Exploring metazoan evolution through dynamic and holistic changes in protein families and domains

Authors: WANG, ZHENGYUAN - Washington University School Of Medicine; Zarlenga, Dante; MARTIN, JOHN - Washington University School Of Medicine; ABUBUCKER, SAHAR - Washington University School Of Medicine; MITREVA, MAKEDONKA - Washington University School Of Medicine

Submitted to: PLoS Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/19/2012
Publication Date: 8/3/2012
Citation: Wang, Z., Zarlenga, D.S., Martin, J., Abubucker, S., Mitreva, M. 2012. Exploring metazoan evolution through dynamic and holistic changes in protein families and domains. PLoS Genetics. 12:138.

Interpretive Summary: Proteins convey the majority of biochemical and cellular activities in organisms. Their structural and functional units are defined as domains where each protein may contain a single or multiple domains. Over the course of evolution, proteins undergo mutations, duplications, and domain shuffling which can result in the generation of new proteins and new protein families through natural selection. The interplay between the different protein evolutionary events creates complicated mechanisms that help govern speciation and adaptation of organisms. As such, analyzing these changes can greatly improve our understanding of protein evolution, nematode diversity and adaptation. To this end, we examined the complete proteomes of 11 species, which included 9 representatives from three major phyla, the vertebrates, arthropods and nematodes, and two additional outgroups. This is the first large-scale analysis of the evolution of proteins, protein families, and domains in the kingdom Metazoa by reconstructing the birth (appearance) and death (disappearance) of protein families and domains in the lineages defined. Results showed that lineages leading to mammals exhibited consistent increases in protein family complexity during evolution. Results also illustrated that domain shuffling had a greater impact on protein family complexity in nematodes than in other metazoans, and that protein redundancy may be critical for evolutionary changes controlled by domain shuffling. By relating the evolutionary events to the functions of the proteins/domains involved, the results exposed the adaptive roles of these events. Overall, our study provides new insights into protein evolution associated with metazoan speciation. This work is particularly important to both scientists and the drug industry in that it can provide new protein targets for developing better anthelmintics and therefore better disease treatment and control.

Technical Abstract: Understanding proteome evolution is important for deciphering processes that drive species diversity and adaptation. Herein, the dynamics of change in protein families and protein domains over the course of metazoan evolution was explored. Change, as defined by birth/death and duplication/deletion events within protein families and domains, was studied using the proteomes of 9 metazoan and two outgroup species. Results showed that members of the three major metazoan groups i.e. vertebrates, arthropods, and nematodes, exhibited different evolutionary patterns as defined by these changes. In general, the number of protein families increased at the majority of lineages over the course of metazoan evolution where the magnitude of these increases was greatest at the lineages leading to mammals. In contrast, the number of protein domains decreased at the majority of lineages, and in particular, at all terminal lineages. This resulted in a weak correlation between protein family birth and domain birth. Likewise, the correlation between protein family birth and protein family member duplication was also weak; however, the correlation between domain birth and domain member duplication was quite strong. These data suggest that domain birth and protein family birth occur via different mechanisms, and that domain shuffling plays a role in the formation of protein families. Subsequent examination of the domain shuffling index within a lineage, defined by the ratio of protein family birth to protein domain birth, suggests that shuffling had a more demonstrable effect on the changes in protein families in nematodes and arthropods than in vertebrates. Through the contrast of high and low domain shuffling indices at the lineages of Trichinella spiralis and Gallus gallus, we propose a link between protein redundancy and evolutionary changes controlled by domain shuffling. Furthermore, bursts of new protein families and new domains in the LCAs of metazoans and vertebrates are consistent with whole genome duplications in these two lineages. Herein we provide new insights into protein evolution and its bearing on metazoan evolution.