Energy efficiency trade-offs drive nucleotide usage in transcribed regions.
Efficient nutrient usage is a trait under universal selection. A substantial part of cellular resources is spent on making nucleotides. We thus expect preferential use of cheaper nucleotides especially in transcribed sequences, which are often amplified thousand-fold compared with genomic sequences. To test this hypothesis, we derive a mutation-selection-drift equilibrium model for nucleotide skews (strand-specific usage of 'A' versus 'T' and 'G' versus 'C'), which explains nucleotide skews across 1,550 prokaryotic genomes as a consequence of selection on efficient resource usage. Transcription-related selection generally favours the cheaper nucleotides 'U' and 'C' at synonymous sites. However, the information encoded in mRNA is further amplified through translation. Due to unexpected trade-offs in the codon table, cheaper nucleotides encode on average energetically more expensive amino acids. These trade-offs apply to both strand-specific nucleotide usage and GC content, causing a universal bias towards the more expensive nucleotides 'A' and 'G' at non-synonymous coding sites.
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.|Structural and Computational Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany.
Wei-Hua
http://orcid.org/0000-0001-5160-4398
WH
Chen
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
Guanting
G
Lu
Structural and Computational Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany.|Bioinformatics department, Max Delbrück Centre for Molecular Medicine, Berlin 13125, Germany.
Peer
P
Bork
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
Songnian
http://orcid.org/0000-0003-3966-3111
S
Hu
Institute for Computer Science and Cluster of Excellence on Plant Sciences, Heinrich Heine University, Düsseldorf 40225, Germany.
Martin J
MJ
Lercher
D000596:Amino Acids / Q000235:genetics*; D001419:Bacteria / Q000235:genetics*; D001482:Base Composition; D020029:Base Pairing; D005075:Biological Evolution; D003062:Codon; D016680:Genome, Bacterial; D008957:Models, Genetic; D009154:Mutation; D009711:Nucleotides / Q000235:genetics*; D009876:Operon; D014176:Protein Biosynthesis; D012641:Selection, Genetic; D013816:Thermodynamics; D014158:Transcription, Genetic
D000596:Amino Acids; D003062:Codon; D009711:Nucleotides