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

2018 ◽  
Author(s):  
Jason D Fernandes ◽  
Maximilian Haeussler ◽  
Joel Armstrong ◽  
Kristof Tigyi ◽  
Joshua Gu ◽  
...  
Keyword(s):  
Binding Site ◽  
Zinc Finger ◽  
Point Mutations ◽  
Zinc Finger Proteins ◽  
Arms Race ◽  
Concerted Action ◽  
Evolutionary Time ◽  
Arms Races ◽  
Selective Pressures ◽  
Retrotransposable Element

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.

scholarly journals Endless Conflicts: Detecting Molecular Arms Races in Mammalian Genomes

2019 ◽  
Author(s):  
Jacob C. Cooper ◽  
Christopher J. Leonard ◽  
Brent S. Pedersen ◽  
Clayton M. Carey ◽  
Aaron R. Quinlan ◽  
...  
Keyword(s):  
Positive Selection ◽  
Phylogenetic Group ◽  
Arms Race ◽  
Deer Mice ◽  
Polymeric Immunoglobulin Receptor ◽  
Arms Races ◽  
Immunoglobulin Receptor ◽  
Selective Pressures ◽  
Gene Level ◽  
Mammalian Genomes

AbstractRecurrent positive selection at the codon level is often a sign that a gene is engaged in a molecular arms race – a conflict between the genome of its host and the genome of another species over mutually exclusive access to a resource that has a direct effect on the fitness of both individuals. Detecting molecular arms races has led to a better understanding of how evolution changes the molecular interfaces of proteins when organisms compete over time, especially in the realm of host-pathogen interactions. Here, we present a method for detection of gene-level recurrent positive selection across entire genomes for a given phylogenetic group. We deploy this method on five mammalian clades – primates, mice, deer mice, dogs, and bats – to both detect novel instances of recurrent positive selection and to compare the prevalence of recurrent positive selection between clades. We analyze the frequency at which individual genes are targets of recurrent positive selection in multiple clades. We find that coincidence of selection occurs far more frequently than expected by chance, indicating that all clades experience shared selective pressures. Additionally, we highlight Polymeric Immunoglobulin Receptor (PIGR) as a gene which shares specific amino acids under recurrent positive selection in multiple clades, indicating that it has been locked in a molecular arms race for ∼100My. These data provide an in-depth comparison of recurrent positive selection across the mammalian phylogeny, and highlights of the power of comparative evolutionary approaches to generate specific hypotheses about the molecular interactions of rapidly evolving genes.

The Arms Race Between KRAB–Zinc Finger Proteins and Endogenous Retroelements and Its Impact on Mammals

2019 ◽  
Vol 53 (1) ◽  
pp. 393-416 ◽  
Author(s):  
Melania Bruno ◽  
Mohamed Mahgoub ◽  
Todd S. Macfarlan
Keyword(s):  
Transcription Factors ◽  
Structure Function ◽  
Human Genome ◽  
Zinc Finger ◽  
Driving Force ◽  
Zinc Finger Proteins ◽  
Arms Race ◽  
Host Genome ◽  
Current Understanding ◽  
Genome Integrity

Nearly half of the human genome consists of endogenous retroelements (EREs) and their genetic remnants, a small fraction of which carry the potential to propagate in the host genome, posing a threat to genome integrity and cell/organismal survival. The largest family of transcription factors in tetrapods, the Krüppel-associated box domain zinc finger proteins (KRAB-ZFPs), binds to specific EREs and represses their transcription. Since their first appearance over 400 million years ago, KRAB-ZFPs have undergone dramatic expansion and diversification in mammals, correlating with the invasions of new EREs. In this article we review our current understanding of the structure, function, and evolution of KRAB-ZFPs and discuss growing evidence that the arms race between KRAB-ZFPs and the EREs they target is a major driving force for the evolution of new traits in mammals, often accompanied by domestication of EREs themselves.

scholarly journals Transcription of alpha-specific genes in Saccharomyces cerevisiae: DNA sequence requirements for activity of the coregulator alpha 1.

1993 ◽  
Vol 13 (11) ◽  
pp. 6866-6875 ◽  
Author(s):  
D C Hagen ◽  
L Bruhn ◽  
C A Westby ◽  
G F Sprague
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Binding Site ◽  
Dna Sequences ◽  
Point Mutations ◽  
Transcription Activation ◽  
Specific Gene ◽  
Binding Assays ◽  
Weak Binding

Transcription activation of alpha-specific genes in Saccharomyces cerevisiae is regulated by two proteins, MCM1 and alpha 1, which bind to DNA sequences, called P'Q elements, found upstream of alpha-specific genes. Neither MCM1 nor alpha 1 alone binds efficiently to P'Q elements. Together, however, they bind cooperatively in a manner that requires both the P' sequence, which is a weak binding site for MCM1, and the Q sequence, which has been postulated to be the binding site for alpha 1. We analyzed a collection of point mutations in the P'Q element of the STE3 gene to determine the importance of individual base pairs for alpha-specific gene transcription. Within the 10-bp conserved Q sequence, mutations at only three positions strongly affected transcription activation in vivo. These same mutations did not affect the weak binding to P'Q displayed by MCM1 alone. In vitro DNA binding assays showed a direct correlation between the ability of the mutant sequences to form ternary P'Q-MCM1-alpha 1 complexes and the degree to which transcription was activated in vivo. Thus, the ability of alpha 1 and MCM1 to bind cooperatively to P'Q elements is critical for activation of alpha-specific genes. In all natural alpha-specific genes the Q sequence is adjacent to the degenerate side of P'. To test the significance of this geometry, we created several novel juxtapositions of P, P', and Q sequences. When the Q sequence was opposite the degenerate side, the composite QP' element was inactive as a promoter element in vivo and unable to form stable ternary QP'-MCM1-alpha 1 complexes in vitro. We also found that addition of a Q sequence to a strong MCM1 binding site allows the addition of alpha 1 to the complex. This finding, together with the observation that Q-element point mutations affected ternary complex formation but not the weak binding of MCM1 alone, supports the idea that the Q sequence serves as a binding site for alpha 1.

scholarly journals Engineering Zinc Finger Proteins using Accessory Binding Modules

2012 ◽  
Vol 102 (3) ◽  
pp. 74a
Author(s):  
Kathryn Trenshaw ◽  
Younghoon Kim ◽  
Nathan Yee ◽  
Peiyi Wang ◽  
Charles Schroeder
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Proteins
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