THE CHICKEN GENOME CONTAINS 2 FUNCTIONAL NONALLELIC BETA-1,4-GALACTOSYLTRANSFERASE GENES - CHROMOSOMAL ASSIGNMENT TO SYNTENIC REGIONS TRACKS FATE OF THE 2 GENE LINEAGES IN THE HUMAN GENOME

Two distinct but related groups of cDNA clones, CK beta 4GT-I and CK b eta 4GT-II, have been isolated by screening a chicken hepatoma cDNA li brary with a bovine beta 1,4-galactosyltransferase (beta 4GT) cDNA clo ne, CK beta 4GT-I is predicted to encode a type II transmembrane glyco protein of 41 kDa with one consensus site for N-linked glycosylation, CK beta 4GT-II is predicted to encode a type II transmembrane glycopro tein of 43 kDa with five potential N-linked glycosylation sites, At th e amino acid level, the coding regions of CK beta 4GT-I and CK beta 4G T-II are 52% identical to each other and 62 and 49% identical, respect ively, to bovine beta 4GT, Despite this divergence in amino acid seque nce, high levels of expression of each cDNA in Trichoplusia ni insect cells demonstrate that both CK beta 4GT-I and CK beta 4GT-II encode an alpha-lactalbumin-responsive, UDP-galactose:N-acetylglucosamine beta 4-galactosyltransferase. An analysis of CK beta 4GT-I and CK beta 4GT- II, genomic clones established that the intron positions within the co ding region are conserved when compared with each other, and these pos itions are identical to the mouse and human beta 4GT genes. Thus CK be ta 4GT-I and CK beta 4GT-II are the result of the duplication of an an cestral gene and subsequent divergence, CK beta 4GT-I maps to chicken chromosome Z in a region of conserved synteny with the centromeric reg ion of mouse chromosome 4 and human chromosome 9p, where beta 4-galact osyltransferase (EC 2.4.1.38) had previously been mapped, Consequently , during the evolution of mammals, it is the CK beta 4GT-I gene lineag e that has been recruited for the biosynthesis of lactose, CK beta 4GT -II maps to a region of chicken chromosome 8 that exhibits conserved s ynteny with human chromosome Ip, An inspection of the current human ge ne map of expressed sequence tags reveals that there is a gene noted t o be highly similar to beta 4GT located in this syntenic region on hum an chromosome Ip, Because both the CK beta 4GT-I and CK beta 4GT-II ge ne lineages are detectable in mammals, duplication of the ancestral be ta 4-galactosyltransferase gene occurred over 250 million years ago in an ancestral species common to both mammals and birds.