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Phelps, M. P.

Publications and source records attributed to Phelps, M. P..

5 recordsLinked to original sources

Characterization of transcriptomic profiles underlying gross morphological changes observed in semelparous pink salmon (Oncorhynchus gorbuscha)

Pacific salmon (Oncorhynchus spp.) undergo intricate physiological changes during maturation as they migrate to spawning beds and breed before succumbing to a programmed senescence (semelparous life cycle). Research into the physiological mechanisms of semelparity in salmon has identified a clear and progressive rise in sex and stress hormone levels throughout their migration, which correlates with the emergence of morphological traits, as well as changes in behavioral patterns. We examined transcriptional changes in three critical tissues (gonads, head kidney, and skeletal muscle) across the spawning migration in male and female Pink salmon (Oncorhynchus gorbuscha) to capture the molecular changes occurring in these tissues during maturation and senescence. Major transcriptional changes occurred around the time of spawning, while only modest transcriptional changes were found as the fish migrated between saltwater and freshwater. Examination of enriched biological pathways identified the signatures of semelparous catabolic processes in all tissues and a strong immune response in somatic tissues. Evidence of shifts in lipid energy mobilization were also seen in somatic tissues. A closer investigation of the expression patterns of endocrine hormone receptors showed that many endocrine pathways prioritized expression of specific dominant ohnologs to orchestrate much of the hormone response in the analyzed tissues. Our characterization of the transcriptional profiles in migrating pink salmon adds critical context to link the molecular changes occurring in tissues to the physiological transitions that define semelparous maturation in Pacific salmon. NEW & NOTEWORTHYLarge transcriptional changes occurred in the gonads, head kidney, and skeletal muscle of pink salmon during the final stages of their spawning migration. Across the tissues and sexes, spawning was marked by coordinated activation of catabolic programs (autophagy, proteolysis, cell death), and a strong immune response in somatic tissues, alongside lipid mobilization. Endocrine receptor expression analyses revealed that the response to hormones was primarily mediated by a limited number of dominant ohnologs.

physiology↗

Local Thermal Adaptation occurs via Modulation of Mitochondrial Activity in Chinook Salmon

Freshwater and anadromous fish have been identified as one of the most at-risk groups threatened by climate induced warming given their metabolic dependence on environmental temperature and limited ability to track favorable environmental conditions. The future of these fish will depend on their ability to adapt to new thermal regimes over biologically relevant timescales. However, the mechanistic understanding of temperature responses required to predict if adaption can keep pace with climate change is limited. To address this question, we investigated the mechanistic basis of thermal adaptation across multiple levels of biological organization in the iconic and endangered Chinook Salmon (Oncorhynchus tshawytscha). We uncovered a mechanistic basis of thermal adaptation centered on the thermal responsiveness of mitochondrial function which modulates the extent to which rising temperatures increase metabolic demand on the cardio-respiratory system. These insights demonstrate that the populations studied here are able to maintain high levels of physiological performance at temperatures several degrees above historic averages, indicating that the decline Chinook Salmon and failure to recover despite conservation efforts is unlikely to be due to increased temperatures as a consequence of climate change.

evolutionary biology↗

Gene function is a driver of signaling pathway evolution following whole genome 5 duplication

The genome of many plant and animal species are heavily influenced by ancestral whole genome duplication (WGD) events. These events transform the regulation and function of gene networks, yet the evolutionary forces at work on duplicated genomes are not fully understood. Genes involved in cell surface signaling pathways are commonly retained following WGD. To understand the mechanisms driving functional evolution of duplicated cell signaling pathways, we performed the activin receptor signaling pathway in rainbow trout (RBT). Rainbow trout are a model salmonid species that exhibit a duplicated genome as a result of an ancestral WGD that occurred in all teleost fish, and a second more recent WGD found in salmonid fishes. This makes RBT a powerful system for studying ohnolog evolution in a single species. We observed that regulation of the duplicated activin receptor signaling pathway is commonly driven by tissue-specific expression of inhibitors and ligands along with the subfunctionalization of ligand ohnologs. Evidence suggests that for inhibitors and R-Smad signaling molecules, there is ongoing pressure to establish a single copy state which may be driven, in part, by regulatory suppression of select ohnologs. The core transmembrane receptors and Co-Smad signaling cascade members are high duplicated yet exhibit contrasting expression dynamics where receptors tend to share expression across tissues while dominance of a single ohnolog is common for the Smad4, Co-Smad gene family. Our findings provide support for a generalized model where gene function and gene dosage have a complementary role in ohnolog evolution following WGD.

evolutionary biology↗

New human chromosomal safe harbor sites for genome engineering with CRISPR/Cas9, TAL effector and homing endonucleases

Safe Harbor Sites (SHS) are genomic locations where new genes or genetic elements can be introduced without disrupting the expression or regulation of adjacent genes. We have identified 35 potential new human SHS in order to substantially expand SHS options beyond the three widely used canonical human SHS, AAVS1, CCR5 and hROSA26. All 35 potential new human SHS and the three canonical sites were assessed for SHS potential using 9 different criteria weighted to emphasize safety that were broader and more genomics-based than previous efforts to assess SHS potential. We then systematically compared and rank-ordered our 35 new sites and the widely used human AAVS1, hROSA26 and CCR5 sites, then experimentally validated a subset of the highly ranked new SHS together versus the canonical AAVS1 site. These characterizations included in vitro and in vivo cleavage-sensitivity tests; the assessment of population-level sequence variants that might confound SHS targeting or use for genome engineering; homology-dependent and -independent, SHS-targeted transgene integration in different human cell lines; and comparative transgene integration efficiencies at two new SHS versus the canonical AAVS1 site. Stable expression and function of new SHS-integrated transgenes were demonstrated for transgene-encoded fluorescent proteins, selection cassettes and Cas9 variants including a transcription transactivator protein that were shown to drive large deletions in a PAX3/FOXO1 fusion oncogene and induce expression of the MYF5 gene that is normally silent in human rhabdomyosarcoma cells. We also developed a SHS genome engineering toolkit to enable facile use of the most extensively characterized of our new human SHS located on chromosome 4p. We anticipate our newly identified human SHS, located on 16 chromosomes including both arms of the human X chromosome, will be useful in enabling a wide range of basic and more clinically-oriented human gene editing and engineering.

genomics↗

DEVELOPMENTAL DYNAMICS OF GREEN FLUORESCENT CHROMATOPHORES IN THE DAGGERBLADE GRASS SHRIMP, PALAEMONETES PUGIO HOLTHUIS, 1949 (DECAPODA, CARIDEA, PALAEMONIDAE)

The daggerblade grass shrimp, Palaemonetes pugio Holthuis 1949 relies heavily on transparency as the primary form of camouflage yet possess several types of pigmented chromatophores located throughout the body. A distinct sub-population of yellow/white chromatophores have been discovered to exhibit brilliant green fluorescence. These cells develop in the embryo and are the primary chromatophore present in larval organisms. Post-larval grass shrimp undergo a major restructuring of the pattern and morphology of fluorescent chromatophores after metamorphosis with chromatophores found uniformly distributed throughout the body and at high concentration on the hepatopancreas and the eye stalks. In adult P. pugio the number of fluorescent chromatophores is significantly reduced and fluorescence is limited to only a subset of these chromatophores. The novel fluorescent properties of these cells, there relatively high abundance during early life stages, and pattern of development, suggest important cellular functions for these fluorescent chromatophores in grass shrimp.

developmental biology↗