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Explore the fascinating world of protein domains, DNA motifs, and miRNA targets, delving into the intricacies of post-translational modifications like "skittle-izing" motifs and the unique functions of proteins like ZNF136. Discover how promiscuous domains challenge traditional evolutionary narratives.
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Exploring Promiscuous Protein Domains and DNA/Protein Motifs through Pedagogy and PracticePart 1 Salvador Cordova
“Write” operations are one kind of Post Translational Modification (PTM) of proteins
Exploring Promiscuous Protein Domains and DNA/Protein Motifs through Pedagogy and PracticePart 1 Salvador Cordova
Collagens account for around 25% of the protein mass in our bodies!
FASTA sequence of Collagen Type 1, Alpha 1 paralog (1464 aa)
Skittle-izingG-X-X motif (Seaman-Sanford DNA skittle) non-Random Pattern, Violation of Law of Large Numbers
Important Motif in Collagen • G X X • echoes Kleene Regular Expressions and Backus Naur forms of computer science and formal languages
Protein Motifs DNA Motifs miRNA targets repetitive elements Protein Domains binding motifs
A protein domain is any identifiable subsequence of a protein that can fold, function and exist independently of the rest of the protein chain or structure. Annotating New Genes From in Silico Screening to Experimental Validation Woodhead Publishing Series in Biomedicine 2012, Pages 7-47 “Protein domain is a definable component of a protein. Domains are somewhat quantized entities.”
Protein Motifs DNA Motifs miRNA targets repetitive elements Protein Domains binding motifs
Promiscuous domains and motifs are domains and motifs that appear in several proteins/genes in a way not explainable by universal common descent Protein Motifs miRNA targets repetitive elements Protein Domains binding motifs
Classical C2H2 Zinc Finger Motif/Domain in ZNF136 radically different function than collagen lots of machines have to be in place for KRAB-Zinc Finger Proteins to be functionally integrated
Looking Ahead Problems of Common Descent Gradual transitionals from common ancestor infeasible because of the scarcity or absence of integrated functional intermediates!
Machines With Similar Conceptual ArchitecturesDifferent Implementations
Each line is a valid C2H2 Zinc Finger Domain/Motif
Each line is a valid C2H2 Zinc Finger Domain/Motif
Each line is a valid C2H2 Zinc Finger Domain/Motif
Other Kinds of Zinc Fingers (non-classical) RING Finger Zinc Finger (Really Interesting New Gene)
ZNF136 Sequence Each line is a valid C2H2 zinc finger domain
ZNF136 Sequence Each line is a valid C2H2 zinc finger domain
ZNF136 Sequence 1 KRAB-A domain, 13 C2H2 Classical Zinc Finger Domains KRAB-A domain Each line is a valid C2H2 zinc finger domain
KRAB-A Domain SVAFEDVDVNFTQEEWALLDPSQKNLYRDVMWETMRNLASIG
ZNF136 Sequence KRAB A domain Each line is a valid C2H2 zinc finger domain
Differences in zinc finger sequences are functionally important! Much like notches, slots, and grooves in a key! Even though keys share common architecture.
Can zinc fingers domains in a zinc finger protein be explained by a series of random duplications and random point mutations from a single ancestral zinc finger? I say: NO!
Evolutionary biologists might argue “yes”, because they can build hierarchical diagrams and claim this describes the phylogenetic evolutionary relationship from an ancestral zinc finger
Is this “phylogeny” a valid reconstruction of history? • Emphatic “NO” as a matter of principle -- my opinion
ZNF136 Sequence KRAB A domain Each line is a valid C2H2 zinc finger domain