Essential amino acid usage and evolutionary nutrigenomics of eukaryotes - insights into the differential usage of amino acids in protein domains and extra-domains

Abstract

ABSTRACT. Nutrigenomics studies the effects of nutrients on the genome, transcriptome and proteome of organisms, and here an evolutionary standpoint on this new discipline is presented. It is well known that metazoan organisms are unable to synthesize all amino acids necessary to produce their proteins and that these essential amino acids (EAA) must be acquired from the diet. Here, we tested the hypothesis that conserved regions such as protein domains (DM) have different essentiality indexes and use different sets of amino acids when compared to extra-domains (ED) and proteins without mapped domains (WD). We found that auxotrophic organisms have a tendency to use less EAAs in DM than do prototrophic ones. Looking into the amino acid usage of eukaryotic proteins downloaded from KEGG and COG, we showed that WD have a usage of amino acids closer to DM, which suggests that proteins without mapped domains behave as large domains. Using an ED index that shows the proportion of prevalent amino acids in ED, a differential usage of amino acids in domains versus extra-domains was demonstrated. Protein domains were shown to be enriched with a higher number of EAA, and it may be related to the fact that these amino acids had lost their biosynthetic pathways in metazo- ans during a great amino acid pathway deletion, followed by a nutritional constraint that may have happened close to the conquest of the terrestrial environment. Thus, the proportion of EAA outside domains could have decreased during evolution due to nutritional constraints.

Amino acids biosynthesis and nitrogen assimilation pathways: a great genomic deletion during eukaryotes evolution

“…In previous work we hypothesized that a great event of genome deletion on which many of the intermediate enzymes for biosynthetic pathways for amino acids have vanished, ended up affecting the usage of EAAs in chordate proteomes [18,19]. In 2006, Payne and Loomis [10] using pFam protein signatures reported that protists and animals share essentiality for the nine amino acids.…”

Long-term melatonin treatment attenuates body weight gain with aging in female mice

“…3B) (Akram 2014), it is speculated that the downregulation of NEAAs by melatonin treatment was due to the downregulation of the metabolites in the TCA cycle, possibly due to the inhibition of glucose utilization. In contrast to NEAAs, EAAs are not synthesized in the body but are absorbed from diet (Santana-Santos et al 2008). Therefore, the downregulation of EAAs suggests that melatonin treatment inhibited the absorption of amino acids.…”

“…In our study, melatonin treatment decreased the level of not only NEAAs but also EAAs. Because EAAs are not synthesized in the body and are absorbed from the diet (Santana-Santos et al 2008), the melatonin-induced decrease in the levels of EAAs suggests that melatonin treatment attenuated the absorption of amino acids. In addition, melatonin treatment downregulated glucose-related metabolites, suggesting that melatonin attenuated glucose uptake.…”

Metazoan Remaining Genes for Essential Amino Acid Biosynthesis: Sequence Conservation and Evolutionary Analyses

“…In other extreme cases, such as in the metazoan EAA pathways, we suggest that this relaxation may lead to a pseudogenization cascade that might result in the deletion of each and every gene participating in a given pathway. However, when performing the evolutionary analysis of EAA biosynthetic pathways [ 2 , 8 , 9 ] in animals, our group found that some genes from these pathways are still present in metazoan genomes. In this manuscript, we analyze the sequence conservation and evolutionary fate of those metazoan REmaining GENes (ReGens).…”