A New Family of Predicted Krüppel-Like Factor Genes and Pseudogenes in Placental Mammals

Krüppel-like factors (KLF) and specificity proteins (SP) constitute a family of zinc-finger-containing transcription factors that play important roles in a wide range of processes including differentiation and development of various tissues. The human genome possesses 17 KLF genes (KLF1-KLF17) and nine SP genes (SP1-SP9) with diverse functions. We used sequence similarity searches and gene synteny analysis to identify a new putative KLF gene/pseudogene named KLF18 that is present in most of the placental mammals with sequenced genomes. KLF18 is a chromosomal neighbor of the KLF17 gene and is likely a product of its duplication. Phylogenetic analyses revealed that mammalian predicted KLF18 proteins and KLF17 proteins experienced elevated rates of evolution and are grouped with KLF1/KLF2/KLF4 and non-mammalian KLF17. Predicted KLF18 proteins maintain conserved features in the zinc fingers of the SP/KLF family, while possessing repeats of a unique sequence motif in their N-terminal regions. No expression data have been reported for KLF18, suggesting that it either has highly restricted expression patterns and specialized functions, or could have become a pseudogene in extant placental mammals. Besides KLF18 genes/pseudogenes, we identified several KLF18-like genes such as Zfp352, Zfp352-like, and Zfp353 in the genomes of mouse and rat. These KLF18-like genes do not possess introns inside their coding regions, and gene expression data indicate that some of them may function in early embryonic development. They represent further expansions of KLF members in the murine lineage, most likely resulted from several events of retrotransposition and local gene duplication starting from an ancient spliced mRNA of KLF18.