1 Molecular evidence of HIV transmission in a criminal case Metzker, Michael L. et al. (2002) Proc. Natl. Acad. Sci. USA 99,

2 Guilty Sequence - scientists map a murder weapon “ In 1998, a Louisiana doctor was convicted of attempting to murder his ex-girlfriend, a nurse. The murder weapon was a syringe of HIV-infected blood drawn from a patient under the doctor's care. ”

3 Criminal investigation  Circumstantial evidence that the doctor injected blood from a patient of his into this ex-girlfriend.  How can this be proved using a bioinformatic approach?

4 Phylogenetic analysis  Which HIV sequences are most similar to the victim ’ s sequences?  Show common ancestry  Show directionality of the transfer

5 A little on HIV  Extreme heterogeneity: 1.Error-prone nature of the reverse transcriptase 2.Rapid viral turnover 3.High viral burden

6 A little on HIV  Within each patient there are many different viral strains (intrahost divergence)

7 History of the virus: gp120 PATIENT VICTIM CONTROLS ©2002 National Academy of Sciences, U.S.A.

8 History of the virus: RT  The patient: AZT resistant and AZT sensitive sequences of RT  The victim: AZT resistant sequences

9 History of the virus: RT The patients’ sequences are paraphyletic: the victims’ sequences are nested within them. VICTIM PATIENT

10 Summary  This case created a precedent for the use of phylogenetic analysis in court of law “It is ironic that this case originated in Louisiana, which enacted the Balanced treatment for Creation-Science and Evolution-Science Act in 1982”