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Promoter-sharing by different genes in human genome--CPNE1 and RBM12 gene pair as an example.

Yang W, Ng P, Zhao M, Wong TK, Yiu SM, Lau YL - BMC Genomics (2008)

Bottom Line: In a whole genome analysis of alternative splicing events, we found that two distinct genes, copine I (CPNE1) and RNA binding motif protein 12 (RBM12), share the most 5' exons and therefore the promoter region in human.Conservation of this genomic structure in evolutionary courses indicates potential functional interaction between the two genes.More than 20 other gene pairs in human genome were found to have the similar genomic structure in a genome-wide analysis, and it may represent a unique pattern of genomic arrangement that may affect expression regulation of the corresponding genes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Paediatrics & Adolescent Medicine, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, PR China. yangwl@hkucc.hku.hk

ABSTRACT

Background: Regulation of gene expression plays important role in cellular functions. Co-regulation of different genes may indicate functional connection or even physical interaction between gene products. Thus analysis on genomic structures that may affect gene expression regulation could shed light on the functions of genes.

Results: In a whole genome analysis of alternative splicing events, we found that two distinct genes, copine I (CPNE1) and RNA binding motif protein 12 (RBM12), share the most 5' exons and therefore the promoter region in human. Further analysis identified many gene pairs in human genome that share the same promoters and 5' exons but have totally different coding sequences. Analysis of genomic and expressed sequences, either cDNAs or expressed sequence tags (ESTs) for CPNE1 and RBM12, confirmed the conservation of this phenomenon during evolutionary courses. The co-expression of the two genes initiated from the same promoter is confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) in different tissues in both human and mouse. High degrees of sequence conservation among multiple species in the 5'UTR region common to CPNE1 and RBM12 were also identified.

Conclusion: Promoter and 5'UTR sharing between CPNE1 and RBM12 is observed in human, mouse and zebrafish. Conservation of this genomic structure in evolutionary courses indicates potential functional interaction between the two genes. More than 20 other gene pairs in human genome were found to have the similar genomic structure in a genome-wide analysis, and it may represent a unique pattern of genomic arrangement that may affect expression regulation of the corresponding genes.

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Related in: MedlinePlus

Phylogenetics analysis of expansion of the CPNE and RBM12 families. Protein sequences of the two gene families from various species were aligned using ClustalX. The aligned sequences were analyzed by MrBayes 3.1.2 for their phylogenetic distances and displayed by TreeView. The numbers shown on each branch are the posterior probabilities of the phylogenetic relationship. The circle marked the genes that shared promoters between CPNE1 and RBM12.
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Figure 2: Phylogenetics analysis of expansion of the CPNE and RBM12 families. Protein sequences of the two gene families from various species were aligned using ClustalX. The aligned sequences were analyzed by MrBayes 3.1.2 for their phylogenetic distances and displayed by TreeView. The numbers shown on each branch are the posterior probabilities of the phylogenetic relationship. The circle marked the genes that shared promoters between CPNE1 and RBM12.

Mentions: In an effort to examine the evolutionary changes of the two gene families, we have extracted and compared the predicted protein sequences of the paralogs and orthologs for these two genes from various species. Protein sequences for these two genes in different species were predicted from corresponding cDNA or EST sequences. The sequences were aligned by the multiple sequence alignment program ClustalX, and the alignment file was used for predicting the phylogenetic distances of different proteins using MrBayes (Figure 2). It is clear from the phylogenetic tree that, during the evolutionary courses starting from fish, RBM12 family expanded to RBM12 and RBM12B, and CPNE family expanded to 9 paralogs from Copine I to IX. Sequences from other species, such as C. elegans and C. intestinalis are much more divergent and do not group with any of the subgroups in either of the two gene families. It seems that the expansion of the two gene families started with fish, and CPNE1 and RBM12 may evolve together functionally with conserved promoter-sharing and co-regulation. From the phylogenetic distances, it is also interesting to note that among the paralogous CPNE genes, mammal CPNE1 sequences diverged very much from their counterparts in chicken, frog, and zebrafish (circled group in Fig. 2B), more so than in other CPNE genes, indicating that mammal CPNE1 may have evolved new functions much different than those in other species.


Promoter-sharing by different genes in human genome--CPNE1 and RBM12 gene pair as an example.

Yang W, Ng P, Zhao M, Wong TK, Yiu SM, Lau YL - BMC Genomics (2008)

Phylogenetics analysis of expansion of the CPNE and RBM12 families. Protein sequences of the two gene families from various species were aligned using ClustalX. The aligned sequences were analyzed by MrBayes 3.1.2 for their phylogenetic distances and displayed by TreeView. The numbers shown on each branch are the posterior probabilities of the phylogenetic relationship. The circle marked the genes that shared promoters between CPNE1 and RBM12.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2568002&req=5

Figure 2: Phylogenetics analysis of expansion of the CPNE and RBM12 families. Protein sequences of the two gene families from various species were aligned using ClustalX. The aligned sequences were analyzed by MrBayes 3.1.2 for their phylogenetic distances and displayed by TreeView. The numbers shown on each branch are the posterior probabilities of the phylogenetic relationship. The circle marked the genes that shared promoters between CPNE1 and RBM12.
Mentions: In an effort to examine the evolutionary changes of the two gene families, we have extracted and compared the predicted protein sequences of the paralogs and orthologs for these two genes from various species. Protein sequences for these two genes in different species were predicted from corresponding cDNA or EST sequences. The sequences were aligned by the multiple sequence alignment program ClustalX, and the alignment file was used for predicting the phylogenetic distances of different proteins using MrBayes (Figure 2). It is clear from the phylogenetic tree that, during the evolutionary courses starting from fish, RBM12 family expanded to RBM12 and RBM12B, and CPNE family expanded to 9 paralogs from Copine I to IX. Sequences from other species, such as C. elegans and C. intestinalis are much more divergent and do not group with any of the subgroups in either of the two gene families. It seems that the expansion of the two gene families started with fish, and CPNE1 and RBM12 may evolve together functionally with conserved promoter-sharing and co-regulation. From the phylogenetic distances, it is also interesting to note that among the paralogous CPNE genes, mammal CPNE1 sequences diverged very much from their counterparts in chicken, frog, and zebrafish (circled group in Fig. 2B), more so than in other CPNE genes, indicating that mammal CPNE1 may have evolved new functions much different than those in other species.

Bottom Line: In a whole genome analysis of alternative splicing events, we found that two distinct genes, copine I (CPNE1) and RNA binding motif protein 12 (RBM12), share the most 5' exons and therefore the promoter region in human.Conservation of this genomic structure in evolutionary courses indicates potential functional interaction between the two genes.More than 20 other gene pairs in human genome were found to have the similar genomic structure in a genome-wide analysis, and it may represent a unique pattern of genomic arrangement that may affect expression regulation of the corresponding genes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Paediatrics & Adolescent Medicine, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, PR China. yangwl@hkucc.hku.hk

ABSTRACT

Background: Regulation of gene expression plays important role in cellular functions. Co-regulation of different genes may indicate functional connection or even physical interaction between gene products. Thus analysis on genomic structures that may affect gene expression regulation could shed light on the functions of genes.

Results: In a whole genome analysis of alternative splicing events, we found that two distinct genes, copine I (CPNE1) and RNA binding motif protein 12 (RBM12), share the most 5' exons and therefore the promoter region in human. Further analysis identified many gene pairs in human genome that share the same promoters and 5' exons but have totally different coding sequences. Analysis of genomic and expressed sequences, either cDNAs or expressed sequence tags (ESTs) for CPNE1 and RBM12, confirmed the conservation of this phenomenon during evolutionary courses. The co-expression of the two genes initiated from the same promoter is confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) in different tissues in both human and mouse. High degrees of sequence conservation among multiple species in the 5'UTR region common to CPNE1 and RBM12 were also identified.

Conclusion: Promoter and 5'UTR sharing between CPNE1 and RBM12 is observed in human, mouse and zebrafish. Conservation of this genomic structure in evolutionary courses indicates potential functional interaction between the two genes. More than 20 other gene pairs in human genome were found to have the similar genomic structure in a genome-wide analysis, and it may represent a unique pattern of genomic arrangement that may affect expression regulation of the corresponding genes.

Show MeSH
Related in: MedlinePlus