The Quiescin Q6 Gene (QSCN6) Is a Fusion of Two Ancient Gene Families: Thioredoxin and ERV1

Cell and tissue growth is a dynamic process determined by the fraction of cells in the proliferative cycle, the fraction of cells in quiescence, and the rate of cell death. Genes whose expression is induced at the beginning of the transition from the proliferative cell cycle to quiescence may play an important role in this process. We have identified a gene, Quiescin Q6 (QSCN6), whose expression is induced just as fibroblasts begin to leave the proliferative cycle and enter quiescence. QSCN6 is located on human chromosome 1q24, near the putative hereditary prostate cancer locus (HPC1). A triplet repeat (CTG)_nencodes a putative signal sequence. The gene encodes a 582-amino-acid open reading frame that has domains that are members of two ancient gene families. These domains apparently underwent a gene fusion event during metazoan evolution to create QSCN6. QSCN6 is most closely related to three genes of unknown function fromCaenorhabditis elegansas well as a gene from guinea pig. Analysis of this relationship showed nine Quiescin homology zones (QHZ). QHZ 0 is the putative signal sequence, QHZ 1 is homologous to a thioredoxin domain, and QHZ 2, 3, 4, and 8 are homologous only to themselves, while QHZ 5, 6, and 7 are homologous to the ERV1 gene ofSaccharomyces cerevisiae.In both thioredoxin and ERV1 gene superfamilies, QSCN6 sequences appear to be on distinct branches of their respective phylogenetic trees, consistent with an ancient origin of the QSCN6 gene. We present a model of the origin of QSCN6 and discuss its potential role in growth regulation.