title: Global Shifts in Genome and Proteome Composition Are Very Tightly Coupled.
abstract: The amino acid composition (AAC) of proteomes differs greatly between microorganisms and is associated with the environmental niche they inhabit, suggesting that these changes may be adaptive. Similarly, the oligonucleotide composition of genomes varies and may confer advantages at the DNA/RNA level. These influences overlap in protein-coding sequences, making it difficult to gauge their relative contributions. We disentangle these effects by systematically evaluating the correspondence between intergenic nucleotide composition, where protein-level selection is absent, the AAC, and ecological parameters of 909 prokaryotes. We find that G + C content, the most frequently used measure of genomic composition, cannot capture diversity in AAC and across ecological contexts. However, di-/trinucleotide composition in intergenic DNA predicts amino acid frequencies of proteomes to the point where very little cross-species variability remains unexplained (91% of variance accounted for). Qualitatively similar results were obtained for 49 fungal genomes, where 80% of the variability in AAC could be explained by the composition of introns and intergenic regions. Upon factoring out oligonucleotide composition and phylogenetic inertia, the residual AAC is poorly predictive of the microbes' ecological preferences, in stark contrast with the original AAC. Moreover, highly expressed genes do not exhibit more prominent environment-related AAC signatures than lowly expressed genes, despite contributing more to the effective proteome. Thus, evolutionary shifts in overall AAC appear to occur almost exclusively through factors shaping the global oligonucleotide content of the genome. We discuss these results in light of contravening evidence from biophysical data and further reading frame-specific analyses that suggest that adaptation takes place at the protein level.
authors.affiliation: Division of Electronics, Rudjer Boskovic Institute, Zagreb, Croatia Molecular Basis of Ageing, Mediterranean Institute for Life Sciences (MedILS), Split, Croatia.
authors.forename: Maria
authors.initials: M
authors.lastname: Brbić
authors.affiliation: MRC Clinical Sciences Centre, Imperial College, Hammersmith Campus, London, United Kingdom.
authors.forename: Tobias
authors.initials: T
authors.lastname: Warnecke
authors.affiliation: Molecular Basis of Ageing, Mediterranean Institute for Life Sciences (MedILS), Split, Croatia.
authors.forename: Anita
authors.initials: A
authors.lastname: Kriško
authors.affiliation: Division of Electronics, Rudjer Boskovic Institute, Zagreb, Croatia EMBL/CRG Systems Biology Unit, Centre for Genomic Regulation, Barcelona, Spain fran.supek@irb.hr.
authors.forename: Fran
authors.initials: F
authors.lastname: Supek
mesh_terms: D000596:Amino Acids / Q000032:analysis; D001482:Base Composition; D021901:DNA, Intergenic / Q000737:chemistry; D016681:Genome, Fungal; D064349:Genome, Microbial; D023281:Genomics; D009711:Nucleotides / Q000032:analysis; D009841:Oligonucleotides / Q000032:analysis; D010802:Phylogeny; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000737:chemistry*; D016364:Reading Frames
chemical_list: D000596:Amino Acids; D021901:DNA, Intergenic; D009711:Nucleotides; D009841:Oligonucleotides; D011506:Proteins; D020543:Proteome
keywords: amino acid composition; ecological preferences; fungal genome; intergenic DNA; oligonucleotide composition; prokaryotic genome; support vector regression