DOI: 10.5061/dryad.gk90t
title: Data from: Widespread position-specific conservation of synonymous rare codons within coding sequences

description: Synonymous rare codons are considered to be sub-optimal for gene
 expression because they are translated more slowly than common codons. Yet
 surprisingly, many protein coding sequences include large clusters of
 synonymous rare codons. Rare codons at the 5’ terminus of coding sequences
 have been shown to increase translational efficiency. Although a general
 functional role for synonymous rare codons farther within coding sequences
 has not yet been established, several recent reports have identified
 rare-to-common synonymous codon substitutions that impair folding of the
 encoded protein. Here we test the hypothesis that although the usage
 frequencies of synonymous codons change from organism to organism, codon
 rarity will be conserved at specific positions in a set of homologous
 coding sequences, for example to tune translation rate without altering a
 protein sequence. Such conservation of rarity–rather than specific codon
 identity–could coordinate co-translational folding of the encoded protein.
 We demonstrate that many rare codon cluster positions are indeed conserved
 within homologous coding sequences across diverse eukaryotic, bacterial,
 and archaeal species, suggesting they result from positive selection and
 have a functional role. Most conserved rare codon clusters occur within
 rather than between conserved protein domains, challenging the view that
 their primary function is to facilitate co-translational folding after
 synthesis of an autonomous structural unit. Instead, many conserved rare
 codon clusters separate smaller protein structural motifs within
 structural domains. These smaller motifs typically fold faster than an
 entire domain, on a time scale more consistent with translation rate
 modulation by synonymous codon usage. While proteins with conserved rare
 codon clusters are structurally and functionally diverse, they are
 enriched in functions associated with organism growth and development,
 suggesting an important role for synonymous codon usage in organism
 physiology. The identification of conserved rare codon clusters advances
 our understanding of distinct, functional roles for otherwise synonymous
 codons and enables experimental testing of the impact of synonymous codon
 usage on the production of functional proteins.
description: aln_ortho.tarAlignment data of orthologs (protein) in FASTA format, with induced gaps represented by a '-'lookup_tables.tarMapping of project short gene IDs to NCBI/Genbank accessions, including relevant annotation datault_mm.tarMin-max data for each aligned protein, one row per position of the alignment. This data went into the co-occurrence analysisminmax_pval_aln.tarMin max data with p-values per position, across the orthologs in alignment position spacegroupCATH.boundariesaligned position relative to CATH domains; format is: ortholog group, IN/OUT, position in domain, position in alignment. If a given position is not in a domain NA is placed in the domain positiongroupSCOP.boundariesaligned position relative to SCOP domains; format is: ortholog group, IN/OUT, position in domain, position in alignment. If a given position is not in a domain NA is placed in the domain positionsig_pruned_masked_p.05final set of significantly co-occurring codons with a p-value &lt;= 0.05 after pruning as described in the text