An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons

• Published in: Nature (London) 2014-12, Vol.516 (7530), p.242-245
• Main Authors: Jacobs, Frank M. J., Greenberg, David, Nguyen, Ngan, Haeussler, Maximilian, Ewing, Adam D., Katzman, Sol, Paten, Benedict, Salama, Sofie R., Haussler, David
• Format: Article
• Language: English
• Subjects: 13/100; 631/181/735; 631/208/182; 631/208/726/2001/1428; 631/337/2569; Animals; Base Sequence; Embryonic Stem Cells - cytology; Embryonic Stem Cells - metabolism; Evolution, Molecular; Genetic research; Genetic transcription; Humanities and Social Sciences; Humans; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; letter; Mice; multidisciplinary; Mutation - genetics; Physiological aspects; Primates - genetics; Retroelements - genetics; Retrotransposons; Science; Zinc finger proteins; Zinc Fingers
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature13760

The authors show that two primate-specific genes encoding KRAB domain containing zinc finger proteins, ZNF91 and ZNF93, have evolved during the last 25 million years to repress retrotransposon families that emerged during this time period; according to the new data KZNF gene expansion limits the activity of newly emerged retrotransposons, which subsequently mutate to evade repression. The battle to repel DNA insertions Primate genomes have endured waves of retrotransposon insertions despite the host's attempts to prevent them and to block their transcription. KRAB domain containing zinc-finger proteins (KZNFs) plays a role in this transcriptional silencing in mouse embryonic stem cells. KZNFs are one of the fastest growing gene families in primates; this expansion has been hypothesized to enable primates to respond to newly emerged transposable elements. Here the authors provide evidence in support of this theory. They show that two primate-specific KZNF genes, ZNF91 and ZNF93 , have evolved during the past 25 million years to repress distinct retrotransposon families that emerged during this time period. According to the new data, KZNF gene expansion limits the activity of newly emerged retrotransposons, which subsequently mutate to evade repression. Throughout evolution primate genomes have been modified by waves of retrotransposon insertions 1 , 2 , 3 . For each wave, the host eventually finds a way to repress retrotransposon transcription and prevent further insertions. In mouse embryonic stem cells, transcriptional silencing of retrotransposons requires KAP1 (also known as TRIM28) and its repressive complex, which can be recruited to target sites by KRAB zinc-finger (KZNF) proteins such as murine-specific ZFP809 which binds to integrated murine leukaemia virus DNA elements and recruits KAP1 to repress them 4 , 5 . KZNF genes are one of the fastest growing gene families in primates and this expansion is hypothesized to enable primates to respond to newly emerged retrotransposons 6 , 7 . However, the identity of KZNF genes battling retrotransposons currently active in the human genome, such as SINE-VNTR-Alu (SVA) 8 and long interspersed nuclear element 1 (L1) 9 , is unknown. Here we show that two primate-specific KZNF genes rapidly evolved to repress these two distinct retrotransposon families shortly after they began to spread in our ancestral genome. ZNF91 underwent a series of structural changes 8–12 million years ago that enabled it to repress SVA e