Amino Acid Biosynthetic Cost and Protein Conservation

Abstract

Protein products of highly expressed genes tend to favor amino acids that have lower average biosynthetic costs (i.e., they exhibit metabolic efficiency). While this trend has been observed in several studies, the specific sites where cost-reducing substitutions accumulate have not been well characterized. Toward that end, weighted costs in conserved and variable positions were evaluated across a total of 9,119 homologous proteins in four mammalian orders (primate, carnivore, rodent, and artiodactyls), which together contain a total of 20,457,072 amino acids. Degree of conservation at homologous positions in these mammalian proteins and average-weighted cost across all positions within a single protein are significantly correlated. Dividing human genes into two classes (those with and those without CpG islands in their promoters) suggests that humans also preferentially utilize less costly amino acids in highly expressed genes. In contrast to the intuitive expectation that the relatively weak selective force associated with metabolic efficiency would be a selection pressure in complex multicellular organisms, the overall level of selective constraint within the variable regions of mammalian proteins allows the metabolic efficiency to derive a reduction of overall biosynthetic cost, particularly in genes with the highest levels of expression.

Evolution of Nucleotide Punctuation Marks: From Structural to Linear Signals

“…Hence avoidance of metabolic costs (Akashi and Gojobori, 2002; Seligmann, 2003, 2012b; Brocchieri and Karlin, 2005; Warringer and Blomberg, 2006; Heizer et al, 2011; Chen and Bundschuh, 2012; Raiford et al, 2012; Krick et al, 2014; Chen W.-H. et al, 2016) should favor evolution of linear consensus signals. Consequently, linear signals presumably evolved more recently to become punctuation marks with higher accuracy, specialization, and metabolic efficiency than structural signals.…”

Protein analysis of the spermatophore reveals diverse compositions in both the ampulla and the spermatophylax in a bushcricket

“…Furthermore, the diversification and size distribution of proteins in the spermatophylax is higher than expected, indicating that functions other than just structural integrity and the provision of a ‘cheap meal’ are involved. Even if protein diversity in the bushcricket spermatophylax is more a consequence of post‐translational modifications rather than genomic diversity, this weakens support for the ‘cheap spermatophylax hypothesis’ because post‐translational modifications also require significant metabolic energy investment (Seligmann, ; Heizer et al ., ).…”

“…The ‘cost minimization principle’ suggests that species minimize the cost of protein biosynthesis (Seligmann, ; Heizer et al ., ). Three aspects can be predicted to make proteins costly.…”

“…In crickets, glycine is known to affect the gustatory response of the females, keeping them occupied with feeding, leading to the formulation of the ‘Candymaker hypothesis’ for the spermatophylax (Warwick et al ., ). Glycine is not only the smallest, but also one of the cheapest amino acids to produce (Akashi & Gojobori, ; Wagner, ; Heizer et al ., ), making its use a cost effective way of enticing females to feed on the spermatophylax and detering them from premature removal of the sperm containing ampulla.…”

Metabolic and Translational Efficiency in Microbial Organisms

“…Detection of the subtle trends of biosynthetic cost selection driven changes often requires whole proteome analysis. The effects tend to accumulate in regions of proteins that are least functionally constrained (Heizer et al 2011), and the benefits are greatest in genes that are highly expressed. Secreted genes also undergo observable biosynthetic cost selection to minimize the loss of cellular resources (Smith 2010).…”