Abstract
We have developed the program TwinCons, to detect noisy signals of deep ancestry of proteins or nucleic acids. As input, the program uses a composite alignment containing pre-defined groups, and mathematically determines a 'cost' of transforming one group to the other at each position of the alignment. The output distinguishes conserved, variable and signature positions. A signature is conserved within groups but differs between groups. The method automatically detects continuous characteristic stretches (segments) within alignments. TwinCons provides a convenient representation of conserved, variable and signature positions as a single score, enabling the structural mapping and visualization of these characteristics. Structure is more conserved than sequence. TwinCons highlights alternative sequences of conserved structures. Using TwinCons, we detected highly similar segments between proteins from the translation and transcription systems. TwinCons detects conserved residues within regions of high functional importance for the ribosomal RNA (rRNA) and demonstrates that signatures are not confined to specific regions but are distributed across the rRNA structure. The ability to evaluate both nucleic acid and protein alignments allows TwinCons to be used in combined sequence and structural analysis of signatures and conservation in rRNA and in ribosomal proteins (rProteins). TwinCons detects a strong sequence conservation signal between bacterial and archaeal rProteins related by circular permutation. This conserved sequence is structurally colocalized with conserved rRNA, indicated by TwinCons scores of rRNA alignments of bacterial and archaeal groups. This combined analysis revealed deep co-evolution of rRNA and rProtein buried within the deepest branching points in the tree of life.
Highlights
Advances in sequencing and metagenomics [1] allow biologists to observe alterations in cancer genomes [2], identify genetic novelty [3], characterize microbial communities [4], fold protein sequences [5], and unravel ancestral relationships [6,7,8]
Can we look back far beyond the Last Universal Common Ancestor (LUCA) [10] and establish whether segments of ribosomal proteins share ancestry with segments of ribonucleic acids (RNA) polymerase (RNAP) or translation factors, and determine how these segments interplay with nearly RNA? For that purpose, here we establish and apply a score of conservation within a composite alignment, which is a multiple sequence alignment containing two pre-defined sequence groups
ConSurf can detect conservation within proteins and RNA across an entire alignment column, while Zebra2 detects signature residues in a composite alignment
Summary
Advances in sequencing and metagenomics [1] allow biologists to observe alterations in cancer genomes [2], identify genetic novelty [3], characterize microbial communities [4], fold protein sequences [5], and unravel ancestral relationships [6,7,8]. Here we establish and apply a score of conservation within a composite alignment, which is a multiple sequence alignment containing two pre-defined sequence groups. In a composite alignment of a single gene, one group could be bacterial sequences while the other could be archaeal sequences. A composite alignment might contain paralogous sequences, where two different but related genes form the groups. One group could be an initiation factor and the other group could be an elongation factor. In this scenario, the homology within each group is known or suspected, but homology between the groups is in question. The method developed here, called TwinCons, can be applied to either protein or nucleic acid sequences. Classical methods consider only conserved and nonconserved alignment positions, while TwinCons differentiates between universal, signature, and non-conserved segments or positions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
