful for future studies in biogeography, conservation, and functional genomics.