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1. The Long-Term Effects of Developmental Hypoxia on Cardiac Mitochondrial Function in Snapping Turtles

   https://doi.org/10.3389/fphys.2021.689684  

   Galli, Gina L. ; Ruhr, Ilan M. ; Crossley, Janna ; Crossley, Dane A. ( June 2021 , Frontiers in Physiology)

   It is well established that adult vertebrates acclimatizing to hypoxic environments undergo mitochondrial remodeling to enhance oxygen delivery, maintain ATP, and limit oxidative stress. However, many vertebrates also encounter oxygen deprivation during embryonic development. The effects of developmental hypoxia on mitochondrial function are likely to be more profound, because environmental stress during early life can permanently alter cellular physiology and morphology. To this end, we investigated the long-term effects of developmental hypoxia on mitochondrial function in a species that regularly encounters hypoxia during development—the common snapping turtle ( Chelydra serpentina ). Turtle eggs were incubated in 21% or 10% oxygen from 20% of embryonic development until hatching, and both cohorts were subsequently reared in 21% oxygen for 8 months. Ventricular mitochondria were isolated, and mitochondrial respiration and reactive oxygen species (ROS) production were measured with a microrespirometer. Compared to normoxic controls, juvenile turtles from hypoxic incubations had lower Leak respiration, higher P:O ratios, and reduced rates of ROS production. Interestingly, these same attributes occur in adult vertebrates that acclimatize to hypoxia. We speculate that these adjustments might improve mitochondrial hypoxia tolerance, which would be beneficial for turtles during breath-hold diving and overwintering in anoxic environments.
2. Random field modeling of multi-trait multi-locus association for detecting methylation quantitative trait loci

   https://doi.org/10.1093/bioinformatics/btac443  

   Lyu, Chen ; Huang, Manyan ; Liu, Nianjun ; Chen, Zhongxue ; Lupo, Philip J. ; Tycko, Benjamin ; Witte, John S. ; Hobbs, Charlotte A. ; Li, Ming ; Marschall, ed., Tobias ( July 2022 , Bioinformatics)

   CpG sites within the same genomic region often share similar methylation patterns and tend to be co-regulated by multiple genetic variants that may interact with one another.

   We propose a multi-trait methylation random field (multi-MRF) method to evaluate the joint association between a set of CpG sites and a set of genetic variants. The proposed method has several advantages. First, it is a multi-trait method that allows flexible correlation structures between neighboring CpG sites (e.g. distance-based correlation). Second, it is also a multi-locus method that integrates the effect of multiple common and rare genetic variants. Third, it models the methylation traits with a beta distribution to characterize their bimodal and interval properties. Through simulations, we demonstrated that the proposed method had improved power over some existing methods under various disease scenarios. We further illustrated the proposed method via an application to a study of congenital heart defects (CHDs) with 83 cardiac tissue samples. Our results suggested that gene BACE2, a methylation quantitative trait locus (QTL) candidate, colocalized with expression QTLs in artery tibial and harbored genetic variants with nominal significant associations in two genome-wide association studies of CHD.

   https://github.com/chenlyu2656/Multi-MRF.

   Supplementary data are available at Bioinformatics online.
3. Incubation temperature and satiety influence general locomotor and exploratory behaviors in the common snapping turtle (Chelydra serpentina)

   Miller, Soleille ; Derenne, Adam ; Ellis-Felege, Susan ; Rhen, Turk ( March 2020 , Physiology behavior)

   Temperature during embryogenesis determines sex and has been shown to influence other physiological traits in reptiles. The common snapping turtle (Chelydra serpentina) is an ideal model for testing how temperature impacts behavior in species that display temperature-dependent sex determination. Behavioral assays are crucial to understanding how a changing climate may affect whole organism function in the snapping turtle. Currently, there are few behavioral assays for semi-aquatic vertebrates like turtles. In this study, we used digital cameras to record behavior of fed and fasted hatchling turtles from different incubation temperatures in an open field setting for 20 minutes in 2018 and repeated the experiment in 2019. Open fields were circular tanks filled with water to a depth of 3.5 cm. Each field was split into four quadrants and two zones (inner and outer). The amount of time turtles spent actively moving, total distance travelled, and several other measures were collected and summarized automatically from videos with open source image analysis software (ImageJ). Satiety and incubation temperature had significant effects on total distance moved, time spent moving, and time moving in the outer zone. These findings indicate that temperature during embryogenesis has a long-lasting effect on neural mechanisms underlying exploratory or generalmore »locomotor behavior in turtles.« less
4. Draft Genome of the Common Snapping Turtle, Chelydra serpentina , a Model for Phenotypic Plasticity in Reptiles

   https://doi.org/10.1534/g3.120.401440  

   Das, Debojyoti ; Singh, Sunil Kumar ; Bierstedt, Jacob ; Erickson, Alyssa ; Galli, Gina L ; Crossley, Dane A ; Rhen, Turk ( December 2020 , G3 Genes|Genomes|Genetics)

   Abstract Turtles are iconic reptiles that inhabit a range of ecosystems from oceans to deserts and climates from the tropics to northern temperate regions. Yet, we have little understanding of the genetic adaptations that allow turtles to survive and reproduce in such diverse environments. Common snapping turtles, Chelydra serpentina, are an ideal model species for studying adaptation to climate because they are widely distributed from tropical to northern temperate zones in North America. They are also easy to maintain and breed in captivity and produce large clutch sizes, which makes them amenable to quantitative genetic and molecular genetic studies of traits like temperature-dependent sex determination. We therefore established a captive breeding colony and sequenced DNA from one female using both short and long reads. After trimming and filtering, we had 209.51Gb of Illumina reads, 25.72Gb of PacBio reads, and 21.72 Gb of Nanopore reads. The assembled genome was 2.258 Gb in size and had 13,224 scaffolds with an N50 of 5.59Mb. The longest scaffold was 27.24Mb. BUSCO analysis revealed 97.4% of core vertebrate genes in the genome. We identified 3.27 million SNPs in the reference turtle, which indicates a relatively high level of individual heterozygosity. We assembled the transcriptome usingmore »RNA-Seq data and used gene prediction software to produce 22,812 models of protein coding genes. The quality and contiguity of the snapping turtle genome is similar to or better than most published reptile genomes. The genome and genetic variants identified here provide a foundation for future studies of adaptation to climate.« less
5. Comprehensive analysis of TCGA data reveals correlation between DNA methylation and alternative splicing

   https://doi.org/10.1186/s12864-022-08992-w  

   Lin, Shuting ; Yi, Soojin ; Qiu, Peng ( November 2022 , BMC Genomics)

   The effect of DNA methylation on the regulation of gene expression has been extensively discussed in the literature. However, the potential association between DNA methylation and alternative splicing is not understood well. In this study, we integrated multiple omics data types from The Cancer Genome Atlas (TCGA) and systematically examined the relationship between DNA methylation and alternative splicing. Using the methylation data and exon expression data, we identified many CpG sites significantly associated with exon expression in various types of cancers. We further observed that the direction and strength of significant CpG-exon correlation tended to be consistent across different cancer contexts, indicating that some CpG-exon correlation patterns reflect fundamental biological mechanisms that transcend tissue- and cancer- types. We also discovered that CpG sites correlated with exon expressions were more likely to be associated with patient survival outcomes compared to CpG sites that did not correlate with exon expressions. Furthermore, we found that CpG sites were more strongly correlated with exon expression than expression of isoforms harboring the corresponding exons. This observation suggests that a major effect of CpG methylation on alternative splicing may be related to the inclusion or exclusion of exons, which subsequently impacts the relative usage ofmore »various isoforms. Overall, our study revealed correlation patterns between DNA methylation and alternative splicing, which provides new insights into the role of methylation in the transcriptional process.

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