Molecular characterization of STAT5A-and STAT5B-encoding genes reveals extended intragenic sequence homogeneity in cattle and mouse and different degrees of divergent evolution of various domains

The STAT transcription factors form a family of signal transducers and acti vators of transcription. We sequenced the bovine STAT5B cDNA and both STAT5 -encoding genes, STAT5A and STAT5B, representing the first complete descrip tion of any STAT5-encoding gene. DNA fiber FISH hybridization revealed that the genes reside only 40 kbp apart on BTA19, Both genes are segmented into 19 exons and all but two of the homologous exons are of equal size. The ge nes harbor a central block of nearly identical DNA sequence (97.5% sequence identity over 3373 bp), spanning from intron 5 to intron 9. Isolation and sequencing of the homologous segments from mouse revealed the same unusuall y high degree of intronic sequence conservation in these segments of the mu rine STAT5-encoding genes. However, the respective sequences are completely divergent between the two species. A comparison of the inter- and intragen ic cDNA sequence preservation at nonsynonymous sites reveals that the DNA-b inding domain is under the strongest selection pressure for both intergenic and factor-specific intragenic sequence preservation. The so-called "SH3" segment of the linker domain, in contrast, shows species-specific sequence identity in all but one amino acid residues in both factors, in cattle, hum an, and mouse. This indicates that the same species-specific selection pres sure occurs on the linker domain from both factors, STAT5A and STAT5B. Thus , the comparison of evolutionary selection pressures resting on various dom ains suggests that the DNA-binding domain might contribute to differential DNA binding of STAT5A and STAT5B factors, while both might interact equally well with other cellular factors through a segment of the linker domain.