A COMPREHENSIVE EVOLUTIONARY ANALYSIS BASED ON NUCLEOTIDE AND AMINO-ACID-SEQUENCES OF THE ALPHA-SUBUNIT AND BETA-SUBUNIT OF GLYCOPROTEIN HORMONE GENE FAMILY

On the basis of nucleotide sequences of the coding region and their pr edicted amino acid sequences, 58 glycoprotein hormone subunit genes we re compared, aligned and used to construct phylogenetic trees for this family. The analysis included 17 alpha-subunits, eight TSH beta-, six FSH beta-, 17 LH beta/CG beta-, four fish gonadotropin (GTH)-I beta-, five fish GTH-II beta- and one additional fish GTH beta-subunits. The reliability of the phylogenetic trees was probed with the bootstrappi ng test. Our results indicated that: both the alpha- and beta-subunits of the family diverged from a common ancestral gene about 927 million years ago; the initial precursor of the beta-subunit duplicated to gi ve rise to the LH beta and a second hormone, the latter then duplicati ng to FSH beta and TSH beta, so that FSH beta is related more to TSH b eta than to LH beta; and bony fish GTH-I beta is highly related to mam malian FSH beta, whereas the bony fish GTH-II beta is more related to mammalian LH beta. For scientific consistency and convenience, we prop ose that the following nomenclature be adopted; all fish gonadotropins of type I be classified as FSH and all type II be classified as LH ho rmones, In addition, on the basis of results from this and other studi es, we propose an evolutionary history for this glycoprotein hormone f amily. Reconstruction of the evolutionary history of this family would not only provide clues to understanding thyrotropin and gonadotropin functions, but would also allow further revision of the present nomenc lature of the gonadotropins in fish.