Anthony Farrell

Professor

Relevant Degree Programs

 

Graduate Student Supervision

Doctoral Student Supervision (Jan 2008 - May 2019)
Physiological, transcriptomic and genomic mechanisms of thermal adaptation in Oncorhynchus mykiss (2017)

Given the rate and magnitude of the ongoing global warming, there is some urgency to understand the underlying mechanism of thermal adaptation to evaluate and predict the ecological consequences. This thesis used Oncorhynchus mykiss from different thermal regimes to examine thermal adaptation at physiological, transcriptomic and genomic levels. Thermal tolerance was examined in three redband trout (O. mykiss gairdneri) populations from warm desert and cool montane climates (Idaho, USA), as well as in a domesticated rainbow trout (O. mykiss) strain raised in a thermally challenging environment for over 19 generations (Western Australia, Australia). Acclimated to 15°C, the desert redband trout had the highest critical thermal maximum (CTMAX; 29.7°C) and maintained an almost constant absolute aerobic scope (AAS) across a broader range of test temperatures (12-24°C) than seen in other strains, but had the lowest peak AAS, suggesting a tradeoff between thermal performance and tolerance. Western Australian rainbow trout had the highest AAS, even when tested at 21°C, which may be a result of hatchery selection for thermal performance. Although the rate transition temperatures for maximum heart rate (Arrhenius breakpoint and arrhythmia temperature for fH,max) were similar among all populations, fH,max was the highest in the desert redband trout population at all temperatures. Cardiac RNA sequencing revealed different patterns of gene regulation among redband trout populations during acute warming. Many genes had different mRNA abundances between populations due to constitutive and induced expression, and the number of differentially expressed genes among populations was positively correlated to the genetic distance, suggesting intraspecific cellular regulatory strategies in response to acute warming. Population and quantitative genetic studies identified potential genomic markers for thermal adaptation. A total of twenty-one loci were putatively under positive thermal selection (“outliers”). In addition, genotypes of some outlier loci had significantly different CTMAX. Genome-wide association study identified twelve loci that were significantly associated with individual CTMAX. Altogether, results in my dissertation demonstrated the capacity of thermal adaptation in O. mykiss populations at multiple organismal levels. This data lays a foundation to improve our understanding on the potential impact of global warming on wild aquatic populations.

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Upper thermal limits and acclimation potential of Arctic cod (Boreogadus saida) : a key food web species in the Arctic Ocean (2017)

The recent rapid and unprecedented changes to the physical and biogeochemical properties of the Arctic Ocean have gained worldwide attention. The greater than 50% reduction in sea ice volume below average is of great concern. My thesis investigates the potential effects of a warmer Arctic Ocean upon the indigenous Arctic cod, Boreogadus saida. This fish make up a significant proportion of the lower trophic energy reserve available in Arctic marine systems. Predators rely upon Arctic cod to provide them bite sized access to those critical energy reserves. Yet despite their key role in the Arctic food web, their upper thermal limits are not well studied. Thus, my three objectives were: a) quantify, for the first time in this species, their upper thermal limits b) determine the acclimation potential of the species at three acclimation temperatures and c) contrast the results generated by different methods that quantify thermal limits for declining physiological performance (rate transition temperatures) that I determined.Boreogadus saida upper thermal limits were tested under acute warming conditions using three different methods: loss of equilibrium (Tcmax), absolute aerobic scope (AAS) derived from oxygen uptake rates and the cardiac method, which uses maximum heart rate (ƒHmax) to detect change in whole animal performance. In conducting the thermal acclimation studies, I discovered foremost that 6.5°C-acclimated fish grew at that temperature but, to date, have only produced eggs at 3.5°C water temperatures. The Tcmax significantly increased with acclimation temperature (0.5, 3.5 and 6.5°C) from 14.4, 15.5, up to 17.1°C respectively, while the more ecologically relevant AAS transition temperature limits were found at lower temperatures from 1.0 to 5.5°C. The temperature for peak ƒHmax (Tmax) occurred between 11.0 to 12.0°C and the performance of ƒHmax for larval B. saida during acute warming was not significantly different from the adults until Tmax was reached. This novel study of the thermal physiology of this key Arctic marine food web species revealed a greater than expected thermal tolerance and a significant acclimation potential up to 6.5°C, suggesting that this species may be more resilient to rapid climate change than previously thought.

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Cardiorespiratory responses to hypoxia in high- and low-altitude geese and ducks (2016)

High-altitude (HA) life is challenging due to the reduced partial pressure of oxygen (hypoxia). Hence, HA vertebrates have evolved increased capacities in their oxygen transport cascade enhancing oxygen transfer. The extent of interspecies variation in these responses within waterfowl, a taxon prolific at HA, remains largely unknown. This thesis investigated 17 waterfowl groups at different altitudes to address the overarching hypotheses that waterfowl use multiple cardiorespiratory strategies to maintain oxygen supply during hypoxia, and that HA exposure alters the waterfowl hypoxic ventilatory and cardiovascular responses. A comprehensive analysis of metabolic, cardiovascular, and ventilatory responses to progressive decreases in equivalent fractional composition of inspired oxygen was made on resting low-altitude (LA) barnacle geese, LA bar-headed geese, HA bar-headed geese, Andean geese, and crested ducks. Andean geese and crested ducks, lifelong HA residents, exhibited fundamentally different mechanisms for maintaining oxygen supply during hypoxia than bar-headed geese, transient HA migrators. Bar-headed geese robustly increased ventilation and heart rate, whereas Andean species increased lung oxygen extraction and stroke volume. Also, HA-reared bar-headed geese exhibited reduced oxygen consumption during hypoxia compared to LA-reared bar-headed geese. Similar cardiovascular studies were performed on five HA duck species (yellow-billed pintail, cinnamon teal, ruddy duck, speckled teal, and Puna teal) in Peru and six related LA duck species (northern pintail, cinnamon teal, ruddy duck, green-winged teal, gadwall, and mallard duck) in the USA. Heart rate and oxygen pulse remained generally unchanged. Instead, most HA ducks exhibited higher blood-oxygen carrying capacity and lower heart rate variability than LA ducks. While heart rate, stroke volume, oxygen pulse, and blood-oxygen carrying capacity contributed to all 17 groups’ hypoxic cardiovascular responses, the predominant responses were increased stroke volume and, in HA taxa, blood-oxygen carrying capacity. Only bar-headed geese increased heart rate appreciably.This thesis identifies multiple cardiovascular and respiratory strategies by which waterfowl maintain oxygen supply during hypoxia, and provides insight into how HA rearing impacts these responses. This thesis also suggests that short-term HA performance utilizes primarily functional enhancements (e.g. rapid heart rate and ventilation increases), whereas lifelong HA residency is supported predominantly by structural changes (e.g. lung and cardiac morphology enhancements).

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The functional significance and evolution of the coronary circulation in sharks (2016)

The coronary circulation first appeared in the chordate lineage in cartilaginous fishes where it perfuses the entire myocardium, just like in birds and mammals but unlike in most teleost fishes. Yet, despite the pivotal position of elasmobranchs in the evolution of the coronary oxygen supply, the functional significance of their coronary circulation has never been investigated. Elasmobranchs are of special interest because of the morphological arrangement of their cardiomyocytes, which has resulted in the majority of the ventricular myocardium having access to oxygen from both a coronary supply and the venous blood returning to the heart. In order to determine the relative contribution of the coronary oxygen supply to cardiovascular function, I measured coronary blood flow (CBF) in the sandbar shark, Carcharhinus plumbeus, and leopard shark, Triakis semifasciata, while manipulating cardiovascular status using pharmacological approaches and in vivo temperature changes, respectively. By exploring inter- and intra-individual variation in cardiovascular variables I show that coronary blood flow is directly related to heart rate in both bradycardic (R²= 0.6, P
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Cardiac control in the Pacific hagfish (Eptatretus stoutii) (2014)

The Pacific hagfish (Eptatretus stoutii), being an extant ancestral craniate, possesses the most ancestral craniate-type heart with valved chambers, a response to increased filling pressure with increased stroke volume (Frank-Starling mechanism), and myogenic contractions. Unlike all other known craniate hearts, this heart receives no direct neural stimulation. Despite this, heart rate can vary four-fold during a prolonged, 36-h anoxic challenge followed by a normoxic recovery period, with heart rate decreasing in anoxia, and increasing beyond routine rates during recovery, a remarkable feat for an aneural heart. This thesis is a study of how the hagfish can regulate heart rate without the assistance of neural stimulation.A major role of hyperpolarization-activated cyclic nucleotide-activated (HCN) channels in heartbeat initiation was indicated by pharmacological application of zatebradine to spontaneously contracting, isolated hearts, which stopped atrial contraction and vastly reduced ventricular contraction. Tetrodotoxin inhibition of voltage-gated Na⁺ channels induced an atrioventricular block suggesting these channels play a role in cardiac conduction.Partial cloning of HCN channel mRNA extracted from hagfish hearts revealed six HCN isoforms, two hagfish representatives of vertebrate HCN2 (HCN2a and HCN2b), three of HCN3 (HCN3a, HCN3b and HCN3c) and one HCN4. Two paralogs of HCN3b were discovered, however, HCN3a dominated the expression of HCN isoforms followed by HCN4. All HCN isoforms bar HCN3b were dominantly expressed in the atrium, likely to support greater atrial excitability ensuring synchronous contractions. Phylogenetic analysis suggested that HCN3 is the ancestral isoform supporting previous observations.Studies with β-adrenoreceptor agonists and antagonists in isolated, spontaneously beating hearts showed that the routine normoxic heart rate may involve maximal catecholamine stimulation of heart rate through cAMP stimulation of HCN channels via transmembrane adenylyl cyclase (tmAC). Loss of this tonic β-adrenorecptor cardiac stimulation during anoxia reduces heart rate, but restoring β-adrenoreceptor stimulation during normoxic recovery does not produce the previously observed increase above routine heart rate in vivo. Instead, bicarbonate-stimulated, soluble adenylyl cyclase (sAC) mediated cAMP production was found to produce this tachycardia in addition to the reinstated tmAC produced cAMP. This is the first time sAC has been implicated in heart rate control.

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Oxygen supply in rainbow trout (Oncorhynchus mykiss) and its ecological impacts : an investigation of poor triploid performance (2013)

Acquisition of environmental O₂ and its delivery throughout the body is essential for vertebrates and dictates habitat, life style, variation in anatomical form and function and even survival. Triploid (3N) rainbow trout (Oncorhynchus mykiss), which are important to the $0.5 billion British Columbia sport fishing industry, provide an informative model organism to study corporeal O₂ supply limitations and associated effects on survival in the wild. Triploid O₂ supply limitations likely stem from enlarged cells and contribute to poor 3N tolerance of sub-optimal conditions, which, in turn, may lead to high 3N population-level mortality rates in nature.Therefore, in order to test the hypotheses that corporeal O₂ supply limits aerobic performance of 3N rainbow trout and that aerobic performance, in turn, limits survival in the wild, I compared the cardiorespiratory physiology of diploid (2N) and 3N Blackwater River rainbow trout facing a high temperature challenge in the lab and survival in the wild. I then investigated the potential of a 3N cardiac O₂ supply deficiency, using a modified Krogh diffusion model, and discussed its significance to temperature tolerance, endurance swimming and survival in the wild. Both of my hypotheses were supported. A slower increase in 3N heart rate with warming suggested reduced O₂ convection through the body of 3N fish at high temperatures. Relating these results and endurance swimming rank with survival and habitat utilization in lakes revealed thermal tolerance and aerobic capacity as important variables influencing lake survival. The Krogh model showed 3N relative to 2N cardiac O₂ supply limitations that were primarily driven by reduced 3N arterial O₂ content, which I showed not to be caused by reduced 3N haemoglobin - O₂ affinity. In supporting the 2 main hypotheses of my thesis, this theoretically predicted 3N cardiac O₂ supply deficiency may explain reduced 3N aerobic swimming capacity and heart rate response to warming. Thus, my findings are consistent with corporeal O₂ supply limitations to high temperature tolerance and aerobic swimming capacity of 3N rainbow trout, both of which can limit survival in the wild, depending on the biotic and abiotic conditions and physiological state of the organism.

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Cardiorespiratory physiology and temperature tolerance among populations of sockeye salmon (Oncorhynchus nerka) (2011)

Elevated summer water temperature has been associated with high mortality in adult sockeye salmon (Oncorhynchus nerka) during their once-in-a-lifetime migration up the Fraser River (British Columbia, Canada) to their spawning grounds. There are over 100 genetically distinct populations of sockeye salmon in the Fraser River watershed, varying in migration distance, elevation gain, river temperature and river flow. This thesis studied the physiological basis for temperature tolerance in sockeye salmon and examined the overall hypothesis that each sockeye salmon population has physiologically adapted to meet their specific upriver migration conditions.Swimming and cardiorespiratory performance were compared over a range of temperatures across six wild, migrating adult sockeye salmon populations. All populations maintained maximum performance across the entire range of temperatures typically encountered during their upriver migration, with Chilko sockeye salmon emerging as the most high temperature-tolerant. In addition, populations with more challenging migrations had greater aerobic scope, larger hearts and improved coronary supply. These results suggest that sockeye salmon populations have physiologically adapted to cope with their local upriver migration conditions, despite never before having performed the upriver migration. Temperatures exceeding the population-specific thermal optimum resulted in severely impaired aerobic scope and swimming performance. This study suggests that population-specific thermal limits are set by physiological limitations in aerobic performance. Specifically, fish may be unable to swim at warm temperature due to insufficient oxygen supply to meet demand, triggered via a cardiac limitation due to reduced scope for heart rate.Given the key role of the heart in limiting thermal tolerance, the role of cardiac adrenergic stimulation was examined as a potential mechanism underlying the observed differences in thermal tolerance across sockeye salmon populations. Chilko sockeye salmon had a greater density of ventricular β-adrenoceptors, which may provide greater cardiac capacity and protection at temperature extremes, thereby expanding their breadth of thermal tolerance compared to other populations. This thesis suggests that sockeye salmon populations will be differentially affected by warming river temperatures, raising conservation concerns for biodiversity. This work provides important insight into local adaptation in sockeye salmon and identifies a possible cause for in-river mortality associated with warm temperatures in sockeye salmon.

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Master's Student Supervision (2010 - 2018)
Effects of bicarbonate on cardiac function in fish (2018)

An entirely novel mechanism to modulate heart rate was recently discovered in the Pacific hagfish (Eptatretus stoutii): a soluble adenylyl cyclase (sAC)-mediated pathway that increases cyclic adenosine monophosphate (cAMP) production upon stimulation by HCO₃₋ to increase heart rate. However, still unknown is whether this cardiac control pathway is present in other species as well. The objective of my study was to determine the effects of increasing extracellular [HCO₃₋] on the in vitro cardiac function of other fish species and whether the sAC-mediated pathway is associated with recovery of cardiac function during debilitating conditions. Exposure to severe hypoxia (100% N₂) and hypercapnic acidosis (7.5% or 15% CO₂) significantly decreased the heart rate of isolated, freely beating hearts and reduced the isometric tension (contractility) of electrically paced ventricular strips from Pacific lamprey (Lampetra richardsoni), Pacific spiny dogfish (Squalus suckleyi), Asian swamp eel (Monopterus albus), white sturgeon (Acipenser transmontanus), zebrafish (Danio rerio), and starry flounder (Platichthys stellatus). Spontaneous recovery in heart rate or contractility was not observed during severe hypoxia or hypercapnic acidosis for any of the species tested. Addition of HCO₃₋ (up to 50 mM) was associated with a complete and dose-dependent recovery of control heart rate in lamprey, dogfish, and swamp eel hearts during severe hypoxia, and in dogfish, sturgeon, and swamp eel hearts during hypercapnic acidosis. A partial recovery of control heart rate was observed in lamprey and zebrafish hearts during hypercapnic acidosis. However, HCO₃₋ had no effect on the heart rate or contractility in flounder hearts and had little to no effect on restoring control contractility in dogfish, swamp eel, and flounder ventricular strips.The addition of KH7 (sAC blocker) abolished the HCO₃₋-induced recovery of heart rate during severe hypoxia only in the lamprey heart. Thus, the sAC-mediated pathway in cardiac control appears to be unique to the cyclostomes and not present in the other species tested. While the sAC-mediated pathway was associated with the recovery of heart rate in the lamprey heart, the specific mechanisms behind how HCO₃₋ was associated with the recovery of heart rate in the other species still needs to be determined.

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Estimating aerobic and anaerobic capacities using the respiratory assessment paradigm : a validation using Atlantic salmon (Salmo salar) and European sea bass (Dicentrarchus Labrax) (2016)

Assessing fish performance, whether for extrapolation to natural conditions, culture conditions or toxicology, has a long history of using swim performance, metabolic rates and performance in hypoxia. However, rarely are these metrics unified in a test. Hence, thesis’ objective was to test a respiratory assessment paradigm (RAP), which comprehensively evaluated aerobic and anaerobic metabolism by explicitly measuring aerobic capacity, recovery and performance in hypoxia. To provide high fish throughput with each test, RAP used multiple intermittent-flow respirometry systems. I tested RAP by examining two practical questions: do aquaculture practices compromise the respiratory robustness of domesticated Atlantic salmon (Salmo salar) and, if so, how might it be reversed? Second, does an acute sub-lethal exposure to chemically dispersed oil have a chronic residual respiratory effect on European sea bass (Dicentrarchus labrax).RAP revealed a domesticated (Bolaks) strain of Atlantic salmon had a lower aerobic capacity than a wild (Lærdal) strain. Incremental exercise training significantly increased aerobic and recovery capacities in only the Lærdal strain. Thus, the Bolaks strain appeared to be athletically less robust than Lærdal strain. As a conclusion, ten generations of growth-oriented breeding program of Bolaks strain in commercial aquaculture have reduced its athletic robustness and cardiorespiratory plasticity as compared to their wild conspecifics. Given the success in improving athletic robustness of the wild strain, it still remains to explore whether an exercise- training protocol can be developed that will provide benefits to the salmon aquaculture industry. RAP discovered no residual effect of oil on aerobic capacity for either hypoxia tolerant (HT) or hypoxia sensitive (HS) sea bass. Instead, RAP discovered a residual effect for only the HT phenotype on its ability to survive in hypoxia, which was evidenced by an impaired tolerance to hypoxia and an increased oxygen deficit in hypoxia. Therefore, RAP identified a chronic impairment from acute exposure to oil to the hypoxia-tolerant segment of the sea bass population, perhaps increasing their risk of perishing in hypoxic episodes. These successful applications illustrate that RAP is a reliable methodology that could find further application to comparative studies of thermal, hypoxic and anthropogenic effects on the ecological performances of fishes.

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Maximum heart rate as a means of rapidly estimating optimal temperature for aerobic scope in salmon : its potential for application (2012)

Knowing the optimal temperature (Topt) for aerobic scope of fishes may be useful for predicting responses to warming environmental temperature because Topt is when fish can allocate the most oxygen to activity. However, the broad application of Topt measurements is hampered by the time required to determine Topt of a species. This thesis sought to develop a rapid method of estimating Topt of Pacific salmon species (genus Oncorhynchus) based on evidence that suggests the decline in aerobic scope above Topt is triggered by a limitation on maximum heart rate (fH). Thus, maximum fH at elevated temperature is thought to limit oxygen convection through the circulatory system, and hence limits both maximum metabolic rate and aerobic scope. Measurements of metabolic rate and fH were taken over a range of temperatures at rest and following exhaustive exercise in juvenile coho salmon (O. kisutch) to confirm the association between Topt and maximum fH. In vivo measurements revealed a maximum fH limitation at the Topt for aerobic scope, supporting the use of fH to estimate Topt. The potential for expediting measurements of maximum fH during acute warming was investigated using anaesthetized coho salmon and pharmacological stimulation of fH. In coho salmon sedated with low doses of anaesthetic, pharmacologically stimulated fH was equivalent to the maximum fH measured in vivo. Breakpoint analysis of the relationship between maximum fH and temperature demonstrated a limitation on maximum fH that corresponded closely with the Topt for aerobic scope. Further, while Topt measurements took three weeks to complete, maximum fH measurements were completed in three days. Therefore, the novel maximum fH technique considerably reduced the time needed to estimate Topt and may be broadly suited to estimating Topt both within and outside of the Oncorhynchus genus. Potential application of this rapid Topt estimation method is discussed in relation to temperature data collected from two local coho salmon-bearing streams. Temperature data also allowed for the examination of stream warming and cooling dynamics and identification of habitat critical to buffering anthropogenic disturbances to stream temperature. These data highlight the importance of riparian areas for maintaining the thermal integrity of waterways.

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Anoxic Survival and cardiovascular responses of the pacific hagfish (2010)

No abstract available.

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