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PNAS 105 (28): 9680-9684

Copyright © 2008 by the National Academy of Sciences.

Evolution of the phospho-tyrosine signaling machinery in premetazoan lineages

David Pincus*, Ivica Letunic{dagger}, Peer Bork{dagger}, and Wendell A. Lim*,{ddagger}

*Department of Cellular and Molecular Pharmacology, University of California, 600 16th Street, San Francisco, CA 94158; and {dagger}European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany

Figure 1
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Fig. 1. Phospho-tyrosine signaling machinery in different eukaryotic lineages. (a) P-Tyr signaling systems are built from a three-component system comprised of tyrosine kinase (writer), tyrosine phosphatase (eraser) and Src homology 2 (reader) domains. (b) Number of proteins containing TyrK, PTP, or SH2 domains by species. Only choanoflagellates and metazoans have high numbers of all three domains. All other premetazoans only have small numbers of PTP and SH2 domain proteins (no TyrK). These data imply an early evolution of PTP and SH2 domains, followed by an expansion in all domains only after invention of the TyrK domain (white circle). Protein numbers are lower-bound estimates as predicted by the SMART domain identification resource.


Figure 2
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Fig. 2. Pairwise domain combinations in P-Tyr signaling proteins by species. (a) Domains that cooccur in the same ORF as TyrK, SH2, and PTP domains provide functional contexts for these query domains and give clues to the usage of the P-Tyr signaling machinery across different genomes. Comparison of domain combinations between species reveals conserved and divergent functions. (b) Clustering diagram of pairwise combinations by species, using TyrK, PTP, and SH2 as query domains. Darker boxes indicate higher number of occurences of that combination in the genome. Combinations are clustered based on cooccurence in similar sets of species. Combinations easily cluster into classes, such as shared core, metazoan only, M. brevicollis (choanoflagellate) only, and N. vectensis (cnidarian) only. For all three query domains, M. brevicollis (Mbr) and N. vectensis (Nvec) have a large set of highly divergent domain combinations that are not observed in higher metazoans.


Figure 3
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Fig. 3. Evolution of domain architectues: conservation, expansion and divergence. (a) Examples of domain architectures by class. Examples are organized in a Venn diagram, showing overlapping and unique architectures in different lineages. A key of domains types is given in Fig. S2. (b) Circles in the trees indicate occurrence of the given architecture in a particular species. (Upper) Gradual accretion of more complex architecture in higher organisms (vertical expansion). (Lower) A case where simple two domain precursors diverged into independent branches between choanoflagellates and metazoans.


Figure 4
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Fig. 4. Model: Timeline for the evolution of the P-Tyr signaling system. Encoding potential of the P-Tyr system is shown in orange. The number of P-Tyr signaling proteins is shown in gray. Timeline starts with early eukaryotes, which have only PTP and SH2 signaling molecules and thus only low encoding potential. Upon the appearance of TyrK, however, encoding potential of the system abruptly increases, leading to expansion of number of P-Tyr signaling proteins. Branching between choanoflagellate and metazoan lineages is likely to have occurred while there was still significant untapped encoding potential in P-Tyr signaling systems.


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