Evolution and Organization of the Fibrinogen Locus on Chromosome 4: Gene Duplication Accompanied by Transposition and Inversion

Abstract

Human fibrinogen cDNA probes for the alpha-, beta-, and gamma-polypeptide chains have been used to isolate the corresponding genes from human genomic libraries. There is a single copy of each gene. Restriction endonuclease analysis of isolated genomic clones and human genomic DNA indicates that the human alpha-, beta-, and gamma-fibrinogen genes are closely linked in a 50-kilobase region of a single human chromosome: the alpha-gene in the middle flanked by the beta-gene on one side and the gamma-gene on the other. The alpha- and gamma-chain genes are oriented in tandem and transcribed toward the beta-chain gene. The beta-chain gene is transcribed from the opposite DNA strand toward the gamma- and alpha-chain genes. The three genes have been localized to the distal third of the long arm of chromosome 4, bands q23-q32, by in situ hybridization with fibrinogen cDNAs and by examination of DNA from multiple rodent-human somatic cell hybrids. Alternative explanations for the present arrangement of the three fibrinogen genes involve either a three-step mechanism with inversion of the alpha /gamma-region or a two-step mechanism involving remote transposition and inversion. The second more simple mechanism has a precedent in the origin of repeated regions of the fibrinogen and immunoglobulin genes.

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