An unidentified gene product, YGHL1  has been isolated from yellowtail pituitary in our laboratory in 1996 (DDBJ: D85880).  In the present study, its cDNA, genomic organization, and expression in different organs were studied for the first time in lower vertebrates, and the genomic organization was compared between human and yellowtail.  The full length cDNA of YGHL1 was 1529 bp long with coding sequence for a 92 amino acid polypeptide with homology to the recently reported hypoxia induced gene 1 in a fish, Gillichtys (HIG1) and mouse (Hig1). Northern blot analysis of YGHL1 showed that the mRNA was expressed in brain, gill, heart, and kidney in yellowtail.  Especially high expression was observed in brain and heart, suggesting YGHL1 may have a special role in these organs.  No expression of YGHL1 was observed in liver and skeletal muscle under  normal conditions as reported with HIG1 in Gillitchys liver.  A genomic region spanning 6800 bp for YGHL1 was  sequenced, and the YGHL1 mRNA was encoded by 4 exons and 3 introns spanning 2416 bp of genomic DNA (AB094665). No hypoxia responsive element (HRE) as predicted by the other workers was found in the genomic region, but CRE/CREB cAMP responsive elements were located at -20 of the start of transcription.  This genomic feature was virtually identical with the human HIG1 in 3p21.32, except cAMP responsive elements, ATF-CREB/CRE-BP were located upstream of human HIG1. CLST11240,  mapping to human 17q21.39 was identified as a HIG1 paralog.   This gene was less homologous to YGHL1 than HIG1, but a virtually identical genomic organization was observed, except CLST11240 lacked the first, non-coding, exon.  Forty-six amino acid residues encoded by the exon 3 in YGHL1 showed the highest conservation, and at least 4 functional paralogs were identified in mammalian genomes, including human.  In addition, at least YGHL1 10 pseudogene loci were identified in the human genome and 5 of them were intronless, retrotransposed loci. We also identified  orthologous genes to YGHL1 in Xenopus leavis, fruit fly and a mosquito, and similar genomic organizations were retained, as well as their putatively encoded polypeptides. We also identified YGHL1 homologs in yeasts and a more conserved locus in Arabidopsis. YGHL1, HIG1, CLST11240 and DKFZP564K247 appeared to be generated early in the evolution of vertebrates 450 mya ago from a very old ancestral gene present at least 1000 mya ago.