Question

Which one of the following tools can reliably establish an evolutionary link between two proteins and align them even if they share very low degree of sequence similarity?

1. BLAST

2. PSI-BLAST

3. ClustalW

4. FASTA

Detailed Explanation

When working with protein sequences that share very low sequence similarity, establishing an evolutionary relationship can be challenging. However, specialized bioinformatics tools have been developed to address this issue, helping researchers identify evolutionary links even between distantly related proteins. Let’s look at each option in more detail:

1. BLAST (Basic Local Alignment Search Tool)

BLAST is one of the most widely used sequence alignment tools. It is fast and efficient for comparing protein or nucleotide sequences against databases. However, BLAST primarily works well for detecting similarities between sequences that are relatively similar. It performs local sequence alignments and identifies regions of similarity. When sequences are highly divergent or share very low similarity, BLAST may struggle to identify significant alignments. While it’s a good tool for more closely related sequences, it is not the best for detecting evolutionary links between proteins with very low sequence similarity.

2. PSI-BLAST (Position-Specific Iterative BLAST)

PSI-BLAST is an advanced version of BLAST that improves upon the basic BLAST algorithm. It is specifically designed to identify distant evolutionary relationships between proteins, even when they share very low sequence similarity. PSI-BLAST uses iterative searching, where an initial BLAST search is followed by further searches using a position-specific scoring matrix (PSSM) derived from the results. This allows PSI-BLAST to detect more remote evolutionary links by refining the search with each iteration, making it much better suited for aligning proteins with low sequence similarity.

Correct Answer: 2 (PSI-BLAST)

PSI-BLAST can reliably establish an evolutionary link between two proteins even when they share a very low degree of sequence similarity. It’s particularly effective for detecting evolutionary relationships between distant homologs, making it the ideal choice for such tasks.

3. ClustalW

ClustalW is a widely used tool for multiple sequence alignment. It uses a progressive alignment approach and is ideal for aligning a group of similar sequences to find conserved regions. While ClustalW works well when the sequences share moderate to high similarity, it may not be as effective at aligning highly divergent sequences that share very low sequence similarity. It does not have the iterative nature of PSI-BLAST and therefore may not be able to reliably establish evolutionary links between very distantly related proteins.

4. FASTA

FASTA is another sequence comparison tool, similar to BLAST, that searches for local similarities between protein sequences. While FASTA can perform well for closely related sequences, it doesn’t have the iterative nature or ability to adjust to low-similarity sequences in the way PSI-BLAST does. Like BLAST, it may not perform well for detecting evolutionary links when the sequences are highly divergent.

Conclusion

When working with proteins that share a very low degree of sequence similarity, PSI-BLAST is the most reliable tool for establishing evolutionary links and aligning these proteins. Its iterative nature allows it to refine searches and detect distant homologs, making it the best option for this specific task. Other tools like BLAST, ClustalW, and FASTA are useful for different types of sequence comparison but are not as effective for aligning proteins with low sequence similarity.