Selection on Synthesis Cost Affects Interprotein Amino Acid Usage in All Three Domains of Life

Abstract

Most investigations of the forces shaping protein evolution have focused on protein function. However, cells are typically 50%-75% protein by dry weight, with protein expression levels distributed over five orders of magnitude. Cells may, therefore, be under considerable selection pressure to incorporate amino acids that are cheap to synthesize into proteins that are highly expressed. Such selection pressure has been demonstrated to alter amino acid usage in a few organisms, but whether "cost selection" is a general phenomenon remains unknown. One reason for this is that reliable protein expression level data is not available for most organisms. Accordingly, I have developed a new method for detecting cost selection. This method depends solely on interprotein gradients in amino acid usage. Applying it to an analysis of 43 whole genomes from all three domains of life, I show that selection on the synthesis cost of amino acids is a pervasive force in shaping the composition of proteins. Moreover, some amino acids have different price tags for different organisms--the cost of amino acids is changed for organisms living in hydrothermal vents compared with those living at the sea surface or for organisms that have difficulty acquiring elements such as nitrogen compared with those that do not--so I also investigated whether differences between organisms in amino acid usage might reflect differences in synthesis or acquisition costs. The results suggest that organisms evolve to alter amino acid usage in response to environmental conditions.

Metabolic and Translational Efficiency in Microbial Organisms

“…3; Table 5). This phenomenon of similar usage of synthesized and acquired amino acids has been observed indirectly before (Swire 2007), and is here shown directly. In order to confirm the validity of including exogenously acquired amino acids, analysis was performed without them.…”

“…Additionally, Seligmann utilized a simple count of synonymous codons across each whole genome to determine preference rather than determining usage in a subset of highly expressed genes. Swire (2007) examined 31 microbial organisms (as well as 12 Eukaryotes) but used the same costs for all organisms (those of E. coli). Swire's analysis avoided the use of a proxy for expressivity by focusing instead upon the consistent usage of amino acids with respect to protein cost (i.e., biosynthetically inexpensive proteins consistently utilize biosynthetically inexpensive amino acids).…”

Histidine Biosynthesis

“…The recent identification of the HISN7 enzyme in Arabidopsis, which catalyses the dephosphorylation of histidinol-P to histidinol (Petersen et al, 2010), has suggested the existence of additional potential links between His biosynthesis and other plant metabolic pathways. The recombinant HISN7 protein is able to catalyze the dephosphorylation of D-inositol-1(or 3)-P and L-galactose-1-P in vitro (Torabinejad et al, 2009) (after the aromatic amino acids Phe, Trp and Tyr), with estimates of 31-41 ATP molecules required per molecule of His produced (Alifano et al, 1996;Akashi and Gojobori, 2002;Swire, 2007). This may account for the relatively low abundance of His in proteins (where it is typically the 3rd or 4th least abundant amino acid) in line with the predictions of the cost minimization hypothesis, which seeks to explain the negative correlation between the frequency of amino acid usage and their biosynthetic cost (Seligmann, 2003).…”

Structural Studies of Medicago truncatula Histidinol Phosphate Phosphatase from Inositol Monophosphatase Superfamily Reveal Details of Penultimate Step of Histidine Biosynthesis in Plants

“…His is also one of the least abundant amino acids in proteins, probably because its biosynthesis is metabolically expensive (6), with 31-41 ATP molecules required to produce a single His molecule (7)(8)(9). Plants biosynthesize His similarly to prokaryotes (10).…”