High divergence in primate-specific duplicated regions: Human and chimpanzee Chorionic Gonadotropin Betagenes

Abstract

BackgroundLow nucleotide divergence between human and chimpanzee does not sufficiently explain the species-specific morphological, physiological and behavioral traits. As gene duplication is a major prerequisite for the emergence of new genes and novel biological processes, comparative studies of human and chimpanzee duplicated genes may assist in understanding the mechanisms behind primate evolution. We addressed the divergence between human and chimpanzee duplicated genomic regions by using Luteinizing Hormone Beta (LHB)/Chorionic Gonadotropin Beta (CGB) gene cluster as a model. The placental CGB genes that are essential for implantation have evolved from an ancestral pituitary LHB gene by duplications in the primate lineage.ResultsWe shotgun sequenced and compared the human (45,165 bp) and chimpanzee (39,876 bp) LHB/CGB regions and hereby present evidence for structural variation resulting in discordant number of CGB genes (6 in human, 5 in chimpanzee). The scenario of species-specific parallel duplications was supported (i) as the most parsimonious solution requiring the least rearrangement events to explain the interspecies structural differences; (ii) by the phylogenetic trees constructed with fragments of intergenic regions; (iii) by the sequence similarity calculations. Across the orthologous regions of LHB/CGB cluster, substitutions and indels contributed approximately equally to the interspecies divergence and the distribution of nucleotide identity was correlated with the regional repeat content. Intraspecies gene conversion may have shaped the LHB/CGB gene cluster. The substitution divergence (1.8–2.59%) exceeded two-three fold the estimates for single-copy loci and the fraction of transversional mutations was increased compared to the unique sequences (43% versus ~30%). Despite the high sequence identity among LHB/CGB genes, there are signs of functional differentiation among the gene copies. Estimates for dn/ds rate ratio suggested a purifying selection on LHB and CGB8, and a positive evolution of CGB1.ConclusionIf generalized, our data suggests that in addition to species-specific deletions and duplications, parallel duplication events may have contributed to genetic differences separating humans from their closest relatives. Compared to unique genomic segments, duplicated regions are characterized by high divergence promoted by intraspecies gene conversion and species-specific chromosomal rearrangements, including the alterations in gene copy number.

Expression and Production of Human Chorionic Gonadotropin (hCG) in the Normal Secretory Endometrium: Evidence of CGB7 and/or CGB6 Beta hCG Subunit Gene Expression1

“…The PCR procedure was performed immediately after reverse transcription in the same tube by adding 20 ll of PCR mixture as previously described [24]. Amplification of cDNA was performed using a common CGB gene primer pair to capture all of the specific CGB subunits expressed from CGB gene 3 (CGB3), gene 5, gene 6, gene 7, and gene 8 [3,[5][6][7] that should be expected to appear in amplicons of 548 and 378 bp as well as using a CGA primer pair [2] as demonstrated in Table 1 (CGB, CGB3, NM_000737.2; CGB5, NM_033043.1; CGB6, M13505.1, X00266; CGB7, NM_033142.1, M13503.1; CGB8, NM_033183.1; CGA, NM_000735). Additional genespecific CGB primer pairs were included to differentiate CGB5 from joint CGB7 and CGB6 gene expression.…”

“…All CGB genes are arranged in a gene cluster structure and are linked to a single highly homologous gene encoding the beta subunit of luteinizing hormone (LHB4). This CGB/ LHB gene cluster arose from the only ancestral LHB gene with segmental duplications, which is evolutionarily conserved and is only expressed in human and nonhuman primates [7]. With regard to evolution, the CGB7 and CGB6 subunits are described as the oldest phenotypic CGB variations, whereas the CGB5, CGB3, and CGB8 nucleotide structure variations comply with more recent gene locus development for hormone transcription and translation [8,9].…”

A novel two-promoter-one-gene system of the chorionic gonadotropin β gene enables tissue-specific expression

“…Interestingly, the putative novel exon 1 was found in all NWM analyzed but not other primate species. Despite the high-sequence homology among LHB/CGB genes (85-99%), there are signs of functional differentiation among the gene copies (Hallast et al 2008). It seems that in the NWM, the exon gains function during evolution, whereas in the OWM and humans no such function evolves.…”

Expression of Type II Chorionic Gonadotropin Genes Supports a Role in the Male Reproductive System

“…The chimpanzee LH/CG␤ cluster contains five CG␤ genes, rather than six as in humans, including two copies of CG␤1 and no CG␤2 (23). Gorilla, on the other hand, appears to have distinct CG␤1 and CG␤2 genes (22).…”

“…This substitution gave rise to the ancestor of the hCG␤1 gene, which was subsequently duplicated together with the adjacent hCG␤5 gene, to give hCG␤2 and hCG␤3 (Fig. 1A) (23). snaR-G1 and -G2 are located 86 bp upstream of the transcriptional start sites of hCG␤1 and -␤2, respectively, in the opposite orientation to the type II hCG␤ gene (44,46).…”