Evolution of the Chorionic Gonadotropin β Genes in Primates

Abstract

Several genes associated with reproduction have been duplicated during primate evolution and evolved under positive selection. Chorionic gonadotropin hormone (HCG) produced by trophoblast cells has emerged in primates and assists maternal physiology to establish pregnancy. CGB gene, coding for the HCG β subunit has evolved through a duplication of the ancestral lutenizing hormone β ( LHB ) gene 55–35 million years ago. Only a few sequence changes in the duplicate locus were required to result in a novel CGB gene with different tissue‐specificity and function. Evolution of the LHB / CGB genomic region has been accompanied by active genome dynamics either as series of additional duplications in Old World monkeys and apes, or as functional modifications of genes in New World monkeys. Duplicated, highly homologous genes with diverged functions are maintained through a balance between selective pressures targeted to their specific functions and evolution in consort facilitated by interlocus gene conversion. Key Concepts Several genes associated with female and male reproduction have been shown to be duplicated during primate evolution and evolve under positive selection. Chorionic gonadotropin hormone (HCG) produced by the trophoblast cells has emerged in primates and acts as a key hormone to assist maternal physiology to establish pregnancy. Primate‐specific CGB gene, coding for the β subunit of HCG has emerged through a duplication of the ancestral lutenizing hormone β ( LHB ) gene approximately 55–35 million years ago. Only a few sequence changes in the duplicate locus were required to result in a novel CGB gene with different tissue‐specificity, expression pattern and function. Evolution of the LHB / CGB genomic region in primates has been accompanied by active genome dynamics either as a series of additional duplications in the lineage to OWM and apes, or as functional modifications of the gene loci in NWM. Comparison of the human and chimpanzee LHB/CGB gene clusters identified large species‐specific parallel rearrangement events, resulting in lineage‐specific number of CGB gene copies (five versus six genes in chimpanzee compared to human). Duplicated genes tend to evolve in consort facilitated by active interlocus gene conversion increasing and preserving sequence similarity among the gene copies. Intraspecies gene conversion events have led to a higher human–chimpanzee divergence between duplicated LHB/CGB genes compared to the available data for unique genomic regions. Duplicated, highly homologous genes with diverged functions are maintained through balancing interlocus gene conversion activity with selective pressure targeting their specific functions.

Unconventional Actions of Glycoprotein Hormone Subunits: A Comprehensive Review

“…In addition to the two pituitary gonadotropins and TSH that are present in all vertebrate branches, an additional heterodimeric gonadotropin is produced in primates ( 1 ) and in equids ( 52 ) mainly by the placenta. In primates, the locus encompassing lhb has been submitted to serial tandem duplication events giving rise to 6 functional lhb -derived genes in human ( 53 – 55 ). Most of them are essentially expressed, together with the GPHα subunit, by syncytiotrophoblastic cells in the placenta to produce the chorionic gonadotropin (CG).…”

Genomics and genetics of gonadotropin beta-subunit genes: Unique FSHB and duplicated LHB/CGB loci

“…Functionally divergent CGB probably emerged from a duplicate LHB gene copy in the common ancestor of anthropoid primates 55–35 million years ago and it demonstrates an excellent example of the power of evolution by gene duplication ( Ohno, 1970 ). After the initial gene duplication event, the evolution of the LHB / CGB gene cluster in New World monkeys ( Platyrrhini ) compared to Old World monkeys, apes and humans ( Catarrhini ) have followed different scenarios (reviewed in detail in Henke and Gromoll, 2008; Hallast and Laan, 2009 ). All the New World monkey species studied so far (e.g.…”

“…The high sequence similarity among the genes (up to 99%) as well as inter-genic regions (up to 97%) of the human LHB / CGB gene cluster provides an ideal surface for the gene conversion activity. Due to the homogenizing effect of gene conversion events, the intra-specific LHB / CGB genes have become more closely related to each other than to their counterparts in closely related species ( Maston and Ruvolo, 2002; Hallast and Laan, 2009 ). The observed transferred sequence tracts between the LHB / CGB genes have been determined to range from a few bp to maximum 796 bp ( Hallast et al, 2005 ).…”

“…The black boxes and arrowheads indicate CGB , white LHB and grey neighbouring genes. The CGB genes of rhesus macaque ( Macaca mulatta ) and common marmoset ( Callithrix jacchus ) are indicated as CGB A – C , since their ancestral status relative to the human CGB genes is unknown (reviewed in Henke and Gromoll, 2008; Hallast and Laan, 2009 ).…”

“…Loci for FSH beta (denoted FSHB in primates, Fshb in mammals and GTH-I in fishes) and LH beta (denoted LHB in primates, Lhb in mammals and GTH-II in fishes) are conserved among vertebrates and functional genes have been cloned in fishes, amphibians, reptiles, birds and mammals ( Gharib et al, 1989; Guzman et al, 1991; Kumar et al, 1995; Rosenfeld et al, 2001; Shen and Yu, 2002; Kawasaki et al, 2003; Watanabe et al, 2007 ). The beta-subunit of CG ( CGB ) probably emerged from a duplicate LHB gene copy approximately 55–35 million years ago before the divergence of New World and Old World monkeys ( Talmadge et al, 1984; Policastro et al, 1986; Bailey et al, 1991; Maston and Ruvolo, 2002 ; reviewed in Henke and Gromoll, 2008; Hallast and Laan, 2009 ). Only a few sequence changes led to the novel function and different expression pattern of the derived CGB gene compared to the ancestral LHB ( Fiddes and Goodman, 1980; Talmadge et al, 1984 ).…”