TY - JOUR
T1 - Phylogenetic analysis of the neep21/calcyon/p19 family of endocytic proteins
T2 - Evidence for functional evolution in the vertebrate cns
AU - Muthusamy, Nagendran
AU - Ahmed, Sanaa A.
AU - Rana, Brinda K.
AU - Navarre, Sammy
AU - Kozlowski, David J
AU - Liberles, David A.
AU - Bergson, Clare M
N1 - Funding Information:
This work was supported by the NIH MH063271 (C.B.). This work was also funded by an institutional NIH-INBRE award to University of Wyoming and by NSF award 0743374 (DAL). We thank Haiqin Jin for her excellent technical support.
PY - 2009/10
Y1 - 2009/10
N2 - Endocytosis and vesicle trafficking are required for optimal neural transmission. Yet, little is currently known about the evolution of neuronal proteins regulating these processes. Here, we report the first phylogenetic study of NEEP21, calcyon, and P19, a family of neuronal proteins implicated in synaptic receptor endocytosis and recycling, as well as in membrane protein trafficking in the somatodendritic and axonal compartments of differentiated neurons. Database searches identified orthologs for P19 and NEEP21 in bony fish, but not urochordate or invertebrate phyla. Calcyon orthologs were only retrieved from mammalian databases and distant relatives from teleost fish. In situ localization of the P19 zebrafish ortholog, and extant progenitor of the gene family, revealed a CNS specific expression pattern. Based on non-synonymous nucleotide substitution rates, the calcyon genes appear to be under less intense negative selective pressure. Indeed, a functional group II WW domain binding motif was detected in primate and human calcyon, but not in non-primate orthologs. Sequencing of the calcyon gene from 80 human subjects revealed a non-synonymous single nucleotide polymorphism that abrogated group II WW domain protein binding. Altogether, our data indicate the NEEP21/calcyon/P19 gene family emerged, and underwent two rounds of gene duplication relatively late in metazoan evolution (but early in vertebrate evolution at the latest). As functional studies suggest NEEP21 and calcyon play related, but distinct roles in regulating vesicle trafficking at synapses, and in neurons in general, we propose the family arose in chordates to support a more diverse range of synaptic and behavioral responses.
AB - Endocytosis and vesicle trafficking are required for optimal neural transmission. Yet, little is currently known about the evolution of neuronal proteins regulating these processes. Here, we report the first phylogenetic study of NEEP21, calcyon, and P19, a family of neuronal proteins implicated in synaptic receptor endocytosis and recycling, as well as in membrane protein trafficking in the somatodendritic and axonal compartments of differentiated neurons. Database searches identified orthologs for P19 and NEEP21 in bony fish, but not urochordate or invertebrate phyla. Calcyon orthologs were only retrieved from mammalian databases and distant relatives from teleost fish. In situ localization of the P19 zebrafish ortholog, and extant progenitor of the gene family, revealed a CNS specific expression pattern. Based on non-synonymous nucleotide substitution rates, the calcyon genes appear to be under less intense negative selective pressure. Indeed, a functional group II WW domain binding motif was detected in primate and human calcyon, but not in non-primate orthologs. Sequencing of the calcyon gene from 80 human subjects revealed a non-synonymous single nucleotide polymorphism that abrogated group II WW domain protein binding. Altogether, our data indicate the NEEP21/calcyon/P19 gene family emerged, and underwent two rounds of gene duplication relatively late in metazoan evolution (but early in vertebrate evolution at the latest). As functional studies suggest NEEP21 and calcyon play related, but distinct roles in regulating vesicle trafficking at synapses, and in neurons in general, we propose the family arose in chordates to support a more diverse range of synaptic and behavioral responses.
KW - Group II WW domain
KW - Ka/Ks
KW - Primate innovation
KW - Single nucleotide polymorphism
KW - Synaptic plasticity
KW - Transcytosis
KW - Zebra fish
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U2 - 10.1007/s00239-009-9273-y
DO - 10.1007/s00239-009-9273-y
M3 - Article
C2 - 19760447
AN - SCOPUS:70449528323
SN - 0022-2844
VL - 69
SP - 319
EP - 332
JO - Journal of Molecular Evolution
JF - Journal of Molecular Evolution
IS - 4
ER -