Human Chromosomes 3 and 21 are the products of an ancestral gene arrangement that is at least 300 million years old

There are seven known members of the class II cytokine receptor family: IFNAR1 and IFNAR2 (the two components of the a/b interferon receptors), IFNGR1 and IFNGR2 (the two components of the g interferon receptors), IL10R1 and IL10R2 (the two components of the interleukin-10 receptors), and the tissue factor gene, TF (Reboul et al. 1999). Four of these genes (IFNAR2, IL10R2, IFNAR1 and IFNGR2) cluster together on human Chromosome (Chr) 21 beside the GART gene (Schild et al. 1990), which is involved in purine biosynthesis. This gene, in fact, encodes a trifunctional protein with three enzyme activities: glycinamide ribonucleotide synthetase (GARS), aminoimidazole ribonucleotide synthetase (AIRS), and glycinamide ribonucleotide transformylase (GART) (Aimi et al. 1990). The fact that IFNAR2, IL10R2, IFNAR1,and IFNGR2are clustered together would indicate that these four genes are the most similar of the family members and produce the most structurally alike proteins (Gorman et al. 1992), suggesting these gene clusters are formed by gene duplication (Reboul et al. 1999). Three of these genes have also been studied in the chicken, being from the evolutionary-diverse avian lineage. They were found also to be clustered in the chicken, with the same gene order and direction of transcription. The relative spacing of the genes was also found to be conserved as was the intron/exon structure when compared with the human genes (Reboul et al. 1999). The arrangement of these genes was, therefore, fixed in the common ancestor, before the divergence of the two species, 300 million years ago. The map position of these genes has never been determined in chicken. The location of these genes in a non-mammalian species would be very interesting and helpful in determining whether synteny is conserved across the species. Analysis of the human and chicken GART gene also shows conservation of sequence and presumably function between the species (Aimi et al. 1990). A chicken 38-UTR probe was used to screen a lambda FIXII chicken genomic library. Four overlapping lambda clones were obtained; one of them was entirely sequenced (Accession number AF236855). As shown in Fig. 1a, it harbors two exons showing 100% identity with the GART cDNA sequence. According to the numbering of the exons on the murine GART gene (GenBank U20892) they correspond to exons 21 and 22. The corresponding gene was named GART-A. The genomic clone also harbors 12 exons for another gene encoding a protein highly similar to GART. This gene was, therefore, named GART-B; according to the murine numbering, exons 11 to 22 are present on the clone we have sequenced. GART-A and GART-B proteins are 66% identical over 650 a.a., and most differences are conservative. No significant conservation of sequence is observed between both genes outside the coding parts of the exons. The chicken GART gene, therefore, appears to be duplicated with both copies present tail to tail at the same locus. Three plasmids containing inserts from the lambda