Question 4 of 6 Intermediate Concept
What is the difference between sequence identity and sequence similarity?
Short answer
Identity counts exact residue matches at aligned positions. Similarity can also credit conservative amino acid substitutions using an explicitly defined scoring scheme.
Why
Compute identity as identical aligned positions divided by a declared denominator, such as aligned columns or the length of a reference region. For proteins, similarity usually incorporates chemically tolerated substitutions from a matrix like BLOSUM, but software definitions of positives and percentages can vary. A leucine-to-isoleucine replacement can be similar under a matrix without being identical.
Always report alignment coverage, gap treatment and scoring method alongside percentages. A 95% identical 20-residue stretch is not interchangeable with 45% identity across an entire enzyme. For DNA, a simple exact-match identity is often more meaningful than an unspecified similarity percentage.
Neither metric independently establishes orthology, functional equivalence or evolutionary direction.
Common mistakes
- Comparing percentages from different tools without matching coverage, denominators and substitution criteria
The interviewer might ask next
Can two proteins show high similarity but relatively low identity, and why?