Computational inference of functional relationships from multiple genomes : Drosophila carbonic anhydrases.
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Carbonic anhydrases (CAHs) are metalloenzymes which catalyze the reversible chemical reaction
between carbon dioxide and water to bicarbonate and a proton, which is crucial in pH homeostasis.
There are several CAH families in different protein classes with independent evolutionary origins.
In vertebrates, at least 15 isoforms exist, classified into cytoplasmic, mitochondrial, secreted, and
membrane-associated CAHs, and acatalytic CAH-related proteins. Invertebrates have a similar
multiplicity in their alpha CAH genes, but most of the isoforms have no direct equivalents within
vertebrate CAHs. Vertebrate CAHs are well characterized for their tissue distribution and functions,
but no functional analyses of a complete set of all CAH isoforms have been made in any
invertebrate species. This study deals with in silico functional prediction based on the evolution of
15 alpha CAH ortholog groups in 22 complete drosophila genomes. Additionally, molecular
evolution analysis detected no significant positively selected sites in the sequence of invertebrates.
Different bioinformatics analyses were done to predict the subcellular localization, multiple
sequence analysis, phylogenetic analysis, and alpha CAH were functionally categorized which was
shown to be reliable to the expression data from FlyBase. The gene set whose gene expression is
specific for male reproductive organs, for the spermatheca, have found to be highly statistically
correlated. The molecular evolution analysis of CAH gene family in invertebrate detected no
significant positively selected sites by BEB analysis in PAML. This novel bioinformatics method
for functional grouping has similarity with the expression data of drosophila species. This method
can be further modified and used to identify the functional classification of other gene families.