The origins of apicomplexan sequence innovation.

The Apicomplexa are a group of phylogenetically related parasitic protists that include Plasmodium, Cryptosporidium, and Toxoplasma. Together they are a major global burden on human health and economics. To meet this challenge, several international consortia have generated vast amounts of sequence data for many of these parasites. Here, we exploit these data to perform a systematic analysis of protein family and domain incidence across the phylum. A total of 87,736 protein sequences were collected from 15 apicomplexan species. These were compared with three protein databases, including the partial genome database, PartiGeneDB, which increases the breadth of taxonomic coverage. From these searches we constructed taxonomic profiles that reveal the extent of apicomplexan sequence diversity. Sequences without a significant match outside the phylum were denoted as apicomplexan specialized. These were collated into 9134 discrete protein families and placed in the context of the apicomplexan phylogeny, identifying the putative origin of each family. Most apicomplexan families were associated with an individual genus or species. Interestingly, many genera-specific innovations were associated with specialized host cell invasion and/or parasite survival processes. Contrastingly, those families reflecting more ancestral relationships were enriched in generalized housekeeping functions such as translation and transcription, which have diverged within the apicomplexan lineage. Protein domain searches revealed 192 domains not previously reported in apicomplexans together with a number of novel domain combinations. We highlight domains that may be important to parasite survival.

The global landscape of sequence diversity.

BACKGROUND: Systematic comparisons between genomic sequence datasets have revealed a wide spectrum of sequence specificity from sequences that are highly conserved to those that are specific to individual species. Due to the limited number of fully sequenced eukaryotic genomes, analyses of this spectrum have largely focused on prokaryotes. Combining existing genomic datasets with the partial genomes of 193 eukaryotes derived from collections of expressed sequence tags, we performed a quantitative analysis of the sequence specificity spectrum to provide a global view of the origins and extent of sequence diversity across the three domains of life. RESULTS: Comparisons with prokaryotic datasets reveal a greater genetic diversity within eukaryotes that may be related to differences in modes of genetic inheritance. Mapping this diversity within a phylogenetic framework revealed that the majority of sequences are either highly conserved or specific to the species or taxon from which they derive. Between these two extremes, several evolutionary landmarks consisting of large numbers of sequences conserved within specific taxonomic groups were identified. For example, 8% of sequences derived from metazoan species are specific and conserved within the metazoan lineage. Many of these sequences likely mediate metazoan specific functions, such as cell-cell communication and differentiation. CONCLUSION: Through the use of partial genome datasets, this study provides a unique perspective of sequence conservation across the three domains of life. The provision of taxon restricted sequences should prove valuable for future computational and biochemical analyses aimed at understanding evolutionary and functional relationships.

Interaction network containing conserved and essential protein complexes in Escherichia coli.

Proteins often function as components of multi-subunit complexes. Despite its long history as a model organism, no large-scale analysis of protein complexes in Escherichia coli has yet been reported. To this end, we have targeted DNA cassettes into the E. coli chromosome to create carboxy-terminal, affinity-tagged alleles of 1,000 open reading frames (approximately 23% of the genome). A total of 857 proteins, including 198 of the most highly conserved, soluble non-ribosomal proteins essential in at least one bacterial species, were tagged successfully, whereas 648 could be purified to homogeneity and their interacting protein partners identified by mass spectrometry. An interaction network of protein complexes involved in diverse biological processes was uncovered and validated by sequential rounds of tagging and purification. This network includes many new interactions as well as interactions predicted based solely on genomic inference or limited phenotypic data. This study provides insight into the function of previously uncharacterized bacterial proteins and the overall topology of a microbial interaction network, the core components of which are broadly conserved across Prokaryota.

Beyond 100 genomes.

By the end of 2002, we witnessed the landmark submission of the 100th complete genome sequence in the databases. An overview of these genomes reveals certain interesting trends and provides valuable insights into possible future developments.

The phylogenetic extent of metabolic enzymes and pathways.

The evolution of metabolic enzymes and pathways has been a subject of intense study for more than half a century. Yet, so far, previous studies have focused on a small number of enzyme families or biochemical pathways. Here, we examine the phylogenetic distribution of the full-known metabolic complement of Escherichia coli, using sequence comparison against taxa-specific databases. Half of the metabolic enzymes have homologs in all domains of life, representing families involved in some of the most fundamental cellular processes. We thus show for the first time and in a comprehensive way that metabolism is conserved at the enzyme level. In addition, our analysis suggests that despite the sequence conservation and the extensive phylogenetic distribution of metabolic enzymes, their groupings into biochemical pathways are much more variable than previously thought.