Abstract
Essential amino acids (EAA) consist of a group of nine amino acids that animals are unable to synthesize via de novo pathways. Recently, it has been found that most metazoans lack the same set of enzymes responsible for the de novo EAA biosynthesis. Here we investigate the sequence conservation and evolution of all the metazoan remaining genes for EAA pathways. Initially, the set of all 49 enzymes responsible for the EAA de novo biosynthesis in yeast was retrieved. These enzymes were used as BLAST queries to search for similar sequences in a database containing 10 complete metazoan genomes. Eight enzymes typically attributed to EAA pathways were found to be ubiquitous in metazoan genomes, suggesting a conserved functional role. In this study, we address the question of how these genes evolved after losing their pathway partners. To do this, we compared metazoan genes with their fungal and plant orthologs. Using phylogenetic analysis with maximum likelihood, we found that acetolactate synthase (ALS) and betaine-homocysteine S-methyltransferase (BHMT) diverged from the expected Tree of Life (ToL) relationships. High sequence conservation in the paraphyletic group Plant-Fungi was identified for these two genes using a newly developed Python algorithm. Selective pressure analysis of ALS and BHMT protein sequences showed higher non-synonymous mutation ratios in comparisons between metazoans/fungi and metazoans/plants, supporting the hypothesis that these two genes have undergone non-ToL evolution in animals.
Highlights
It has been known for decades that most animal cells are incapable of growing in a medium lacking amino acid supplements [1]
This means that pathways for de novo amino acid biosynthesis are missing in their genomes, characterizing the Essential Amino Acid (EAA) phenotype
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
Summary
It has been known for decades that most animal cells are incapable of growing in a medium lacking amino acid supplements [1]. When organisms lose key enzymes in a pathway, genes encoding their upstream or downstream pathway partners should experience relaxation in the selection pressure Such relaxation has been observed in whole genome duplication events, since many gene copies turn out to be unnecessary [5,6,7]. 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). We study the sequence conservation of the whole set of ReGens, consisting of eight enzymes originally involved in the EAA biosynthetic pathways and shown to be present in the human and most animal genomes [2]
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