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. 2018 Dec 18;24(1):175–194. doi: 10.1007/s12192-018-0954-6

Table 4.

Analysis of groups of physiological pathways comparing Ethiopian highland and lowland chicken at three different time points during the day under the lowland environmental conditions: in the morning, at noon, and in the evening of heart (A), (breast) muscle (B), and spleen (C) tissues

A. Heart
Animal groups Major pathways–groups of pathways
Highland vs. lowland—all time points ATP synthesis coupled transport; coenzyme biosynthetic process; cellular carbohydrate catabolic process–positive regulation of B cell activation; positive regulation of proteasomal protein catabolic process–cGMP-PKG signaling pathway–negative regulation of muscle contraction; negative regulation of muscle hypertrophy; myoblast differentiation–regulation of phospholipase C activity; cognition–Rap1 signaling; B cell receptor signaling pathway; chronic myeloid leukemia; cytokine production involved in immune response/regulation of fat cell differentiation; positive regulation of fat cell differentiation; asymmetric cell division/inner ear receptor cell development; establishment of planar polarity/DNA strand elongation/neutral lipid process; glycerolipid metabolism/microtubule-based movement; cilium movement/sulfur amino acid metabolic process/glycosphigolipid metabolic process/collagen fibril organization/mitochondrial translation initiation/lipid storage/negative regulation of transmembrane transport/Rho GTPase cycle/regulation of RNA stability/negative regulation of G protein-coupled receptor protein signaling pathway
 Morning Associative learning/sister chromatid cohesion/epithelium cilium movement involved in determination left-right asymmetry/cardiac muscle cell development
 Noon Toll-like receptor TLR1-TLR2 signaling pathway; lymphocyte homeostasis; positive regulation of lipid metabolic process/regulation of membrane repolarization/positive regulation of cAMP biosynthetic process/heart looping/cell cycle DNA replication/trans-Golgi network vesicle budding/protein targeting to vacuole/GPI anchor biosynthetic process
 Evening Processing of capped intronless pre-mRNA/activation of matrix metalloproteinases/assembly of collagen fibrils and other multimeric structures/epithelial cell morphogenesis
Highland*—all time points mRNA catabolic process

 Morning–

noon

mRNA processing/nuclear transcribed mRNA catabolic process exonucleolytic; cell-cell junction organization; regulation of systemic arterial blood pressure; oxygen transport
 Noon–evening Response to auditory stimulus/regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains/RHO GTPases activate formins/regulation of potassium transport/regulation of transcription from RNA polymerase II promoter/lens morphogenesis in camera-type eye/adherens junction/cellular response to glucose starvation
 Morning–evening Unfolded protein response (UPR); RNA surveillance/cell-cell junction assembly/negative regulation of circadian rhythm
Lowland*—all time points Positive regulation of metabolic process; positive regulation of molecular function; protein modification process/organelle organization/cell cycle
 Morning–noon Coenzyme biosynthetic process/arachidonic acid metabolism/mesonephric tubule morphogenesis/regulation of phospholipase C activity/cellular component disassembly involved in execution phase of apoptosis
 Noon–evening* Regulation of early endosome to recycling endosome transport/3′-UTR-mediated mRNA destabilization/coenzyme A catabolic process/optic placode formation involved in camera-type eye formation/amniotic stem cell differentiation/vagus nerve morphogenesis/l-ascorbic acid biosynthetic process/negative regulation of cellular amino acid metabolic processes/signal transduction involved in intra-S DNA damage checkpoint/nuclear mRNA surveillance of mRNA 3′-end processing/negative regulation of interleukin-6-mediated signaling pathway
 Morning–evening* Regulation of interleukin-4 biosynthetic process; interleukin-4 biosynthetic process; primitive erythrocyte differentiation–negative regulation of histone H3-K4 methylation; negative regulation of centrosome duplication–skeletal muscle thin filament assembly/negative regulation of filopodium assembly/activation of meiosis involved in egg activation/regulation of DNA-templated transcription termination/3′-UTR-mediated mRNA destabilization/lateral mesoderm cell fate commitment/geranyl diphosphate metabolic process/coenzyme A catabolic process/positive regulation of sequestering of calcium ion/amniotic stem cell differentiation/regulation of protein tetramerization/coenzyme A transport/heme A biosynthetic process/negative regulation of uterine smooth muscle contraction/protein processing in phagocytic vesicle/positive regulation of protein deubiquitination/histone H3-K27 acetylation/membrane depolarization during AV node cell action potential/diadenosine polyphosphate metabolic process/transcription initiation from RNA polymerase I promoter large rRNA transcript
B. Muscle
Animal groups Major pathways–groups of pathways
Highland vs. lowland*—all time points Beta-alanine biosynthetic process; negative regulation of vascular endothelial growth factor signaling pathway/cell migration involved in metanephros development; medium chain fatty acid transport; phosphatidylserine biosynthetic process/regulation of centromeric sister chromatid cohesion/VEGF-activated neuropilin signaling pathway/regulation of membrane depolarization during cardiac muscle cell action potential/acetate metabolic process/regulation of sulfur amino acid metabolic process/regulation of telomere maintenance via semi-conservative replication/dipeptide membrane transport/activation of meiosis involved in egg activation/positive regulation of centrosome duplication/cervix development/glycosyl ceramide biosynthetic process/negative regulation of skeletal muscle cell differentiation/negative regulation of eosinophil activation/N-terminal protein palmitoylation/lysine import/coenzyme A transport/positive regulation of TRAIL production/Wnt signaling pathway involved in digestive tract morphogenesis/UDP-N-acetyl glucose transport/regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator/negative regulation of glucocorticoid-mediated signaling pathway/cytoplasmic translational elongation/elastin biosynthetic process/transcription initiation from RNA polymerase I promoter for nuclear large rRNA transcript
 Morning* Negative regulation of proteasome ubiquitin-dependent protein catabolic process/glycerophospholipid biosynthesis/cellular carbohydrate catabolic process/protein O-linked glycosylation
 Noon* Negative regulation of filopodium assembly/dipeptide transmembrane transport/cervix development/induction by symbiont of host defense response/endosome to lysosome transport via multivesicular body sorting pathway/regulation of microglial cell activation/regulation of protein import into mitochondrial outer membrane/coronary vein morphogenesis/negative regulation of nucleobase-containing compound transport/regulation of neutrophil apoptotic process/regulation of natural killer cell cytokine production/succinate transport
 Evening* Mitochondrial RNA 3′-end processing/limb joint morphogenesis/N-terminal amino acid methylation/reversal of alkylation damage by DNA dioxygenases/lysine import/coronary morphogenesis/positive regulation of TRAIL production/positive regulation of Schwann cell differentiation/atrial ventricular junction remodeling/TIRAP-dependent toll-like receptor signaling pathway/negative regulation of phosphatidylinositol biosynthetic process/regulation of intrinsic apoptotic signaling pathway response to osmotic stress by p53 class mediator/CVT pathway/negative regulation of glucocorticoid-mediated signaling pathway/elastin biosynthetic process/acetate biosynthetic process/transcription initiation from RNA polymerase I promoter for nuclear large rRNA transcript
Highland*—all time points Canonical Wnt signaling pathway involved in positive regulation of epithelial to mesenchymal transition/induction by symbiont of host defense response/regulation of DNA-templated transcription termination/mitochondrial RNA surveillance/.../vagus nerve morphogenesis
 Morning–noon Blood vessel endothelial cell migration; positive regulation of cellular carbohydrate metabolic process–signaling by NOTCH1; primary neural tube formation; hormone biosynthetic process; retinol metabolic process–protein deacetylation; alpha linolenic acid (ALA) metabolism/regulation of interleukin 12 biosynthetic process; interleukin 12 biosynthetic process/GABA synthesis, release, reuptake, and degradation/dolichol-linked oligosaccharide biosynthetic process/protein homotetramerization/DNA-templated transcription termination/histone H4 acetylation/IRE1-mediated unfolded protein response/termination of G protein-coupled receptor signaling pathway
 Noon–evening Positive regulation of viral transcription/proteasome maturation/regulation of stress fiber assembly/negative regulation of G protein-coupled receptor protein signaling pathway/vitamin transport/organophosphate ester transport/rRNA processing
 Morning–evening Retrograde neurotrophin signaling; DNA-templated transcription elongation; transcription elongation from RNA polymerase II promoter; Ca2+ pathway–regulation of epithelial cell differentiation–morphogenesis of embryonic epithelium–regulation of erythrocyte differentiation; positive regulation of peptide hormone secretion; unsaturated fatty acid biosynthetic process; PPAR signaling pathway–mitotic spindle organization; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; negative regulation of proteasomal protein catabolic process
Lowland*—all time points Positive regulation of branching involved in lung morphogenesis/negative regulation of sequestering of triglyceride/histone H3-K36 trimethylation/positive regulation of centrosome duplication/regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis/induction by symbiont of host defense response/regulation of DNA-templated transcription termination/marginal zone B cell differentiation/coronary vein morphogenesis/negative regulation of nucleobase-containing compound transport/regulation of neutrophil apoptotic process/cadmium ion homeostasis/Golgi to plasma membrane CFTR protein transport/l-ascorbic acid biosynthetic process/xanthine metabolic process/CVT pathway/negative regulation of phospholipase C activity/succinate transport/negative regulation of intestinal phytosterol absorption/transcription initiation from RNA polymerase I promoter for nuclear large rRNA transcript
 Morning–noon Photoperiodism; PPARA activates gene expression; glycerolipid metabolism/ribonucleoprotein complex biogenesis/regulation of double-strand break repair via homologous recombination/signal transduction involved in cell cycle checkpoint/eye morphogenesis/cellular response to mechanical stimulus/response to vitamin/transcription elongation from RNA polymerase I promoter/histone methylation/positive regulation of stress-activated MAPK cascade/recruitment of mitotic centrosome proteins and complexes/regulation of mRNA stability/positive regulation of leukocyte chemotaxis/pre-NOTCH expression and processing/cellular monovalent inorganic cation homeostasis
 Noon–evening Male gonad development; regulation of response to extracellular stimulus–blood vessel endothelial cell proliferation involved in sprouting angiogenesis–negative regulation of DNA biosynthetic process; positive regulation of stem cell proliferation; negative regulation of nuclear division (with muscle pathways!); neural tube patterning/positive regulation of axon extension/glycolysis + gluconeogenesis/SUMOylation of DNA damage response and repair proteins/response to ionizing radiation
 Morning–evening Glutamate receptor signaling pathway; oxytocin signaling pathway–adipocytokine signaling pathway–negative regulation of mononuclear cell proliferation; regulation of mesenchymal cell proliferation; mesenchymal cell proliferation–TGF-beta signaling pathway; embryonic digit morphogenesis; osteoblast proliferation–shigellosis/DNA-templated transcription termination; mRNA3′-end processing/response to ammonium ion/NRAGE signals death through JNK/glycerolipid metabolism/centrosome cycle/mitotic G1-G1S phases/regulation of plasma membrane organization
C. Spleen
Animal groups Major pathways–groups of pathways
Highland vs. lowland—all time points Detection of mechanical stimulus involved in sensory perception of sound; response to mechanical stimulus; neuroactive ligand-receptor interaction; associative learning–monovalent inorganic cation homeostasis; hormone biosynthetic process/lymphocyte homeostasis/response to acid chemical/entry into host cell/positive regulation of Rho protein signal transduction
 Morning Maintenance of protein location in cell; regulation of chromosomal segregation; anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; E2F-mediated regulation of DNA replication/protein processing in endoplasmic reticulum/regulation of fibroblast proliferation
 Noon Organelle biosynthesis and maintenance; chromosome segregation–anchoring of the basal body to the plasma membrane/negative regulation of protein localization to nucleus/trans-Golgi network vesicle budding/mitotic spindle organization/regulation of mRNA splicing, via spliceosome
 Evening ...Too small to mention any...
Highland*—all time points Regulation of glycolytic process by regulation of transcription from RNA polymerase II; regulation of platelet-derived growth factor receptor-alpha signaling pathway/interleukin 4 biosynthetic process/regulation of phosphatidylcholine biosynthetic process/maintenance of mitotic sister chromatid cohesion/positive regulation of ER to Golgi vesicle-mediated transport/protein localization to nonmotile primary cilium/tongue muscle cell differentiation/negative regulation of eosinophil activation/positive regulation of oocyte development/dosage compensation by inactivation of X chromosome/spermidiane catabolic process/positive regulation of aldosterone metabolism/mitochondrial mRNA catabolic process/regulation of protein import into mitochondrial outer membrane/positive regulation of chromatin silencing/cerebellar cortex structural organization/proline catabolism/protein localization to vacuolar membrane/synaptic vesicle uncoating/response to biotin/receptor-mediated virion attachment to host cell/dolichol metabolic process
 Morning–noon PI metabolism; phosphatidylinositol dephosphorylation–steroid hormone secretion; C21 steroid hormone biosynthetic process–regulation of receptor biosynthetic process–pre-NOTCH expression and processing; signaling by NOTCH–ARMS-mediated activation; Golgi cisternae pericentriolar stack reorganization; condensation of prometaphase chromosomes; nuclear envelope breakdown; M phase; mRNA transport; transcription organization from RNA polymerase III promoter; cytosolic sensors of pathogen-associated DNA; TRAF3-depedent IRF activation pathway; BBsome-mediated cargo-targeting to cilium; folding of actin by CCT/TriC; mitotic prometaphase (close to M phase); RHO GTPases activate formin; mitotic sister chromatic segregation; cell cycle; cell cycle checkpoints; regulation of spindle organization; histone monoubiquitination; histone H3 acetylation; peptidyl-lysine methylation; regulation of PLK1 activity at G2/M transition; regulation of protein phosphatase type 2A activity/anterograde axon cargo transport/thromboxane signaling through TP receptor/cochlea morphogenesis/methionine metabolic process/mitochondrial translation termination/cytoplasmic mRNA processing body assembly/COPII-coated vesicle budding/RNA destabilization/negative regulation of DNA recombination/protein K63-linked deubiquitination/C-protein coupled purinergic nucleotide receptor signaling pathway
 Noon–evening Interleukin 4 signaling; prolactin signaling pathway/NOTCH intracellular domain regulates transcription/protein localization to microtubule cytoskeleton/postreplication repair/trans-Golgi network vesicle budding/NLS-bearing protein import into nucleus/positive regulation of chromatin modification/cytoskeleton-dependent intracellular transport
 Morning–evening* SHC-related events triggered by IGF-1R; regulation of anoikis/nucleotide excision repair/regulation of water loss via skin; conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase; APC-Cdc20-mediated degradation of NEK2A/cerebral cortex neuron differentiation; regulation of phosphatidylcholine biosynthetic process/mitotic chromosome condensation/nucleotide-sugar metabolic process/protein export/transport of the SLBP-independent mature mRNA/terpenoid backbone biosynthesis/negative regulation of protein dephosphorylation/phospholipase C-activating dopamine receptor signaling pathway/positive regulation of RNA splicing/S-adenosylmethionine cycle/Huntington’s disease/CDP-diacylglycerol biosynthetic process/ER to Golgi vesicle-mediated transport/mitochondrial ATP synthesis coupled proton transport/CBP1(S) activates chaperone genes/SNARE complex assembly/mitotic prometaphase/regulation of hypoxia-inducible factor (HIF) by oxygen/aorta morphogenesis/centriole replication
Lowland*—all time points Negative regulation of osteoclast differentiation; copper ion homeostasis; microtubule cytoskeleton organization involved in mitosis; regulation of centriole elongation; heart formation; spermatic nucleus differentiation; autophagic vacuole assembly; CVT pathway–subpallium development; anterograde axon cargo transport; cochlea morphogenesis; DNA hypermethylation; positive regulation of transcription from RNA polymerase II promoter in response to stress; sphingolipid catabolic process–positive regulation of peptidyl-threonine phosphorylation; mitochondrial biosynthesis; pre-NOTCH expression and processing; retrograde transport, endosome to Golgi–FOXO signaling pathway; oocyte maturation/circadian regulation of translation/transcription from RNA polymerase I promoter/protein refolding/vitamin digestion and absorption/cellular response to heat stress; mitochondrial translation initiation/regulation of T helper 1 type immune response/regulation of fatty acid beta-oxidation/regulation of intracellular steroid hormone receptor signaling pathway/cholesterol biosynthesis/glycosylphosphatidylinositol (GPI)-anchor biosynthesis/energy coupled proton transmembrane transport, against electrochemical gradient/positive regulation of signal transduction by P53 class mediator/metabolism of porphyrins/SUMOyl DNA damage response and repair process/phosphatidylethanol metabolic process/negative regulation of insulin secretion/embryonic placenta morphogenesis/G protein-coupled purinergic receptor signaling pathway/positive regulation of receptor internalization/synaptic vesicle fusion to presynaptic membrane
 Morning–noon Interleukin-17 production; regulation of interleukin-17 production/mitotic metaphase plate congression/cholesterol biosynthesis/fructose and mannose metabolism/neutral lipid biosynthetic process
 Noon–evening Mitochondrial translation/nucleoside triphosphate biosynthetic process
 Morning–evening* Regulation of centrosome cycle; cytoplasmic microtubule organization; regulation of proteasomal ubiquitin-dependent protein catabolic process; PI3K events in ERBB3 signaling; PI3K events in ERBB4 signaling; antigen activates B cell receptor (BCR) leading to generation of second messengers; prostate cancer; negative regulation of cellular response to oxidative stress; Synthesis of PE–AKT phosphorylates targets in the nucleus; negative regulation of smooth muscle differentiation–organelle transport along microtubule/ER to Golgi vesicle-mediated transport/protein localization to kinetochore/regulation of intracellular steroid hormone receptor signaling pathway; GPI anchor metabolic process/mismatch repair/neural tube closure

All groups larger than two pathways are shown, with groups containing three pathways shown in bold. Please note that several datasets were too large to analyze due to large numbers of differentially expressed genes. To solve this, the software was set to maximum specificity, leading to less results. These analyses are marked with an asterisk