Comparative genomics of the human and Fugu voltage-gated calcium channel alpha1-subunit gene family reveals greater diversity in Fugu.

Extensive search for the orthologs of 10 human voltage-gated calcium channel (VGCC) alpha(1)-subunit genes in the Fugu genome sequence revealed 21 alpha(1)-subunit genes in the compact genome of Fugu. Subtype classification of the identified Fugu alpha(1) orthologs based on phylogenetic analysis, genomic organization and sequence comparison of the most divergent II/III loop and the C-terminal regions of the alpha(1)-subunits indicated extra copies of alpha(1S)-, alpha(1D)-, alpha(1F)-, alpha(1A)-, alpha(1E)-, alpha(1H)- and alpha(1G)-subunit genes. Phylogenetic analysis reveals that this is likely due to fish lineage specific alpha(1)-subunit subtype duplication. Sequence comparison shows that many of the structural features characteristic of VGCC and specific channel subtypes are also present in the Fugu alpha(1)-subunits. All the Fugu alpha(1)-subunits showed similar expression profile to that of the mammalian alpha(1)-subunits except for Fugu alpha(1S), alpha(1A), alpha(1B) and alpha(1H) which have a more widespread tissue distribution. These results indicate that Fugu, a lower vertebrate, has more extensive channel heterogeneity compared to human.