Evolution and organization of the fibrinogen locus on chromosome 4: gene duplication accompanied by transposition and inversion.

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Abstract
Human fibrinogen cDNA [complementary DNA] probes for the .alpha.-, .beta.- and .gamma.-polypeptide chains were 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 3 genes were localized to the distal 3rd of the long arm of chromosome 4, bands q23-q32, by in situ hybridization with fibrinogen cDNA and by examination of DNA from multiple rodent-human somatic cell hybrids. Alternative explanations of the present arrangement of the 3 fibrinogen genes involve either a 3-step mechanism with inversion of the .alpha./.gamma.-region or a 2-step mechanism involving remote transposition and inversion. The 2nd more simple mechanism has a precedent in the origin of repeated regions of the fibrinogen and Ig genes.