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Comparative genomic analysis of eutherian interferon-γ-inducible GTPases

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Abstract

The interferon-γ-inducible GTPases, IFGGs, are intracellular proteins involved in immune response against pathogens. A comprehensive comparative genomic review and analysis of eutherian IFGGs was carried out using public genomic sequences. The 64 eutherian IFGG genes were examined in detail and annotated. The eutherian IFGG promoter types were first catalogued followed by a phylogenetic analysis of eutherian IFGGs, which described five major IFGG clusters. The patterns of differential gene expansions and protein regions that may regulate IFGG catalytic features suggested a new classification of eutherian IFGGs. This mini-review has also provided new tests of reliability of public genomic sequences as well as tests of protein molecular evolution.

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Acknowledgements

MP would like to thank reviewers for their helpful comments.

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Authors and Affiliations

  1. Laboratory of Genomics, Centre of Animal Reproduction, 55 Heinzel St., 10000, Zagreb, Croatia

    Marko Premzl

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  1. Marko Premzl
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Correspondence to Marko Premzl.

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Supplementary data file 1

Gene annotations of eutherian IFGGs. A) Differential IFGG gene expansions. The relative IFGG gene orders and orientations are approximately shown for human, mouse, brown rat, domestic cattle and domestic dog. The grey triangles label IFGG putative coding sequences. B-I) Gene alignments of eutherian IFGGs. The VISTA plots of pairwise nucleotide alignments between base sequences that are shown on top of each alignment, and aligned sequences respectively, show degrees of pairwise sequence conservations, as indicated on right sides. The exons of base sequences are shown as indigo rectangles (translated sequences) or cyan rectangles (untranslated sequences). The genomic sequence regions that show conservation levels that exceed our cut-offs for detection of conserved sequences in pairwise alignments are labelled accordingly. The grey arrows indicate gene transcription directions. The conserved eutherian IFGG promoter type sequences, P1–P8, are labelled using rectangles. The mouse Ifgga1 exon 1B is labelled using brackets. BTA, domestic cattle chromosome; CFA, domestic dog chromosome; HSA, human chromosome; MMU, mouse chromosome; RNO, brown rat chromosome. (PDF 122 kb)

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Supplementary data file 2

Alignment of eutherian IFGGs. The reference sequence, mouse Ifgga1 invariant amino acid sites (white letters on violet background) and forward amino acid sites (white letters on red background) are labelled. The alignment positions that show 100 % conservation (white letters on black background), ≥70 % conservation (white letters on dark grey background) and ≥30 % conservation (black letters on grey background) are labelled, as explained in text. (PDF 205 kb)

Supplementary data file 3

Pairwise nucleotide identities of eutherian IFGGs. (DOC 67.2 kb)

Supplementary data file 4

Molecular evolution analysis of eutherian IFGGs. A) Mouse Ifgga1 residues. The reference sequence invariant amino acid sites (white letters on violet background) and forward amino acid sites (white letters on red background) are labelled. The secondary structure elements are labelled grey (Ghosh et al. 2004). The black triangles mark regions A1 (amino acids 15–67), G (amino acids 68–250) and A2 (amino acids 251–411). The amino acid site clusters are labelled. The 18 amino acids implicated in GTP binding are labelled using #s. B-E) Analysis of mouse Ifgg1 crystal structure. In amino acid site clusters, the reference sequence invariant amino acid sites are labelled violet, forward amino acid sites are labelled red and compensatory amino acid sites are labelled white. B) Ribbon representation of mouse Ifgg1 effector domain. The amino acid site clusters 1 and 6–8 are labelled. The same view is shown as van der Waals representation in C. D) Ribbon representation of mouse Ifgg1 GTPase domain. The amino acid site clusters 2–5 are labelled. The GTP analogue guanosine-5′-(βγ-imino)triphosphate (GppNHp) and Mg++ are labelled white. E) Amino acid site clusters 2–5 shown as van der Waals representations. The GppNHp and Mg++ are labelled white. (PDF 194 kb)

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Premzl, M. Comparative genomic analysis of eutherian interferon-γ-inducible GTPases. Funct Integr Genomics 12, 599–607 (2012). https://doi.org/10.1007/s10142-012-0291-2

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