Structurally and Evolutionarily Consistent Alignment of Closely-related Proteins and their coding DNA sequences, simultaneously.
Multiple sequence alignment (MSA) is widely used for evolutionary analysis and structures modeling of proteins. Traditionally, proteins and their coding DNA sequences (CDSs) are aligned and analyzed separately. However, drastically different alignments/phylogenetic trees/evolutionary relationships/conclusions can be drawn on the same set of data.
Here we present a new alignment strategy and a software tool, codon and amino-acid unified sequence alignment (CAUSA), which aligns protein sequences and their CDSs simultaneously, in a unified manner. For each coding sequence, each codon is taken as a whole, divisible unit, CAUSA allows internal gap placement, and thus, increases the accuracy of alignments, because of the integration of two different kinds of information that are stored separately in DNA and protein.
Using the envelope protein (gp120) of the human immune deficiency virus (HIV) as a model example, it is demonstrated that CAUSA is evolutionarily and structurally more accurate and more consistent than traditional DNA, protein or codon level alignments. CAUSA not only gives highly precise alignment suitable for evolutionary analysis of closely-related proteins, but also explains how base/AA substitutions, insertions and deletions edit coding DNA sequences and drive protein structure evolution, through some unexplored codons changes, including codon fusion, codon splitting, substitution-induced deletion, and indel-induced partial frameshifting.
CAUSA is more convenient than DNA, protein, and codon alignment methods because it does three different alignments at once!
Moreover, it is free!
Welcome to download the CAUSA software, latest version 2.1.18!
We are still working on this software to make it better and provide more data to prove its advantages.
If you want to report a bug or have any questions, please do not hesitate to contact me by email to:
Xiaolong Wang: Xiaolong@ouc.edu.cn
Related publications:
[1]. Wang Xiaolong, Yang Chao. (2015) CAUSA 2.0: accurate and consistent evolutionary analysis of proteins using codon and amino acid unified sequence alignments. PeerJ PrePrints 3:e1486 https://dx.doi.org/10.7287/peerj.preprints.1214v1
[2]. Wang Xiaolong, Fu Yu , Zhao Yue , Wang Qi , Pedamallu Chandra Sekhar , Xu,Shuang-yong , Niu Yingbo , and Hu Jingjie. (2011) Accurate Reconstruction of Molecular Phylogenies for Proteins Using Codon and Amino Acid Unified Sequence Alignments (CAUSA). Available from Nature Precedings http://precedings.nature.com/documents/6730/version/1