Michael W. Sandel

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.

A method for assessing mitochondrial bioenergetics in whole white adipose tissues

Obesity is a primary risk factor for numerous metabolic diseases including metabolic syndrome, type II diabetes (T2DM), cardiovascular disease and cancer. Although classically viewed as a storage organ, the field of white adipose tissue biology is expanding to include the consideration of the tissue as an endocrine organ and major contributor to overall metabolism. Given its role in energy production, the mitochondrion has long been a focus of study in metabolic dysfunction and a link between the organelle and white adipose tissue function is likely. Herein, we present a novel method for assessing mitochondrial bioenergetics from whole white adipose tissue. This method requires minimal manipulation of tissue, and eliminates the need for cell isolation and culture. Additionally, this method overcomes some of the limitations to working with transformed and/or isolated primary cells and allows for results to be obtained more expediently. In addition to the novel method, we present a comprehensive statistical analysis of bioenergetic data as well as guidelines for outlier analysis.

Migration of mitochondrial DNA in the nuclear genome of colorectal adenocarcinoma

BackgroundColorectal 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.MethodsWhole-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.ResultsOur 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.ConclusionsOur 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.

Aging and energetics’ ‘Top 40’ future research opportunities 2010-2013

Background: As part of a coordinated effort to expand our research activity at the interface of Aging and Energetics a team of investigators at The University of Alabama at Birmingham systematically assayed and catalogued the top research priorities identified in leading publications in that domain, believing the result would be useful to the scientific community at large. Objective: To identify research priorities and opportunities in the domain of aging and energetics as advocated in the 40 most cited papers related to aging and energetics in the last 4 years. Design: The investigators conducted a search for papers on aging and energetics in Scopus, ranked the resulting papers by number of times they were cited, and selected the ten most-cited papers in each of the four years that include 2010 to 2013, inclusive. Results: Ten research categories were identified from the 40 papers. These included: (1) Calorie restriction (CR) longevity response, (2) role of mTOR (mechanistic target of Rapamycin) and related factors in lifespan extension, (3) nutrient effects beyond energy (especially resveratrol, omega-3 fatty acids, and selected amino acids), 4) autophagy and increased longevity and health, (5) aging-associated predictors of chronic disease, (6) use and effects of mesenchymal stem cells (MSCs), (7) telomeres relative to aging and energetics, (8) accretion and effects of body fat, (9) the aging heart, and (10) mitochondria, reactive oxygen species, and cellular energetics. Conclusion: The field is rich with exciting opportunities to build upon our existing knowledge about the relations among aspects of aging and aspects of energetics and to better understand the mechanisms which connect them.

The Utility of Mitochondrial and Y Chromosome Phylogenetic Data to Improve Correction for Population Stratification

Genome-wide association (GWA) studies have become a standard approach for discovering and validating genomic polymorphisms putatively associated with phenotypes of interest. Accounting for population structure in GWA studies is critical to attain unbiased parameter measurements and control Type I error. One common approach to accounting for population structure is to include several principal components derived from the entire autosomal dataset, which reflects population structure signal. However, knowing which components to include is subjective and generally not conclusive. We examined how phylogenetic signal from mitochondrial DNA (mtDNA) and chromosome Y (chr:Y) markers is concordant with principal component data based on autosomal markers to determine whether mtDNA and chr:Y phylogenetic data can help guide principal component selection. Using HAPMAP and other original data from individuals of multiple ancestries, we examined the relationships of mtDNA and chr:Y phylogenetic signal with the autosomal PCA using best subset logistic regression. We show that while the two approaches agree at times, this is independent of the component order and not completely represented in the Eigen values. Additionally, we use simulations to demonstrate that our approach leads to a slightly reduced Type I error rate compared to the standard approach. This approach provides preliminary evidence to support the theoretical concept that mtDNA and chr:Y data can be informative in locating the PCs that are most associated with evolutionary history of populations that are being studied, although the utility of such information will depend on the specific situation.

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

Abstract 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.

Complete mitochondrial genome sequences of five rockfishes (Perciformes: Sebastes)

Abstract Rockfishes of the genus Sebastes rank among the longest-lived vertebrate animals. In order to facilitate comparative genomic research in animal longevity, the complete mitochondrial genome sequences are presented for Sebastes aleutianus, Sebastes minor, Sebastes nigrocinctus, Sebastes rubrivinctus, and Sebastes steindachneri.

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

ABSTRACT 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.

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

Abstract 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.