1. Review: can we distinguish foreign from native genes? GC-content = [G] + [C] [total nucleotides] SQ2: List the two triplets that code for Lys. What proportion of each is used in Borrelia burgdorferi compared to Mycobacterium tuberculosis? Is this finding surprising? Why or why not? AAU Asn 0.80 AAC Asn 0.20 AAA Lys 0.80 AAG Lys 0.20 AAU Asn 0.21 AAC Asn 0.79 AAA Lys 0.26 AAG Lys 0.74 Mycobacterium tuberculosis Borrelia burgdorferi 29% GC content65% GC content

2. SQ4: The GC content of Bacillus anthracis is 33.97%. By analysis of codon use, would it likely be easier to detect a foreign gene originating from Borrelia burgdorferi or from Mycobacterium tuberculosis? AAU Asn 0.80 AAC Asn 0.20 AAA Lys 0.80 AAG Lys 0.20 AAU Asn 0.21 AAC Asn 0.79 AAA Lys 0.26 AAG Lys 0.74 Mycobacterium tuberculosis Borrelia burgdorferi 29% GC content65% GC content Can we distinguish foreign from native genes?

3. organism 1 TTT TCT GAA TCC GTA GAC GTT organism 2 TTT TCT GAA TCA GCA GAC GTG GUU Val GUC Val GUA Val GUG Val GCU Ala GCC Ala GCA Ala GCG Ala How do genomic differences arise? Point mutation revisted

4. Addition/deletion of DNA Point mutation organism 1 TTT TCT GAA TCC GTA GAC GTT organism 2 TTT TCT GAA TCA GCA GAC GTG GUU Val GUC Val GUA Val GUG Val GCU Ala GCC Ala GCA Ala GCG Ala Silent mutation How do genomic differences arise?

5. Single base mutations TransitionsTransversions Purine for purine or pyrimidine for pyrimidine Purine for pyrimidine or pyrimidine for purine

6. Point mutation organism 1 TTT TCT GAA TCC GTA GAC GTT organism 2 TTT TCT GAA TCA GCA GAC GTG Transition: purine purine pyrimidine pyrimidine Transversion: purine pyrimidine How do genomic differences arise?

7. Tautomerization of bases C T G A C* T* A G

8. DNA replication can “lock in” a mutation Mutations can arise as a consequence of misincorporation during replication

9. How to distinguish foreign from native genes? SQ7: There are two codons each for 9 of the amino acids. Choose any one of these 18 codons. Create a transition mutation in the third position of the codon. What is the result? Create a transversion mutation in the third position. What is the result? In the third position, are transition mutations or transversion mutations more likely to result in a change in the amino acid encoded?

12. How do differences arise between genomes? Addition/deletion of DNA Point mutation Keeping track of gene variants – Concepts of ortholog / paralog

13. Speciation event leading to orthologs Gene duplication gives rise to paralogs Horizontal transfer leads to xenologs Orthologs, Paralogs, and Xenologs

14. Orthologs vs Paralogs SQ5: Are genes B1 and C2 orthologs or paralogs? How to predict orthology with imperfect information?