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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? Borrelia burgdorferi AAU Asn 0.80 AAC Asn 0.20 AAA Lys 0.80 AAG Lys 0.20 29% GC content Mycobacterium tuberculosis AAU Asn 0.21 AAC Asn 0.79 AAA Lys 0.26 AAG Lys 0.74 65% GC content Can we distinguish foreign from native genes? 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? Borrelia burgdorferi AAU Asn 0.80 AAC Asn 0.20 AAA Lys 0.80 AAG Lys 0.20 29% GC content Mycobacterium tuberculosis AAU Asn 0.21 AAC Asn 0.79 AAA Lys 0.26 AAG Lys 0.74 65% GC content How do genomic differences arise? Point mutation revisted organism 1 TTT TCT GAA TCC GTA GAC GTT organism 2 TTT TCT GAA TCA GCA GAC GTG GUU GUC GUA GUG Val Val Val Val GCU GCC GCA GCG Ala Ala Ala Ala How do genomic differences arise? Addition/deletion of DNA Point mutation organism 1 TTT TCT GAA TCC GTA GAC GTT organism 2 TTT TCT GAA TCA GCA GAC GTG Silent mutation GUU GUC GUA GUG Val Val Val Val GCU GCC GCA GCG Ala Ala Ala Ala Single base mutations Transitions Purine for purine or pyrimidine for pyrimidine Transversions Purine for pyrimidine or pyrimidine for purine How do genomic differences arise? Point mutation organism 1 TTT TCT GAA TCC GTA GAC GTT organism 2 TTT TCT GAA TCA GCA GAC GTG Transition: Transversion: purine pyrimidine purine pyrimidine purine pyrimidine Tautomerization of bases C T G A C* T* A G DNA replication can “lock in” a mutation Mutations can arise as a consequence of misincorporation during replication 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? How do differences arise between genomes? Addition/deletion of DNA Point mutation Keeping track of gene variants – Concepts of ortholog / paralog Orthologs, Paralogs, and Xenologs Speciation event leading to orthologs Horizontal transfer leads to xenologs Gene duplication gives rise to paralogs Orthologs vs Paralogs SQ5: Are genes B1 and C2 orthologs or paralogs? How to predict orthology with imperfect information? A1 AB1 Species A B1 B2 C1 C2 Species B C3 Species C