Query on sequence analysis

Question

[anju57115]

What might be the possible reasons behind getting poor scores after alignment of two homologous sequences?

[Andrzej Zielezinski]

Many homologous sequences (even between closely related species) evolve beyond the point where their homology can be recognized by a simple sequence alignment.

[apa@stowers]

1. How did you align them?
2. Why do you say they are homologous if they have poor alignment scores? (assuming alignment was done properly)
3. Are they supposed to be orthologs? Distant orthologs often have distant sequence similarities. Also, it is not hard to find false positives in some orthology databases.

Answer 1

[mike.thon]

Either the sequences are very divergent (low sequence similarity) or they are not aligned correctly.