Molecular Characterization and Functional Regulation of Melanocortin 2 Receptor (MC2R) in the Sea Bass. A Putative Role in the Adaptation to Stress

As African indigenous cattle evolved in a hot tropical climate, they have developed an inherent thermotolerance; survival mechanisms include a light-colored and shiny coat, increased sweating, and cellular and molecular mechanisms to cope with high environmental temperature. Here, we report the positive selection signature of genes in African cattle breeds which contribute for their heat tolerance mechanisms. We compared the genomes of five indigenous African cattle breeds with the genomes of four commercial cattle breeds using cross-population composite likelihood ratio (XP-CLR) and cross-population extended haplotype homozygosity (XP-EHH) statistical methods. We identified 296 (XP-EHH) and 327 (XP-CLR) positively selected genes. Gene ontology analysis resulted in 41 biological process terms and six Kyoto Encyclopedia of Genes and Genomes pathways. Several genes and pathways were found to be involved in oxidative stress response, osmotic stress response, heat shock response, hair and skin properties, sweat gland development and sweating, feed intake and metabolism, and reproduction functions. The genes and pathways identified directly or indirectly contribute to the superior heat tolerance mechanisms in African cattle populations. The result will improve our understanding of the biological mechanisms of heat tolerance in African cattle breeds and opens an avenue for further study.

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“…; Agulleiro et al . ). ESR2 belongs to the nuclear receptor family of transcription factors involved in the regulation of spermatogenesis.…”

Section: Resultsmentioning

confidence: 97%

Whole genome detection of signature of positive selection in African cattle reveals selection for thermotolerance

Taye

Lee

Caetano-Anollés

et al. 2017

Animal Science Journal

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“…mc2r is a member of melanocortin receptor family, expressed in interrenal cells at high levels and detectable in adipose tissue . mc2r gene products specifically bind to ACTH while other melanocortin receptor members (eg, mc1r, mc3r ‐ mc5r ) bind to melanocyte stimulating hormone as well as ACTH . mc2r initiates corticosteroid synthesis by increasing cyclic adenosine monophosphate (cAMP) levels, which in turn increases free cholesterol levels available for mitochondrial transport where corticosteroid synthesis occurs .…”

Section: Discussionmentioning

confidence: 99%

“…mc2r has two exons and only exon 2 is protein coding. The Mc2r protein is a trans‐membrane protein with only one known transcript and translational isoform . In contrast, NR3C1 in humans has eight translated exons (exon 2 through 9) and nine untranslated alternative first exons, each with a different promoter.…”

Section: Discussionmentioning

confidence: 99%

Novel zebrafish behavioral assay to identify modifiers of the rapid, nongenomic stress response

Lee

Schwab

Sigafoos

et al. 2019

Genes Brain and Behavior

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When vertebrates face acute stressors, their bodies rapidly undergo a repertoire of physiological and behavioral adaptations, which is termed the stress response. Rapid changes in heart rate and blood glucose levels occur via the interaction of glucocorticoids and their cognate receptors following hypothalamic‐pituitary‐adrenal axis activation. These physiological changes are observed within minutes of encountering a stressor and the rapid time domain rules out genomic responses that require gene expression changes. Although behavioral changes corresponding to physiological changes are commonly observed, it is not clearly understood to what extent hypothalamic‐pituitary‐adrenal axis activation dictates adaptive behavior. We hypothesized that rapid locomotor response to acute stressors in zebrafish requires hypothalamic‐pituitary‐interrenal (HPI) axis activation. In teleost fish, interrenal cells are functionally homologous to the adrenocortical layer. We derived eight frameshift mutants in genes involved in HPI axis function: two mutants in exon 2 of mc2r (adrenocorticotropic hormone receptor), five in exon 2 or 5 of nr3c1 (glucocorticoid receptor [GR]) and two in exon 2 of nr3c2 (mineralocorticoid receptor [MR]). Exposing larval zebrafish to mild environmental stressors, acute changes in salinity or light illumination, results in a rapid locomotor response. We show that this locomotor response requires a functioning HPI axis via the action of mc2r and the canonical GR encoded by nr3c1 gene, but not MR ( nr3c2 ). Our rapid behavioral assay paradigm based on HPI axis biology can be used to screen for genetic and environmental modifiers of the hypothalamic‐pituitary‐adrenal axis and to investigate the effects of corticosteroids and their cognate receptor interactions on behavior.

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“…whereas the reference genes eukaryotic elongation factor 1 ( elf1a ) and ribosomal 18S RNA ( 18S ) were used as in previous work41. Primer design for melanocortin 1 receptor ( mc1r ), melanocortin 2 receptor ( mc2r ) and pro-opiomelanocortin ( pomc ) was based on the available sequences with accession numbers FN377856.142, FR870225.114, and AY691808.14. The forward primer for mc1r has the sequence 5′ CTCCACCTCATCCTCATC 3′ while the reverse 5′ GAAGCACCAAGAACACAG 3′.…”

Section: Methodsmentioning

confidence: 99%

“…Relatively few studies have focused on the function and characterization of MC2R in fish910111213 and a recent study conducted in European sea bass demonstrated a negative feedback by cortisol on MC2R expression in a chronic stress paradigm14.…”

mentioning

confidence: 99%

α-MSH and melanocortin receptors at early ontogeny in European sea bass (Dicentrarchus labrax, L.)

Tsalafouta

Gorissen

Pelgrim

et al. 2017

Sci Rep

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Temporal patterns of whole-body α-MSH concentrations and of transcripts of melanocortin receptors during early development as well as the endocrine response (α-MSH, cortisol, MCR mRNAs) to stress at the end of the larval period were characterized in Dicentrarchus labrax. Immunohistochemistry showed α-MSH positive cells in the pituitary pars intermedia in all stages examined. As development proceeds, α-MSH content gradually increases; mRNA levels of mc2r and mc4r remain low until first feeding where peak values are observed. Mc1r expression was constant during development, pomc mRNA levels remain low until the stage of flexion after which a significant increase is observed. At the stage of the formation of all fins, whole-body cortisol and α-MSH concentrations responded with peak values at 2 h post stress. Additionally, the stress challenge resulted in elevated transcript levels of pomc, mc2r and mc4r but not in mc1r, with a pattern characterized by peak values at 1 h post stress and a strong correlation with whole body α-MSH concentrations was found. Our data provide for the first time a view on the importance of the α-MSH stress response in early development of European sea bass, an additional and relatively poorly understood signal involved in the stress response in teleosts.

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Molecular Characterization and Functional Regulation of Melanocortin 2 Receptor (MC2R) in the Sea Bass. A Putative Role in the Adaptation to Stress

Cited by 40 publications

References 45 publications

Whole genome detection of signature of positive selection in African cattle reveals selection for thermotolerance

Whole genome detection of signature of positive selection in African cattle reveals selection for thermotolerance

Novel zebrafish behavioral assay to identify modifiers of the rapid, nongenomic stress response

α-MSH and melanocortin receptors at early ontogeny in European sea bass (Dicentrarchus labrax, L.)

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