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Comparative Study
, 7 (3), e33261

The Diversification of the LIM Superclass at the Base of the Metazoa Increased Subcellular Complexity and Promoted Multicellular Specialization

Comparative Study

The Diversification of the LIM Superclass at the Base of the Metazoa Increased Subcellular Complexity and Promoted Multicellular Specialization

Bernard J Koch et al. PLoS One.


Background: Throughout evolution, the LIM domain has been deployed in many different domain configurations, which has led to the formation of a large and distinct group of proteins. LIM proteins are involved in relaying stimuli received at the cell surface to the nucleus in order to regulate cell structure, motility, and division. Despite their fundamental roles in cellular processes and human disease, little is known about the evolution of the LIM superclass.

Results: We have identified and characterized all known LIM domain-containing proteins in six metazoans and three non-metazoans. In addition, we performed a phylogenetic analysis on all LIM domains and, in the process, have identified a number of novel non-LIM domains and motifs in each of these proteins. Based on these results, we have formalized a classification system for LIM proteins, provided reasonable timing for class and family origin events; and identified lineage-specific loss events. Our analysis is the first detailed description of the full set of LIM proteins from the non-bilaterian species examined in this study.

Conclusion: Six of the 14 LIM classes originated in the stem lineage of the Metazoa. The expansion of the LIM superclass at the base of the Metazoa undoubtedly contributed to the increase in subcellular complexity required for the transition from a unicellular to multicellular lifestyle and, as such, was a critically important event in the history of animal multicellularity.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.


Figure 1
Figure 1. Domain architectures of LIM superclass of proteins.
LIM domains are represented as blue ovals, non-LIM PFAM domains as grey shapes, and motifs and conserved regions as yellow boxes. In each case, the order of the domains or motifs is correct, but the spacing and length is not to scale (see Table S1 for actual coordinates). LIM domains from one class or family that appear to be related to another LIM domain from another class or family are connected with a red dashed line. Abbreviations are as follows: villin headpiece domain (VHP), glycine rich region (Gly), zasp motif (ZM), alp motif (AM), EPLIN motif (EM), nebulin repeat (Neb), SRC homology 3 domain (SH3), homeodomain (HD), calponin homology domain (CH), leucine-aspartate repeat (LD), PINCH motif (PM), TES motif A1 (TMA1), TES motif A2 (TMA2), ZYX motif (ZyM). For loss events see Table S1.
Figure 2
Figure 2. Origin of LIM classes and families.
Arrows indicate the stem lineage where a particular group of LIM proteins originated. Classes are denoted in capital letters and are not shown in parentheses. Families are denoted in lower case and appear after the class. The first appearance of a class is in red, while subsequent appearances of families of that class are in blue. The tree is based on the ParaHoxozoa hypothesis . The phyla represented are as follows: Capsaspora ocwazarki (Filasterea), Salpingoeca rosetta (Choanoflagellatea), Monosiga brevicollis (Choanoflagellatea), Amphimedon queenslandica (Porifera), Mnemiopsis leidyi (Ctenophora), Nematostella vectensis (Cnidaria), Trichoplax adhaerens (Placozoa), Drosophila melanogaster (Arthropoda), and Homo sapiens (Vertebrata).
Figure 3
Figure 3. LIM domain cladogram.
Alternating blue and grey coloring delineates homology groups; black regions are unclassified. For the homology group of each taxon, see Table S3. White circles with red outlines denote visually identified clades that contain a specific LIM domain conserved within a class or family. Colored circles indicate which species have taxa present within that manually annotated clade. For tip labels, branch lengths, and bootstrap values see Figures S2 and S3.
Figure 4
Figure 4. Presence and absence of LIM classes in our sampled species.
The left column represents classes (designations written in all caps) or families (designations written in title case and clustered by class). There is a break between columns representing non-metazoans and metazoans to highlight the small number of classes and families present in the non-metazoans. Blue squares represent presence of a particular class or family (row) in a particular species (column). A half-blue square indicates some uncertainty as to the whether or not a particular class or family is present. Notes on half-blue squares: (a) both Trichoplax ABLIM proteins lack a VHP domain; (b) the Capsaspora LIMK protein contains an extra TFIIA domain; (c) the Amphimedon, Monosiga, and Salpingoeca EPLIN proteins contain additional domains besides the EPLIN motif and LIM domain; (d) the Monosiga LASP protein contains an additional PH domain; (e) the Drosophila LMO7 contains only an LMO7-like LIM domain, but lacks a CH domain and a PDZ domain; (f) the Mnemiopsis ZYX protein contains extra DSL domains. ‡ Alp and Enigma are absent from Drosophila but they are both present in another protostome Capitella telata. * Tungus is absent from Homo sapiens, however we positively identified a Tungus protein in another deuterostome Branchiostoma floridae.

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