For drawing an evolutionary relationship among several protein sequences, the phylogenetic tree is usually constructed through maximum likelihood-based algorithms. To improve the accuracy of these methodologies, many parameters like bootstrap methods, correlation coefficient and residue-substitution models are presumably over-ranked to derive biologically credible relationships. Although the accuracy of protein sequence alignment and the substitution matrix are preliminary constraints to define the biological accuracy of the overlapped sequences/residues, the alignment is not iteratively optimized through the statistical testing of residue-substitution models. The study majorly highlights the potential pitfalls that significantly affect the accuracy of an evolutionary protocol. It emphasizes the need for a more accurate scrutiny of the entire phylogenetic methodology. The need of iterative optimizations is illustrated to construct a biologically credible and not mathematically optimal tree for a sequence dataset.
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