5 Metazoan Complexity
147
Proterospongia-like species (using EST data) (Abedin and King 2008, King et al.
2003, 2008).
The most recent Monosiga brevicollis genome annotation (April 2008) listed 78
protein domains that are shared exclusively with metazoans but are absent from
plants, fungi or slime molds (although some resemble bacterial protein domains)
underscoring the close relatedness of choanoflagellates and metazoans (King et al.
2008). These domains are found in metazoan cell adhesion proteins (e.g. extracellular cadherin, sugar-binding C-type lectins, immunoglobulin, and integrin α domains)
and extra-cellular matrix (ECM) components (fibronectins) including basement
membrane elements (several collagen types and laminins). The respective functional
domains therefore originated before the choanoflagellate-metazoan split, although
many occur in choanoflagellate-specific combinations, as found for extracellular
cadherin domains (ECDs)-containing proteins. However, some ECDs are conserved
in Fat-type cadherins (conserved in sponges, cnidarians and bilaterians) and in a
Hedgehog-related protein so far restricted to sponges and cnidarians (hedgling, see
also below and Fig. 5.2) (Abedin and King 2008, King et al. 2008). Notably, “classical” metazoan-type cadherins with a highly conserved cadherin cytoplasmic domain
have not been found in M. brevicollis (Abedin and King 2008). Also integrin β, a
metazoan-specific cell adhesion receptor domain, and the ECM component laminin
B(IV) are absent (King et al. 2008).
Whereas M. brevicollis possesses a surprisingly rich repertoire of metazoan
cell adhesion and ECM domains, most of the intracellular signalling cascades
associated with metazoan cell–cell communication are missing or highly divergent in choanoflagellates. Clear Wnt, TGF-β ligands or nuclear hormone receptor orthologues, present as large families in metazoans, are missing from the
M. brevicollis genome, while other animal signalling pathways (JAK/STAT,
Hedgehog, Delta/Notch) are incomplete. For some multidomain signalling pathway
components (e.g. Notch or Hedgehog proteins), single domains are encoded in the
M. brevicollis genome, but as for cell adhesion proteins, mostly not in metazoancharacteristic combinations. As for tyrosine kinase signal transduction pathways,
M. brevicollis exhibits the largest number of tyrosine kinases and receptors, regulatory phosphatases and phospho-tyrosine-binding SH2 domain proteins (signal
transducers) so far discovered in a single species. However, they appear to be largely
divergent from metazoan members of the tyrosine kinase pathway (King et al. 2003,
2008, Manning et al. 2008). This is evident by the lack of clear orthologues, differences in regulation of tyrosine-kinase signalling and a large set of choanoflagellate
tyrosine-kinase domain combinations not found in metazoan proteins (King et al.
2008, Manning et al. 2008, Pincus et al. 2008, Segawa et al. 2006). An exception is
the conserved combination of intracellular tyrosine kinase domains and cytoplasmic
SH2 domains with extracellular cadherin and EGF domains (in e.g. hedgling) suggesting that tyrosine-kinase signaling can relay extracellular signals (Abedin and
King 2008, King et al. 2003). Functional assays have linked tyrosine kinase signalling to the regulation of the cell cycle by monitoring external food availability
(King et al. 2003).
147
Proterospongia-like species (using EST data) (Abedin and King 2008, King et al.
2003, 2008).
The most recent Monosiga brevicollis genome annotation (April 2008) listed 78
protein domains that are shared exclusively with metazoans but are absent from
plants, fungi or slime molds (although some resemble bacterial protein domains)
underscoring the close relatedness of choanoflagellates and metazoans (King et al.
2008). These domains are found in metazoan cell adhesion proteins (e.g. extracellular cadherin, sugar-binding C-type lectins, immunoglobulin, and integrin α domains)
and extra-cellular matrix (ECM) components (fibronectins) including basement
membrane elements (several collagen types and laminins). The respective functional
domains therefore originated before the choanoflagellate-metazoan split, although
many occur in choanoflagellate-specific combinations, as found for extracellular
cadherin domains (ECDs)-containing proteins. However, some ECDs are conserved
in Fat-type cadherins (conserved in sponges, cnidarians and bilaterians) and in a
Hedgehog-related protein so far restricted to sponges and cnidarians (hedgling, see
also below and Fig. 5.2) (Abedin and King 2008, King et al. 2008). Notably, “classical” metazoan-type cadherins with a highly conserved cadherin cytoplasmic domain
have not been found in M. brevicollis (Abedin and King 2008). Also integrin β, a
metazoan-specific cell adhesion receptor domain, and the ECM component laminin
B(IV) are absent (King et al. 2008).
Whereas M. brevicollis possesses a surprisingly rich repertoire of metazoan
cell adhesion and ECM domains, most of the intracellular signalling cascades
associated with metazoan cell–cell communication are missing or highly divergent in choanoflagellates. Clear Wnt, TGF-β ligands or nuclear hormone receptor orthologues, present as large families in metazoans, are missing from the
M. brevicollis genome, while other animal signalling pathways (JAK/STAT,
Hedgehog, Delta/Notch) are incomplete. For some multidomain signalling pathway
components (e.g. Notch or Hedgehog proteins), single domains are encoded in the
M. brevicollis genome, but as for cell adhesion proteins, mostly not in metazoancharacteristic combinations. As for tyrosine kinase signal transduction pathways,
M. brevicollis exhibits the largest number of tyrosine kinases and receptors, regulatory phosphatases and phospho-tyrosine-binding SH2 domain proteins (signal
transducers) so far discovered in a single species. However, they appear to be largely
divergent from metazoan members of the tyrosine kinase pathway (King et al. 2003,
2008, Manning et al. 2008). This is evident by the lack of clear orthologues, differences in regulation of tyrosine-kinase signalling and a large set of choanoflagellate
tyrosine-kinase domain combinations not found in metazoan proteins (King et al.
2008, Manning et al. 2008, Pincus et al. 2008, Segawa et al. 2006). An exception is
the conserved combination of intracellular tyrosine kinase domains and cytoplasmic
SH2 domains with extracellular cadherin and EGF domains (in e.g. hedgling) suggesting that tyrosine-kinase signaling can relay extracellular signals (Abedin and
King 2008, King et al. 2003). Functional assays have linked tyrosine kinase signalling to the regulation of the cell cycle by monitoring external food availability
(King et al. 2003).