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Natural selection seems to contribute to evolution after genotype alternations. In the codon table, Gly is encoded with GGT, GGC, GGA and GGG, and Glu is encoded with GAG and GAA, while Lys is encoded with AAA and AAG. These relationships indicate that high G and low A contents produce acidic proteins rather than basic proteins, because Gly is a neutral amino acid. Indeed, Glu content in fish cell hydrolysates was higher than that in rat or human cell hydrolysates [11]. In many fish that lack urea production in nitrogen metabolism, ammonia (which is fatally toxic to organisms) is excreted directly out of the body. Terrestrial vertebrates including mammals have a urea Bleomycin research buy cycle, and excrete urea as a final nitrogen metabolite. As acidic proteins contribute to neutralize ammonia in the bodies of fish, high G and low A content must be linked with aquatic Duvelisib order vertebrate evolution. In the dark-spotted frog (Rana nigromaculata) tadpoles are aquatic and ammonotelic, whereas after metamorphosis, the adult, which has a urea cycle, is terrestrial. This amphibian was grouped with aquatic vertebrates based on Ward��s clustering analysis using amino acid composition or nucleotide contents predicted from complete mitochondrial genomes as traits [25], and its G content was much closer to that of aquatic vertebrates in this study. Thus, these results seem to be based on genomic PRDX4 characteristics of R. nigromaculata. We have proposed that separation between aquatic and terrestrial vertebrates might be linked with nitrogen metabolism in biological evolution. ACKNOWLEDGEMENTS Declared none. CONFLICT OF INTEREST The authors confirm that this article content has no conflicts of interest. SUPPLEMENTARY MATERIAL Supplementary material is available on the publisher��s web site along with the published article. Click here to view.(813K, pdf)""Effective prevention and treatment strategies are urgently needed for pancreatic cancer, the 4th leading cause of cancer-related death in both men and women in the United States [1]. Less than 15% of pancreatic cancer patients have localized disease amenable to curative resection, and the overall 5-year survival rate in affected patients is less than 5% [2]. Obesity is an established pancreatic cancer risk and progression factor in humans and animal models [3-5]. In contrast, calorie restriction (CR) prevents or reverses obesity and related metabolic perturbations and pancreatic tumor development and/or progression in experimental models [6-11]; the impact of CR on human pancreatic cancer has not been well studied. CR results in a negative energy balance state and exerts its antitumor effects, at least in part, through decreased mammalian target of rapamycin (mTOR) signaling in many epithelial tissues [7-9,11,12].