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.

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.

Interspecific relationships and the evolution of sexual dimorphism in pygmy sunfishes (Centrarchidae: Elassoma).

The genus Elassoma represents a small but unique component of the aquatic biodiversity hotspot in southeastern North America. We present the first phylogeny of the seven described species, corroborated by sequence data from mitochondrial and nuclear protein coding genes. This analysis reveals a Coastal Plain clade sister to the geographically isolated, and federally protected, Elassoma alabamae. The Coastal Plain clade contains the widespread E. zonatum, which is sister to a clade primarily restricted to lowland Neogene subprovinces. We analyzed morphometric data in a phylogenetic context to illustrate the evolution of sexual shape dimorphism within the genus. Sixteen univariate and three multivariate traits were tested for significant sexual dimorphism for each species, and relative transformation rates were inferred from the time tree. A simple index of interspecific sexual dimorphism revealed greater disparity among sympatric species comparisons than among allopatric comparisons. Results implicate geology as a primary factor influencing ecological diversification, and sexual selection as a mechanism reinforcing reproductive isolation in areas of secondary contact. We discuss putative roles of geological history and sexual selection in the generation and maintenance of the aquatic biodiversity gradient in southeastern North America.

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.

Ecological and evolutionary perspectives advance understanding of mycobacterial diseases.

Predicting the outbreak of infectious diseases and designing appropriate preventive health actions require interdisciplinary research into the processes that drive exposure to and transmission of disease agents. In the case of mycobacterial diseases, the epidemiological understanding of the scientific community hitherto was based on the clinical studies of infections in vertebrates. To evaluate the information gained by comprehensively accounting for the ecological and evolutionary constraints, we conducted literature searches assessing the role of mycobacteria interactions with non-vertebrate species in the origin of their pathogenicity and variations in disease risk. The reviewed literature challenges the current theory of person-to-person transmission for several mycobacterial infections. Furthermore, the findings suggest that diverse non-vertebrate organisms influence virulence, mediate transmission, and contribute to pathogen abundance in relation to vertebrate exposure. We advocate that an ecological and evolutionary framework provides novel insights to support a more comprehensive understanding of the prevention and management of diseases in vertebrates.

Paleoclimatic modeling and phylogeography of least killifish, Heterandria formosa: insights into Pleistocene expansion-contraction dynamics and evolutionary history of North American Coastal Plain freshwater biota.

BACKGROUND: Climatic and sea-level fluctuations throughout the last Pleistocene glacial cycle (~130-0 ka) profoundly influenced present-day distributions and genetic diversity of Northern Hemisphere biotas by forcing range contractions in many species during the glacial advance and allowing expansion following glacial retreat ('expansion-contraction' model). Evidence for such range dynamics and refugia in the unglaciated Gulf-Atlantic Coastal Plain stems largely from terrestrial species, and aquatic species Pleistocene responses remain relatively uninvestigated. Heterandria formosa, a wide-ranging regional endemic, presents an ideal system to test the expansion-contraction model within this biota. By integrating ecological niche modeling and phylogeography, we infer the Pleistocene history of this livebearing fish (Poeciliidae) and test for several predicted distributional and genetic effects of the last glaciation. RESULTS: Paleoclimatic models predicted range contraction to a single southwest Florida peninsula refugium during the Last Glacial Maximum, followed by northward expansion. We inferred spatial-population subdivision into four groups that reflect genetic barriers outside this refuge. Several other features of the genetic data were consistent with predictions derived from an expansion-contraction model: limited intraspecific divergence (e.g. mean mtDNA p-distance = 0.66%); a pattern of mtDNA diversity (mean Hd = 0.934; mean π = 0.007) consistent with rapid, recent population expansion; a lack of mtDNA isolation-by-distance; and clinal variation in allozyme diversity with higher diversity at lower latitudes near the predicted refugium. Statistical tests of mismatch distributions and coalescent simulations of the gene tree lent greater support to a scenario of post-glacial expansion and diversification from a single refugium than to any other model examined (e.g. multiple-refugia scenarios). CONCLUSIONS: Congruent results from diverse data indicate H. formosa fits the classic Pleistocene expansion-contraction model, even as the genetic data suggest additional ecological influences on population structure. While evidence for Plio-Pleistocene Gulf Coast vicariance is well described for many freshwater species presently codistributed with H. formosa, this species demography and diversification departs notably from this pattern. Species-specific expansion-contraction dynamics may therefore have figured more prominently in shaping Coastal Plain evolutionary history than previously thought. Our findings bolster growing appreciation for the complexity of phylogeographical structuring within North America's southern refugia, including responses of Coastal Plain freshwater biota to Pleistocene climatic fluctuations.

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).

Nuclear gene-inferred phylogenies resolve the relationships of the enigmatic Pygmy Sunfishes, Elassoma (Teleostei: Percomorpha).

Elassoma, the Pygmy Sunfishes, has long proven difficult to classify among the more than 15,000 species of percomorph fishes. Hypotheses dating to the 19th Century include Elassoma in Centrarchidae or in the monogeneric Elassomatidae, and more recent phylogenetic hypotheses have classified Elassoma in Smegmamorpha that also contained Synbranchiformes, Mugiliformes, Gasterosteiformes, and Atherinomorpha. No published phylogenetic analysis of morphological or molecular data has supported the monophyly of Smegmamorpha, or a consistent resolution of Elassoma relationships. In this study, we investigated the phylogenetic relationships of Elassoma and test the monophyly of Smegmamorpha with a nucleotide dataset comprising 10 protein-coding nuclear genes sampled from 65 percomorph species. Maximum likelihood analyses of each individual gene and the concatenated 10 genes all result in strong support for a clade composed of Elassoma and Centrarchidae, and no analysis supports monophyly of Smegmamorpha. Based on these results, a rank-free phylogenetic definition of Centrarchidae is presented that includes Elassoma, and the continued recognition of Smegmamorpha is discouraged. We discuss the implications of these phylogenetic analyses for relationships of several other percomorph lineages, including Kyphosidae, Terapontidae, Kuhliidae, Cheilodactylidae, Percichthyidae, Howellidae, Enoplosidae, Sinipercidae, and Cirrhitidae.

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.

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.

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.

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.

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.

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.

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.

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.

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.