Section A â Edit distance (8 points total)
1. Find the edit distance between ACGAAGTTC and ACCAAGGTGTTC. How do you know it is at most that much? How do you know it is at least that much?
Section B â More on sequence alignment (52 points total)
2. (6 points) Which of the following would be the two most appropriate to assess whether there are regions of homology between two distantly related proteins? Select two.
A) Needleman-Wunsch Algorithm
B) edit distance
C) local sequence alignment
D) global sequence alignment
E) dot plot
3. Consider the following alignment: ACACCAGGTCCCC ACA-----TGACC
a) (3 points) With a match score of +3, and mismatch score of -1, and using a gap penalty of -2, what is the score of the above alignment?
b) (3 points) If we keep the same match score and mismatch score, but use a gap open penalty of -6 and a gap length penalty of -1 per additional residue, what is the score of the previous alignment?
c) (8 points) Using the scoring system used in part b (match +3; mismatch -1; gap open -6 ; gap extension -1), Which of the following alignments is best? Which is worst? How do you know?
A) ACACCAGGTCCC A---CATGA-CC
B) ACACCAGGTCCC ACA---TGACC
C) ACACCAGGTCCC ACATGA----CC
D) ACACCAGGTC-CC ACA-----TGACC
E) ACACCAGGTCCC ACA--TG-ACC
F) ACA---CCAGGTCCC ACATGACC-------
4. Look up the INS gene in Entrez Gene.
a) (2 points) What tag do you put inside square brackets after INS to search for INS as a gene symbol?
b) (2 points) Find the record for the human INS gene. Which chromosome is INS on?
c) (2 points) What is the accession number for the RefSeq record for the shortest mRNA for human INS?
d) (2 points) What is the accession number for the RefSeq record for the human geneâs genomic DNA?
d) (6 points) Using the Needleman-Wunsch program, how could you find the mRNA sequence within the genomic DNA version? Give the best strategy, including the scoring parameters.
e) (4 points) Find the next gene upstream of the INS transcription start site. Which neurotransmitter does the product of this next gene make? How many base pairs separate the two genes?
f) (2 points) Now look up ins-1 as a gene symbol in Entrez Gene. Choose the entry for the worm C. elegans. Which chromosome is it on?
g) (2 points) What is the URL for the Wormbase link on this Entrez Gene record? What is the gene accession number for ins-1 in the C. elegans genome database?
g) (10 points) Perform Needleman-Wunsch alignments between C. elegans INS- 1 protein and Homo sapiens INS preproprotein, using the default parameters, except changing the substitution matrix to PAM10 for one alignment, and PAM50 for the second alignment. Use the following online tool: https://www.ebi.ac.uk/Tools/psa/emboss_needle/ What are the number of identical residues, score, and number of gapped residues for each of the two alignments? What conclusions can you draw about which of the two matrices, PAM10 or PAM50, is more appropriate in this situation?
