Structure, evolution and chromosomal localization of the human pregnancy-specific beta 1 glycoprotein gene family

Cloning and sequencing of the cDNA of a new member of the PS beta G gene family is reported. Comparison of the sequence with those of other PS beta G cDNAs reveals a remarkable conservation of their sequence (greater than 90%) and of their general structural organization: an NH2 domain is followed by 93- and 85-residue Ig-like domains termed A and B, respectively. Most PS beta G contain two domains A in tandem followed by a single domain B. In some PS beta G members described here, alternative splicing skips the AI domain in some transcripts, yielding two- and three-domain variants, respectively. Individual PS beta G members have specific short carboxyl domains displaying little sequence conservation. The PS beta G family is closely related to the CEA gene family. A detailed comparison of the sequence of both families is given and used to construct an evolutionary tree, using the method of Li, Wu, and Luo (1985, Mol. Biol. Evol. 2: 150-174). Computation of the number of substitutions of synonymous (Ks) and nonsynonymous (Ka) sites and of the Ks/Ka ratio suggests that the PS beta G gene family appeared concomitantly with the expansion of the placental mammals and belongs to the class of rapidly evolving genes. Very little selective pressure has been exerted on the body of the molecules, especially on domain A. The analysis also suggests that PS beta G genes encoding different carboxyl domains would have been positively selected and fixed during the evolution. The PS beta G gene family was assigned to chromosome 19, which also carries the CEA genes.