TY - JOUR
T1 - Comparative analysis of function and interaction of transcription factors in nematodes
T2 - Extensive conservation of orthology coupled to rapid sequence evolution
AU - Haerty, Wilfried
AU - Artieri, Carlo
AU - Khezri, Navid
AU - Singh, Rama S.
AU - Gupta, Bhagwati P.
N1 - Funding Information:
We thank Phil Cumbo, Eric Schwartz, Jack Chen, and anonymous reviewers for constructive comments and advice. This work was supported by Natural Sciences and Engineering Research Council of Canada (NSERC) funds to BPG and RSS. CA is supported by an NSERC Post-Graduate Doctoral Scholarship and NK was an NSERC undergraduate summer trainee.
PY - 2008/8/27
Y1 - 2008/8/27
N2 - Background: Much of the morphological diversity in eukaryotes results from differential regulation of gene expression in which transcription factors (TFs) play a central role. The nematode Caenorhabditis elegans is an established model organism for the study of the roles of TFs in controlling the spatiotemporal pattern of gene expression. Using the fully sequenced genomes of three Caenorhabditid nematode species as well as genome information from additional more distantly related organisms (fruit fly, mouse, and human) we sought to identify orthologous TFs and characterized their patterns of evolution. Results: We identified 988 TF genes in C. elegans, and inferred corresponding sets in C. briggsae and C. remanei, containing 995 and 1093 TF genes, respectively. Analysis of the three gene sets revealed 652 3-way reciprocal 'best hit' orthologs (nematode TF set), approximately half of which are zinc finger (ZF-C2H2 and ZF-C4/NHR types) and HOX family members. Examination of the TF genes in C. elegans and C. briggsae identified the presence of significant tandem clustering on chromosome V, the majority of which belong to ZF-C4/NHR family. We also found evidence for lineage-specific duplications and rapid evolution of many of the TF genes in the two species. A search of the TFs conserved among nematodes in Drosophila melanogaster, Mus musculus and Homo sapiens revealed 150 reciprocal orthologs, many of which are associated with important biological processes and human diseases. Finally, a comparison of the sequence, gene interactions and function indicates that nematode TFs conserved across phyla exhibit significantly more interactions and are enriched in genes with annotated mutant phenotypes compared to those that lack orthologs in other species. Conclusion: Our study represents the first comprehensive genome-wide analysis of TFs across three nematode species and other organisms. The findings indicate substantial conservation of transcription factors even across distant evolutionary lineages and form the basis for future experiments to examine TF gene function in nematodes and other divergent phyla.
AB - Background: Much of the morphological diversity in eukaryotes results from differential regulation of gene expression in which transcription factors (TFs) play a central role. The nematode Caenorhabditis elegans is an established model organism for the study of the roles of TFs in controlling the spatiotemporal pattern of gene expression. Using the fully sequenced genomes of three Caenorhabditid nematode species as well as genome information from additional more distantly related organisms (fruit fly, mouse, and human) we sought to identify orthologous TFs and characterized their patterns of evolution. Results: We identified 988 TF genes in C. elegans, and inferred corresponding sets in C. briggsae and C. remanei, containing 995 and 1093 TF genes, respectively. Analysis of the three gene sets revealed 652 3-way reciprocal 'best hit' orthologs (nematode TF set), approximately half of which are zinc finger (ZF-C2H2 and ZF-C4/NHR types) and HOX family members. Examination of the TF genes in C. elegans and C. briggsae identified the presence of significant tandem clustering on chromosome V, the majority of which belong to ZF-C4/NHR family. We also found evidence for lineage-specific duplications and rapid evolution of many of the TF genes in the two species. A search of the TFs conserved among nematodes in Drosophila melanogaster, Mus musculus and Homo sapiens revealed 150 reciprocal orthologs, many of which are associated with important biological processes and human diseases. Finally, a comparison of the sequence, gene interactions and function indicates that nematode TFs conserved across phyla exhibit significantly more interactions and are enriched in genes with annotated mutant phenotypes compared to those that lack orthologs in other species. Conclusion: Our study represents the first comprehensive genome-wide analysis of TFs across three nematode species and other organisms. The findings indicate substantial conservation of transcription factors even across distant evolutionary lineages and form the basis for future experiments to examine TF gene function in nematodes and other divergent phyla.
UR - http://www.scopus.com/inward/record.url?scp=51349094325&partnerID=8YFLogxK
U2 - 10.1186/1471-2164-9-399
DO - 10.1186/1471-2164-9-399
M3 - Article
C2 - 18752680
AN - SCOPUS:51349094325
VL - 9
JO - BMC Genomics
JF - BMC Genomics
SN - 1471-2164
M1 - 399
ER -