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Published on: May 31, 2011
Comparative Genomics Provides Insights into the Evolutionary Origin and Structural Diversification of Steroid
Phelelani Erick Ngcobo1, Kwanele Zulu1, Nondumiso Silindokuhle Mabuyakhulu1
1Department of Biochemistry and Microbiology, Faculty of Science, Agriculture and Engineering, University of Zululand, Empangeni 3886, South Africa.
None:
Steroid Receptor Coactivators (SRCs) are members of the p160 nuclear receptor coactivator family and play essential roles in regulating transcription, development, metabolism, reproduction, and disease. However, their evolutionary origin and diversification remain poorly understood. Here, we employed a comprehensive comparative genomics approach to investigate the evolution of SRC-1, SRC-2, and SRC-3 across the domains of life. Evaluation of domain-based screening approaches showed that the NCBI Batch Web CD-Search Tool clearly distinguished domains among the three SRC family members. Genome-wide analyses identified 298 canonical SRC proteins in vertebrates, revealing distinct taxonomic distributions among the three paralogs. Comparative analyses of LXXLL motifs suggested both conserved and paralog-specific patterns associated with functional diversification. Analysis of more than 20,000 proteins, including over 4000 SRC-associated domain-containing proteins, revealed a widespread distribution of SRC-associated domains across diverse taxa. These findings support the hypothesis that pre-existing protein modules distributed across diverse taxa may have contributed to the assembly of canonical vertebrate SRC proteins through progressive domain acquisition and recombination. Phylogenetic analyses showed that SRC-1, SRC-2, and SRC-3 form distinct monophyletic clades, consistent with diversification through ancient gene duplication. Overall, these findings provide a comparative genomic framework for investigating the origin, structural evolution, and functional diversification of vertebrate SRC proteins while generating testable hypotheses regarding their evolutionary history.
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