TANDEM ARRANGEMENT OF THE HUMAN SERUM-ALBUMIN MULTIGENE FAMILY IN THESUB-CENTROMERIC REGION OF 4Q - EVOLUTION AND CHROMOSOMAL DIRECTION OFTRANSCRIPTION

The albumin gene family is comprised of four genes encoding: serum alb umin (ALB), alpha-fetoprotein (AFP), alpha-albumin (ALF), and vitamin D-binding protein (DBP; also known as GC). The genes are regulated dev elopmentally, expressed in the Liver, and the proteins are secreted in to the bloodstream. The GC gene, and the tandemly Linked ALE and AFP g enes, have been previously localized to human chromosome 4q11-13. Usin g techniques of fluorescence in situ hybridization to chromatin fibres , chromosome walking and DNA sequencing of genomic clones, we now repo rt on the chromosomal location of the ALF gene and the organization of the entire gene family The four genes are tandemly linked in the 4q s ub-centromeric region: 5'ALB-5'AFP-5'ALF-5'GC3'-centromere, and hence are transcribed in the same, centromere-bound, direction. The linear a rrangement of the four genes along the chromosome is not correlated wi th their temporal expression in the human ontogeny. It appears that GC is wry close (and may be the gene proximal) to the centromere. The li near chromosomal arrangement of the four genes and the structural diff erences between them are congruent with the following evolutionary div ergence of the gene family Starting with the first duplication of an a ncestral progenitor gene, a single evolutionary line led to the contem porary GC, leaving ALB/AFP/ALF on the other line of descent. The secon d duplication occurred in this ALE lineage, giving rise to ALE and the AFP/ALF progenitor, and the third, most recent one, gave rise to the AFP-ALF pair. (C) 1996 Academic Press Limited.