Comparison of DNA Sequences with Dynamic Programming and Scoring Scheme

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Questions and Answers

What is the main purpose of using the BLOSUM matrices?

  • To calculate the frequency of mutations in a cluster
  • To align protein sequences with large insertions and deletions
  • To increase the distance between sequences (correct)
  • To identify the ancestral protein sequences

How are the BLOSUM matrices numbered in relation to the PAM matrices?

  • Randomly
  • Inversely (correct)
  • Consecutively
  • Based on percentage identity

What does the BLOSUM50 matrix represent?

  • Clusters with exactly 50% sequence identity
  • Clusters with over 50% sequence identity (correct)
  • Clusters with less than 50% sequence identity
  • Clusters with up to 50% sequence identity

How are probability ratios expressed in the context of substitution matrices?

<p>As log odds (D)</p> Signup and view all the answers

Why are substitution matrices considered symmetrical?

<p>Because the order of sequence alignment does not matter (D)</p> Signup and view all the answers

In the context of substitution matrices, what does symmetrical mean?

<p>The order of alignment does not change the score (D)</p> Signup and view all the answers

How do BLOSUM matrices differ from PAM matrices?

<p>BLOSUM matrices are based on higher percentage sequence identity (D)</p> Signup and view all the answers

Why was the BLOSUM62 matrix created?

<p>To align sequences with at least 62% identity (C)</p> Signup and view all the answers

What is a characteristic of log odd ratios in substitution matrices?

<p>They are calculated without ancestral sequence knowledge (D)</p> Signup and view all the answers

Why are BLOSUM and PAM matrices crucial for sequence alignment?

<p>They provide a robust scoring scheme for alignment algorithms (D)</p> Signup and view all the answers

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Study Notes

Sequence Alignment

  • Global alignment of DNA sequences using dynamic programming and a scoring scheme is possible.
  • Scoring scheme:
    • Match: +3
    • Mismatch: -2
    • Gap: -3

Practice Questions

  • Align DNA sequences using dynamic programming and the provided scoring scheme.
  • Examples:
    • Seq 1: GCTTAGC
    • Seq 2: GCATTGC

Gap Penalty

  • Gap penalty score: g(g) = -d - (g -1) e
  • Linear gap penalty score: d = gap opening penalty, e = gap extension penalty, g = gap length
  • Affine gap penalty score: g(g) = -d - (g -1) e

Scoring Insertions or Deletions

  • Using GAP penalty, score insertions or deletions.
  • Example:
    • Total Score: 4
    • Total Score: 8 + (-3.2) = 4.8

Substitution Matrices

  • Used to score substitution events in alignments.
  • Particularly important in protein sequence alignments.
  • Each scoring matrix represents a particular theory of evolution.
  • Examples of substitution matrices:
    • Identity scoring matrix
    • Genetic code scoring scheme
    • Chemical Similarity Scoring
    • PAM substitution matrices

Identity Scoring Matrix

  • Simplest scoring scheme.
  • Score 1 for identical pairs.
  • Score 0 for non-identical pairs.
  • Unable to detect similarity.

Genetic Code Scoring Scheme

  • Introduced by Fitch in 1966.
  • Scores based on the number of nucleotide base changes required to interconvert the codons for the two amino acids.
  • Used in the construction of phylogenetic trees and in the determination of homology between protein sequences.

Chemical Similarity Scoring

  • Introduced by MacLachlan in 1972.
  • Gives greater weight to the alignment of amino acids with similar physico-chemical properties.
  • Amino acids are classified based on polar or non-polar character, size, shape, and charge.

PAM Substitution Matrices

  • Constructed by Dayhoff, Schwarz, and Orcutt in 1978.
  • Based on 71 protein families with 85% identical sequences.
  • Obtained frequencies for residue X being substituted by residue Y over time period Z.
  • Ignores evolutionary direction.
  • Based on 1572 residue changes.
  • Defined a substitution matrix as 1 PAM (point accepted mutation) if the expected number of substitutions was 1% of the sequence length.

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