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KRAB Zinc Finger Proteins coordinate across evolutionary time scales to battle retroelements

Jason D Fernandes, Maximilian Haeussler, Joel Armstrong, Kristof Tigyi, Joshua Gu, Natalie Filippi, Jessica Pierce, Tiffany Thisner, Paola Angulo, Sol Katzman, Benedict Paten, David Haussler, Sofie R Salama
doi: https://doi.org/10.1101/429563
Jason D Fernandes
1Genomics Institute, University of California, Santa Cruz
2Howard Hughes Medical Institute
3Department of Biomolecular Engineering, University of California, Santa Cruz
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Maximilian Haeussler
1Genomics Institute, University of California, Santa Cruz
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Joel Armstrong
1Genomics Institute, University of California, Santa Cruz
3Department of Biomolecular Engineering, University of California, Santa Cruz
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Kristof Tigyi
1Genomics Institute, University of California, Santa Cruz
2Howard Hughes Medical Institute
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Joshua Gu
1Genomics Institute, University of California, Santa Cruz
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Natalie Filippi
1Genomics Institute, University of California, Santa Cruz
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Jessica Pierce
1Genomics Institute, University of California, Santa Cruz
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Tiffany Thisner
4Big Data to Knowledge Program, California State University, Monterey Bay
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Paola Angulo
1Genomics Institute, University of California, Santa Cruz
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Sol Katzman
1Genomics Institute, University of California, Santa Cruz
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Benedict Paten
1Genomics Institute, University of California, Santa Cruz
3Department of Biomolecular Engineering, University of California, Santa Cruz
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David Haussler
1Genomics Institute, University of California, Santa Cruz
2Howard Hughes Medical Institute
3Department of Biomolecular Engineering, University of California, Santa Cruz
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  • For correspondence: haussler@ucsc.edu salama@ucsc.edu
Sofie R Salama
1Genomics Institute, University of California, Santa Cruz
2Howard Hughes Medical Institute
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  • For correspondence: haussler@ucsc.edu salama@ucsc.edu
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Abstract

KRAB Zinc Finger Proteins (KZNFs) are the largest and fastest evolving family of human transcription factors1,2. The evolution of this protein family is closely linked to the tempo of retrotransposable element (RTE) invasions, with specific KZNF family members demonstrated to transcriptionally repress specific families of RTEs3,4. The competing selective pressures between RTEs and the KZNFs results in evolutionary arms races whereby KZNFs evolve to recognize RTEs, while RTEs evolve to escape KZNF recognition5. Evolutionary analyses of the primate-specific RTE family L1PA and two of its KZNF binders, ZNF93 and ZNF649, reveal specific nucleotide and amino changes consistent with an arms race scenario. Our results suggest a model whereby ZNF649 and ZNF93 worked together to target independent motifs within the L1PA RTE lineage. L1PA elements eventually escaped the concerted action of this KZNF “team” over ∼30 million years through two distinct mechanisms: a slow accumulation of point mutations in the ZNF649 binding site and a rapid, massive deletion of the entire ZNF93 binding site.

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  • ↵# Co-senior author

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Posted September 27, 2018.
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KRAB Zinc Finger Proteins coordinate across evolutionary time scales to battle retroelements
Jason D Fernandes, Maximilian Haeussler, Joel Armstrong, Kristof Tigyi, Joshua Gu, Natalie Filippi, Jessica Pierce, Tiffany Thisner, Paola Angulo, Sol Katzman, Benedict Paten, David Haussler, Sofie R Salama
bioRxiv 429563; doi: https://doi.org/10.1101/429563
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KRAB Zinc Finger Proteins coordinate across evolutionary time scales to battle retroelements
Jason D Fernandes, Maximilian Haeussler, Joel Armstrong, Kristof Tigyi, Joshua Gu, Natalie Filippi, Jessica Pierce, Tiffany Thisner, Paola Angulo, Sol Katzman, Benedict Paten, David Haussler, Sofie R Salama
bioRxiv 429563; doi: https://doi.org/10.1101/429563

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