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Abstract
BackgroundThroughout 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.ResultsWe 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.ConclusionSix 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.
Highlights
LIM is an ancient eukaryotic protein domain that originated prior to the last common ancestor of plants, fungi, amoebae, and animals
A protein family is usually defined as containing all proteins that descended from a single ancestral protein in the last common ancestor to bilaterians, while classes reflect deep evolutionary relationships between multi-domain proteins with distinct domain architectures
We divided the previously defined groups of LIM domains into 14 classes (ABLIM, CRP, ENIGMA, EPLIN, LASP, LIMK, LHX, LMO, LMO7, MICAL, PXN, PINCH, TES, ZXN)
Summary
LIM is an ancient eukaryotic protein domain that originated prior to the last common ancestor of plants, fungi, amoebae, and animals. Many LIM proteins shuttle to the nucleus, where they regulate gene expression and cell fate decisions [6,7] Given their roles in focal adhesion dynamics, LIM proteins are prominent in tissues having elevated levels of cell-cell interactions (e.g., striated muscle; reviewed in [8,9]). Their influence on intercellular communication makes them crucial to processes involving complex cellular navigation (e.g., axon guidance; [10]). Despite their fundamental roles in cellular processes and human disease, little is known about the evolution of the LIM superclass
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