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Open Access Highly Accessed Research article

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

Zhengyuan Wang1, Dante Zarlenga2, John Martin1, Sahar Abubucker1 and Makedonka Mitreva134*

Author affiliations

1 The Genome Institute, Washington University School of Medicine, 4444 Forest Park Blvd, St. Louis, MO 63108, USA

2 U.S. Department of Agriculture, Agricultural Research Service/ANRI, Animal Parasitic Diseases Lab, Beltsville, MD, 20705, USA

3 Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63108, USA

4 Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108, USA

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Citation and License

BMC Evolutionary Biology 2012, 12:138  doi:10.1186/1471-2148-12-138

Published: 3 August 2012



Proteins convey the majority of biochemical and cellular activities in organisms. Over the course of evolution, proteins undergo normal sequence mutations as well as large scale mutations involving domain duplication and/or domain shuffling. These events result in the generation of new proteins and protein families. Processes that affect proteome evolution drive species diversity and adaptation. Herein, change over the course of metazoan evolution, as defined by birth/death and duplication/deletion events within protein families and domains, was examined using the proteomes of 9 metazoan and two outgroup species.


In studying members of the three major metazoan groups, the vertebrates, arthropods, and nematodes, we found that 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 most lineages and at all terminal lineages. This resulted in a weak correlation between protein family birth and domain birth; 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. The ratio of protein family birth to protein domain birth (domain shuffling index) suggests that shuffling had a more demonstrable effect on 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; however, the speed of adaptation among the different lineages was relatively invariant. Evaluating the functions of protein families that appeared or disappeared at the last common ancestors (LCAs) of the three metazoan clades supports a correlation with organism adaptation. Furthermore, bursts of new protein families and domains in the LCAs of metazoans and vertebrates are consistent with whole genome duplications.


Metazoan speciation and adaptation were explored by birth/death and duplication/deletion events among protein families and domains. Our results provide insights into protein evolution and its bearing on metazoan evolution.

Proteins; Domains; Evolution; Metazoa; Vertebrates; Arthropods; Nematodes