How do proteins gain new domains?
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ABSTRACT:
SUBMITTER: Marsh JA
PROVIDER: S-EPMC2926777 | biostudies-literature | 2010
REPOSITORIES: biostudies-literature
Publications
A study of the contributions of different mechanisms of domain gain in animal proteins suggests that gene fusion is likely to be most frequent. ...[more]
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Project description:BACKGROUND: Proteins are composed of a combination of discrete, well-defined, sequence domains, associated with specific functions that have arisen at different times during evolutionary history. The emergence of novel domains is related to protein functional diversification and adaptation. But currently little is known about how novel domains arise and how they subsequently evolve. RESULTS: To gain insights into the impact of recently emerged domains in protein evolution we have identified all human young protein domains that have emerged in approximately the past 550 million years. We have classified them into vertebrate-specific and mammalian-specific groups, and compared them to older domains. We have found 426 different annotated young domains, totalling 995 domain occurrences, which represent about 12.3% of all human domains. We have observed that 61.3% of them arose in newly formed genes, while the remaining 38.7% are found combined with older domains, and have very likely emerged in the context of a previously existing protein. Young domains are preferentially located at the N-terminus of the protein, indicating that, at least in vertebrates, novel functional sequences often emerge there. Furthermore, young domains show significantly higher non-synonymous to synonymous substitution rates than older domains using human and mouse orthologous sequence comparisons. This is also true when we compare young and old domains located in the same protein, suggesting that recently arisen domains tend to evolve in a less constrained manner than older domains. CONCLUSIONS: We conclude that proteins tend to gain domains over time, becoming progressively longer. We show that many proteins are made of domains of different age, and that the fastest evolving parts correspond to the domains that have been acquired more recently.
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Project description:The PspC and Hic proteins of Streptococcus pneumoniae are some of the most variable microbial immune evasion proteins identified to date. Due to structural similarities and conserved binding profiles, it was assumed for a long time that these pneumococcal surface proteins represent a protein family comprised of eleven subgroups. Recently, however, the evaluation of more proteins revealed a greater diversity of individual proteins. In contrast to previous assumptions a pattern evaluation of six PspC and five Hic variants, each representing one of the previously defined subgroups, revealed distinct structural and likely functionally regions of the proteins, and identified nine new domains and new domain alternates. Several domains are unique to PspC and Hic variants, while other domains are also present in other virulence factors encoded by pneumococci and other bacterial pathogens. This knowledge improved pattern evaluation at the level of full-length proteins, allowed a sequence comparison at the domain level and identified domains with a modular composition. This novel strategy increased understanding of individual proteins variability and modular domain composition, enabled a structural and functional characterization at the domain level and furthermore revealed substantial structural differences between PspC and Hic proteins. Given the exceptional genomic diversity of the multifunctional PspC and Hic proteins a detailed structural and functional evaluation need to be performed at the strain level. Such knowledge will also be useful for molecular strain typing and characterizing PspC and Hic proteins from new clinical S. pneumoniae strains.
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Project description:BackgroundProtein structures are comprised of modular elements known as domains. These units are used and re-used over and over in nature, and usually serve some particular function in the structure. Thus it is useful to be able to break up a protein of interest into its component domains, prior to similarity searching for example. Numerous computational methods exist for doing so, but most operate only on a single protein chain and many are limited to making a series of cuts to the sequence, while domains can and do span multiple chains.ResultsThis study presents a novel clustering-based approach to domain identification, which works equally well on individual chains or entire complexes. The method is simple and fast, taking only a few milliseconds to run, and works by clustering either vectors representing secondary structure elements, or buried alpha-carbon positions, using average-linkage clustering. Each resulting cluster corresponds to a domain of the structure. The method is competitive with others, achieving 70% agreement with SCOP on a large non-redundant data set, and 80% on a set more heavily weighted in multi-domain proteins on which both SCOP and CATH agree.ConclusionsIt is encouraging that a basic method such as this performs nearly as well or better than some far more complex approaches. This suggests that protein domains are indeed for the most part simply compact regions of structure with a higher density of buried contacts within themselves than between each other. By representing the structure as a set of points or vectors in space, it allows us to break free of any artificial limitations that other approaches may depend upon.
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Project description:BackgroundProtein domains are protein regions that are shared among different proteins and are frequently functionally and structurally independent from the rest of the protein. Novel domain combinations have a major role in evolutionary innovation. However, the relative contributions of the different molecular mechanisms that underlie domain gains in animals are still unknown. By using animal gene phylogenies we were able to identify a set of high confidence domain gain events and by looking at their coding DNA investigate the causative mechanisms.ResultsHere we show that the major mechanism for gains of new domains in metazoan proteins is likely to be gene fusion through joining of exons from adjacent genes, possibly mediated by non-allelic homologous recombination. Retroposition and insertion of exons into ancestral introns through intronic recombination are, in contrast to previous expectations, only minor contributors to domain gains and have accounted for less than 1% and 10% of high confidence domain gain events, respectively. Additionally, exonization of previously non-coding regions appears to be an important mechanism for addition of disordered segments to proteins. We observe that gene duplication has preceded domain gain in at least 80% of the gain events.ConclusionsThe interplay of gene duplication and domain gain demonstrates an important mechanism for fast neofunctionalization of genes.
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