Domestication and growth hormone transgenesis cause similar changes in gene expression in coho salmon (Oncorhynchus kisutch)

Abstract

Domestication has been extensively used in agricultural animals to modify phenotypes such as growth rate. More recently, transgenesis of growth factor genes [primarily growth hormone (GH)] has also been explored as a rapid approach to accelerating performance of agricultural species. Growth rates of many fishes respond dramatically to GH gene transgenesis, whereas genetic engineering of domestic mammalian livestock has resulted in relatively modest gains. The most dramatic effects of GH transgenesis in fish have been seen in relatively wild strains that have undergone little or no selection for enhanced growth, whereas genetic modification of livestock necessarily has been performed in highly domesticated strains that already possess very rapid growth. Such fast-growing domesticates may be refractory to further stimulation if the same regulatory pathways are being exploited by both genetic approaches. By directly comparing gene expression in wild-type, domestic, and GH transgenic strains of coho salmon, we have found that domestication and GH transgenesis are modifying similar genetic pathways. Genes in many different physiological pathways show modified expression in domestic and GH transgenic strains relative to wild-type, but effects are strongly correlated. Genes specifically involved in growth regulation (IGF1, GHR, IGF-II, THR) are also concordantly regulated in domestic and transgenic fish, and both strains show elevated levels of circulating IGF1. Muscle expression of GH in nontransgenic strains was found to be elevated in domesticated fish relative to wild type, providing a possible mechanism for growth enhancement. These data have implications for genetic improvement of existing domesticated species and risk assessment and regulation of emerging transgenic strains.

Fig. 1.

Growth rates and hormone profiles of wild-type (W), domesticated (D), and GH transgenic (T) salmon. (A) Specific growth rates (SGR). (B) Plasma IGF1 levels. n = 10 per genotype. Letters above bars denote significant differences among groups (1-way ANOVA, P < 0.05). Error bars represent standard SEM.

Fig. 2.

Spearman rank order correlations between domesticated/wild type gene expression ratio vs. transgenic/wild type gene expression ratio. (A) muscle. n = 456; r = 0.555; P < 0.001. (B) liver. n = 321; r = 0.640; P < 0.001. Genes with identical IDs but different Accession numbers (Table S1 and Table S2) were counted only once, and gene expression ratios averaged (Table S3, Table S4, Table S5, Table S6, Table S7, Table S8, Tables S9, and Table S10) for correlations. Linear (log₁₀–log₁₀) regression lines are shown.

Fig. 3.

Comparison of genes affected by domestication and GH transgenesis among different functional pathways. (A) muscle. (B) liver. Blue bars represent genes showing concordant responses in expression between domesticated and GH transgenic salmon. Red bars represent discordant responses.

Fig. 4.

Levels of mRNA for specific growth-related and control genes in muscle (A) and liver (B). Letters above bars represent statistical significance among groups with a single gene (1-way ANOVA, P < 0.05). See Table S11 for gene abbreviations. Error bars represent SEM