The Distal-Proximal Relationships Among the Human Moonlighting Proteins: Evolutionary hotspots and Darwinian checkpoints

Abstract

Moonlighting proteins, known for their ability to perform multiple, often unrelated functions within a single polypeptide chain, challenge the traditional "one gene, one protein, one function" paradigm. As organisms evolved, their genomes remained relatively stable in size, but the introduction of post-translational modifications and sub-strategies like protein promiscuity and intrinsic disorder enabled multifunctionality. Enzymes, in particular, exemplify this phenomenon, engaging in unrelated processes alongside their primary catalytic roles. This study employs a systematic, quantitative informatics approach to shed light on human moonlighting protein sequences. Phylogenetic analyses of human moonlighting proteins are presented, elucidating the distal-proximal relationships among these proteins based on sequence-derived quantitative features. The findings unveil the captivating world of human moonlighting proteins, urging further investigations in the emerging field of moonlighting proteomics, with the potential for significant contributions to our understanding of multifunctional proteins and their roles in diverse cellular processes and diseases.

Molecular Genomic Insights into Melanoma Associated Proteins PRAME and BAP1

“…A homogeneous poly-string of length n is characterized as a sequence consisting of n consecutive instances of a specific amino acid, as defined by Nawn et al [32]. For example, in the sequence ‘KKKLLKKLL’, we can identify one homogeneous poly-string of K with a length of 3, one with a length of 2, and two homogeneous poly-strings of L with a length of 2.…”

“…Subsequently, the protein sequence underwent transformation into a binary sequence using two symbols: P and Q. This binary P-Q profile served the purpose of representing the spatial arrangement of polar and non-polar residues within the protein sequence [32, 33, 34].…”

“…There are four possible transitions between two consecutive residues in a polar and non-polar profile: Polar to Polar (PP), Polar to Non-polar (PN), Non-polar to Non-polar (NN), and Non-polar to Polar (NP), as outlined in the study by Nawn et al [32]. These transitions were documented in the form of a sequence, considering the sequential spatial arrangement of polar and non-polar residues within a given P-Q binary profile.…”

“…These transitions were documented in the form of a sequence, considering the sequential spatial arrangement of acidic, basic, and neutral residues within a given A-B-N ternary profile. This sequence is referred to as the “A-B-N Change Response Sequence ( CRS ABN )” [32].…”

“…These transitions were documented in the form of a sequence, considering the sequential spatial arrangement of D, HF, MF, and O residues within each sequence. This sequence is referred to as the “Change Response Sequence,” and the frequency of each of the sixteen changes was tabulated from these sequences, as outlined in the work by Nawn et al [32].…”