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.

类Krüppel因子（Krüppel-like factors, KLF）与特异性蛋白（specificity proteins, SP）共同构成一类含锌指结构的转录因子（zinc-finger-containing transcription factors）家族，在多种组织的分化与发育等广泛生物学过程中发挥重要作用。人类基因组共拥有17种KLF基因（KLF1–KLF17）与9种SP基因（SP1–SP9），功能各异。本研究通过序列相似性搜索与基因同线性分析（gene synteny analysis），鉴定出一个新的推定KLF基因/假基因（pseudogene），命名为KLF18，该基因存在于绝大多数已完成基因组测序的胎盘哺乳动物中。KLF18位于KLF17基因的染色体邻位区域，极有可能由KLF17基因复制产生。系统发育分析（phylogenetic analyses）结果显示，哺乳动物来源的预测KLF18蛋白与KLF17蛋白的进化速率均有所升高，且与KLF1/KLF2/KLF4以及非哺乳动物KLF17共同聚类。预测的KLF18蛋白保留了SP/KLF家族锌指结构的保守特征，但其N端区域存在独特序列基序（sequence motif）的重复序列。目前尚无KLF18的相关表达数据，这提示其要么表达模式高度受限且功能特化，要么在现存胎盘哺乳动物中已演变为假基因。除KLF18基因/假基因外，本研究还在小鼠与大鼠的基因组中鉴定出数个KLF18样基因，包括Zfp352、Zfp352-like及Zfp353。这类KLF18样基因的编码区内不含内含子（intron），结合基因表达数据可知，其中部分基因可能在早期胚胎发育过程中行使功能。它们是鼠类谱系中KLF家族成员的进一步扩张，大概率起源于以KLF18的古老剪接mRNA为起始模板的数次逆转座（retrotransposition）与局部基因复制事件。