Structural genomics analysis: Characteristics of atypical, common, and horizontally transferred folds

Abstract

We conducted a structural genomics analysis of the folds and structural superfamilies in the first 20 completely sequenced genomes by focusing on the patterns of fold usage and trying to identify structural characteristics of typical and atypical folds. We assigned folds to sequences using PSI-blast, run with a systematic protocol to reduce the amount of computational overhead. On average, folds could be assigned to about a fourth of the ORFs in the genomes and about a fifth of the amino acids in the proteomes. More than 80% of all the folds in the SCOP structural classification were identified in one of the 20 organisms, with worm and E. coli having the largest number of distinct folds. Folds are particularly effective at comprehensively measuring levels of gene duplication, because they group together even very remote homologues. Using folds, we find the average level of duplication varies depending on the complexity of the organism, ranging from 2.4 in M. genitalium to 32 for the worm, values significantly higher than those observed based purely on sequence similarity. We rank the common folds in the 20 organisms, finding that the top three are the P-loop NTP hydrolase, the ferrodoxin fold, and the TIM-barrel, and discuss in detail the many factors that affect and bias these rankings. We also identify atypical folds that are "unique" to one of the organisms in our study and compare the characteristics of these folds with the most common ones. We find that common folds tend be more multifunctional and associated with more regular, "symmetrical" structures than the unique ones. In addition, many of the unique folds are associated with proteins involved in cell defense (e.g., toxins). We analyze specific patterns of fold occurrence in the genomes by associating some of them with instances of horizontal transfer and others with gene loss. In particular, we find three possible examples of transfer between archaea and bacteria and six between eukarya and bacteria. We make available our detailed results at http://genecensus.org/20.

An Evolutionarily Structured Universe of Protein Architecture

“…Out of 138,377 entries, an average of ‫5.1ע4.83‬ (SE) % (range 9.7%-48.6%) matched SCOP domains, and ‫8.0ע5.91‬ % (range 9.5%-28.3%) had enzymatic activities associated with them. For comparison purposes, we also used a data set that matched 420 fold categories in SCOP 1.39 and was generated by PSI-BLAST comparisons between PDB and genome sequence entries in the first 20 genomes ever to be sequenced (Hegyi et al 2002). We considered soluble proteins that grouped into major structural classes: all-␣ proteins with structures composed mostly of ␣-helices (␣), all-␤ proteins with mostly ␤-sheets (␤), ␣/␤ proteins with interspersed ␣-helices and ␤-sheets (␣/␤), ␣+␤ proteins containing segregated ␣-helices and ␤-sheet regions (␣+␤), multidomain proteins containing domains belonging to different classes and without known homologs (M), and small proteins (S).…”

“…Uniform distribution patterns are suggestive of common ancestry and longterm architectural stability, and are spread by vertical descent (Hegyi et al 2002). Uneven distribution patterns are suggestive of horizontal gene transfer (HGT), gene loss, convergence, and rapid divergence (Eisen 2000).…”

Automated structure prediction of weakly homologous proteins on a genomic scale

“…These threading assignment results are quite similar to that of the PDB benchmark, with a slightly larger portion of targets assigned to the easy set in E. coli, which may be due to the fact that homologues are not excluded. It should also be mentioned that genome scale structure predictions have been performed by many authors on different organisms (21)(22)(23)(24)(25)(26)(27). Most are based on homology modeling or sequence comparison techniques, which require solved homologous structures.…”

Universal Sharing Patterns in Proteomes and Evolution of Protein Fold Architecture and Life

“…Protein folds are among the most conserved components in nature, making them good candidates for the study of distant evolutionary relationships. Folds were surveyed in a number of genomes (Gerstein and Levitt 1997;Gerstein 1997Gerstein , 1998Frishman and Mewes 1997;Wolf et al 1999;Hegyi et al 2002) and indexed in several databases (Lee et al 2003). Fold composition, measured as presence-absence of individual folds, was used to reconstruct whole-genome trees based on the idea that closely related organisms must share significantly more fold architectures than distantly related ones (Gerstein 1998;Wolf et al 1999;Lin and Gerstein 2000).…”