Limits...
The evolution and genomic landscape of CGB1 and CGB2 genes.

Hallast P, Rull K, Laan M - Mol. Cell. Endocrinol. (2006)

Bottom Line: The origin of completely novel proteins is a significant question in evolution.Two genes in this cluster (CGB1 and CGB2) exhibit nucleotide sequence similarity with the other LHB/CGB genes, but as a result of frameshifting are predicted to encode a completely novel protein.In silico prediction of putative transcription factor binding sites supports the hypothesis that CGB1 and CGB2 gene products are expressed in, and may contribute to, implantation and placental development.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia.

ABSTRACT
The origin of completely novel proteins is a significant question in evolution. The luteinizing hormone (LHB)/chorionic gonadotropin (CGB) gene cluster in humans contains a candidate example of this process. Two genes in this cluster (CGB1 and CGB2) exhibit nucleotide sequence similarity with the other LHB/CGB genes, but as a result of frameshifting are predicted to encode a completely novel protein. Our analysis of these genes from humans and related primates indicates a recent origin in the lineage specific to humans and African great apes. While the function of these genes is not yet known, they are strongly conserved between human and chimpanzee and exhibit three-fold lower diversity than LHB across human populations with no mutations that would disrupt the coding sequence. The 5'-upstream region of CGB1/2 contains most of the promoter sequence of hCGbeta plus a novel region proximal to the putative transcription start site. In silico prediction of putative transcription factor binding sites supports the hypothesis that CGB1 and CGB2 gene products are expressed in, and may contribute to, implantation and placental development.

Show MeSH

Related in: MedlinePlus

SNP patterns and fixed differences between human and great apes in CGB1 (A), CGB2 (B) and LHB (C) genes. Human polymorphic positions (vertical black bars) are marked as long bars for common SNPs (minor allele frequency >10%) and short bars for rare SNPs (<10%). For human and great ape comparison fixed differences (black arrows), non-synonymous changes (black arrows with an asterisk), SNPs found in apes (black triangle) and protein altering insertions/deletions are shown (exclamation mark).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2599907&req=5

fig2: SNP patterns and fixed differences between human and great apes in CGB1 (A), CGB2 (B) and LHB (C) genes. Human polymorphic positions (vertical black bars) are marked as long bars for common SNPs (minor allele frequency >10%) and short bars for rare SNPs (<10%). For human and great ape comparison fixed differences (black arrows), non-synonymous changes (black arrows with an asterisk), SNPs found in apes (black triangle) and protein altering insertions/deletions are shown (exclamation mark).

Mentions: Divergence of chimpanzee (C) and gorilla (G) CGB1, CGB2 and LHB from human (H) sequences (Table 2; H/C: across the genes 1.35–2.19%, exons 0.5–1.42%, introns 1.53–2.68; H/G: across the genes 1.44–3.00%, exons 1.42–4.04%, introns 1.36–3.31%) somewhat exceeds previous estimations. The average divergence across 53 autosomal intergenic regions has been reported 1.24 ± 0.07% for H/C and 1.62 ± 0.08% for H/G (Chen and Li, 2001). Human/chimpanzee comparison of 127 genes mapped to human chr. 21 resulted in estimates of overall divergence for coding sequences 0.75 ± 0.01% (range 0.53–2.05%), for exons 0.51% ± 0.02 (range 0.08–2.52%), for exon/intron junction 0.85 ± 0.02% (range 0.41–2.78%) for 5′-UTR 1.00% ± 0.10 and for 3′-UTR 0.93% ± 0.09 (Shi et al., 2003). Relatively high divergence (across the gene 5.39% compared to 3.08% reported for intergenic regions; Chen and Li, 2001) was also estimated between human and orangutan (O) for LHB including 11 non-synonymous changes. Higher interspecific divergence could result from the intraspecific gene conversion among highly homologous genes in the LHB/CGB cluster (Maston and Ruvolo, 2002; Hallast et al., 2005). For gorilla CGB2 gene approximately two fold higher sequence divergence for H/G compared to H/C largely arises from two gorilla-specific deletions (2 and 12 bp) increasing substantially the number of fixed nucleotide differences between species (Fig. 2; supplementary figure).


The evolution and genomic landscape of CGB1 and CGB2 genes.

Hallast P, Rull K, Laan M - Mol. Cell. Endocrinol. (2006)

SNP patterns and fixed differences between human and great apes in CGB1 (A), CGB2 (B) and LHB (C) genes. Human polymorphic positions (vertical black bars) are marked as long bars for common SNPs (minor allele frequency >10%) and short bars for rare SNPs (<10%). For human and great ape comparison fixed differences (black arrows), non-synonymous changes (black arrows with an asterisk), SNPs found in apes (black triangle) and protein altering insertions/deletions are shown (exclamation mark).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2599907&req=5

fig2: SNP patterns and fixed differences between human and great apes in CGB1 (A), CGB2 (B) and LHB (C) genes. Human polymorphic positions (vertical black bars) are marked as long bars for common SNPs (minor allele frequency >10%) and short bars for rare SNPs (<10%). For human and great ape comparison fixed differences (black arrows), non-synonymous changes (black arrows with an asterisk), SNPs found in apes (black triangle) and protein altering insertions/deletions are shown (exclamation mark).
Mentions: Divergence of chimpanzee (C) and gorilla (G) CGB1, CGB2 and LHB from human (H) sequences (Table 2; H/C: across the genes 1.35–2.19%, exons 0.5–1.42%, introns 1.53–2.68; H/G: across the genes 1.44–3.00%, exons 1.42–4.04%, introns 1.36–3.31%) somewhat exceeds previous estimations. The average divergence across 53 autosomal intergenic regions has been reported 1.24 ± 0.07% for H/C and 1.62 ± 0.08% for H/G (Chen and Li, 2001). Human/chimpanzee comparison of 127 genes mapped to human chr. 21 resulted in estimates of overall divergence for coding sequences 0.75 ± 0.01% (range 0.53–2.05%), for exons 0.51% ± 0.02 (range 0.08–2.52%), for exon/intron junction 0.85 ± 0.02% (range 0.41–2.78%) for 5′-UTR 1.00% ± 0.10 and for 3′-UTR 0.93% ± 0.09 (Shi et al., 2003). Relatively high divergence (across the gene 5.39% compared to 3.08% reported for intergenic regions; Chen and Li, 2001) was also estimated between human and orangutan (O) for LHB including 11 non-synonymous changes. Higher interspecific divergence could result from the intraspecific gene conversion among highly homologous genes in the LHB/CGB cluster (Maston and Ruvolo, 2002; Hallast et al., 2005). For gorilla CGB2 gene approximately two fold higher sequence divergence for H/G compared to H/C largely arises from two gorilla-specific deletions (2 and 12 bp) increasing substantially the number of fixed nucleotide differences between species (Fig. 2; supplementary figure).

Bottom Line: The origin of completely novel proteins is a significant question in evolution.Two genes in this cluster (CGB1 and CGB2) exhibit nucleotide sequence similarity with the other LHB/CGB genes, but as a result of frameshifting are predicted to encode a completely novel protein.In silico prediction of putative transcription factor binding sites supports the hypothesis that CGB1 and CGB2 gene products are expressed in, and may contribute to, implantation and placental development.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia.

ABSTRACT
The origin of completely novel proteins is a significant question in evolution. The luteinizing hormone (LHB)/chorionic gonadotropin (CGB) gene cluster in humans contains a candidate example of this process. Two genes in this cluster (CGB1 and CGB2) exhibit nucleotide sequence similarity with the other LHB/CGB genes, but as a result of frameshifting are predicted to encode a completely novel protein. Our analysis of these genes from humans and related primates indicates a recent origin in the lineage specific to humans and African great apes. While the function of these genes is not yet known, they are strongly conserved between human and chimpanzee and exhibit three-fold lower diversity than LHB across human populations with no mutations that would disrupt the coding sequence. The 5'-upstream region of CGB1/2 contains most of the promoter sequence of hCGbeta plus a novel region proximal to the putative transcription start site. In silico prediction of putative transcription factor binding sites supports the hypothesis that CGB1 and CGB2 gene products are expressed in, and may contribute to, implantation and placental development.

Show MeSH
Related in: MedlinePlus