Sequence Alignment

            An investigator who has an aim of inferring the evolutionary, structural and functional relationships between the sequences from different species, he would analyze the similarities and differences in the nucleotide bases or amino acid sequences. The most common method used for the comparative study is Sequence Alignment which provides the mapping between the residues of two or more sequences. 

In the sequence alignment, Gaps & Insertions, Global Alignment and Local alignment must be considered based on what is the purpose of the research or study. One may consider all of these. 

Gaps and Insertions: These are for studying the mutations in gene sequences. here, an investigator would achieve the better correspondence between two sequences, if he introduces a gap in sequence. similarly, he would allow an insertion in other sequence. Biologically, this corresponds, introducing a new DNA into a gene of interest. 

Global Alignment: For this type of alignment, Needleman-Wunsh algorithm is used... It assumes that two nucleotides are basically similar over the entire length of one another. the alignment attempts to match both sequences from one end to another, even though parts of the alignment are not convincing. 

Local Alignment: For this type of alignment, Smith-Waterman algorithm is used. it searches for the residues of the two sequences which match well and it considers only those parts of the two sequences which have good similarities. 

Figure shows the difference between Global and Local Alignments. 

Fig: Global Alignment vs Local Alignment

Types of Sequence Alignments: 

There are two types of Sequence Alignments

1) Pair wise sequence alignment

2) Multiple sequence alignment

1) Pair Wise Sequence Alignment: 

           This type of alignment can be used to find the similarities between two sequences at a time. But, the similarities are efficient to calculate and used for the methods which do not require precision. Method is best for finding the similarities of two sequences using local or global alignment techniques. There are two methods, dynamic-programming and dot-matrix methods. Commonly used tools are FASTA and BLAST. 

a) Dot Matrix: A visual representation of the match between two sequences. Axis represents one of the two sequences to be compared. When two sequences share similarities over their entire length, a diagonal line will extend from one corner to the diagonally opposite corner in the dot plot. In the dot plot, the diagonal stretches represent if two sequences share patches of the similarities. 

b) Dynamic Programming: This method is not a computer programming. It just involves the fixed set of rules and mathematics to find the solution. This can be applied to produce the local alignments using Smith-waterman algorithm and global alignments via Needleman-Wunsh algorithms. 

2) Multiple Sequence Alignment: 

               This type of alignment involves the finding the similarities between more than two sequences in a given set of query.. It tries to match more than two sequences. That makes it the extension of pair wise alignment. This method is often used for the identification of the conserved regions across a group of sequences which may be evolutionary related. The alignments can be used for constructing the phylogenetic trees to identify the evolutionary relationship between the set of sequences under study. The multiple sequence alignment can be achieved by dynamic programming, progressive method and motif finding. 

                   In progressive method, the alignment between set of sequences are achieved by first aligning the most similar sequences and then aligning the less similar sequences. 

                           In Motif Finding method, the alignment attempts to align the short conserved sequence motifs between the sequences. It is also called as Profile Analysis. 

Commonly used tools for multiple sequence alignments are ClustalW, MAP, T-Coffee and PIMA.