Dating bacterial evolution Julian Parkhill Royal Society, London, - - PowerPoint PPT Presentation

Julian Parkhill Royal Society, London, July 2014

Dating bacterial evolution

• Bacteria leave no fossil record, so dating lineages is difficult
• Previous best estimates were based on divergence of

Salmonella and E. coli and gave a rate of 6x10-9 mutations per synonymous site per year

• This has led to hypotheses that many bacterial diseases are
• ld, and the youngest may have been associated with the

Neolithic revolution, or expansion of humans out of Africa

Estimating bacterial mutation rates

Staphylococcus aureus population structure by MLST

CC5 CC8 CC45 CC30 CC22 CC15 CC51 CC25 CC9 CC39 CC1 CC12 TW20 (ST239)

SNPs in 63 closely-related Staphylococcus aureus (ST239) 6,714 total SNPs; 4,310 SNP sites in core sequence

Harris et al (2010) Science 327:469

Random occurrence of SNPs in ST239

mutation rate = 3.3 × 10−6 per site per year = 7.5 SNPs per genome per year

• Bacteria have measurably evolving populations

Harris et al (2010) Science 327:469

Identifying transmission within S. aureus ST329

Harris et al (2010) Science 327:469

Congruence of tree and lack of recombination allows ready identification of intercontinental transmissions 15 SNPs to LCA ~ 1.5 years 81 SNPs to LCA ~ 9 years

Maximum likelihood tree of 200 isolates

Deep divergences between different patient isolates

10_d 10_b 10_a 10_c 25_a 1_c 1_h 1_b 1_f 1_d 1_g 1_e 32_b 32_a 5000 SNPs

Tightly Clustered isolates Loosely Clustered isolates

1 1 _ c 21_d 5_f 5_i 1 1 _ a 21_c 21_b 5 _ c 5 _ m 5_n 5_o 11_e 5 _ j 11_b 16_a 2 3 _ a 5 _ h 4_b 5_d 4_a 5_p 5_g 21_a 5_e 5_k 5 _ a 5_b 5_l 209SNPs 11_d

Mycobacterium abscessus phylogeny

Bryant et al. 2013 Lancet 381:1551

1900 1970 1980 1990 2000 2010 1890

Patients(4(&(5 M.a.$abscessus

11_c 2 1 _ d 5 _ f 5_i 11_a 2 1 _ c 2 1 _ b 5_c 5_m 5_n 5 _

• 11_e

5_j 11_b 16_a 23_a 5_h 4_b 5 _ d 4 _ a 5_p 5_g 2 1 _ a 5 _ e 5_k 5_a 5 _ b 5 _ l 11_d

Estimated(age(of( common(ancstor

Dating of possible M. abscessus transmission events

Bryant et al. 2013 Lancet 381:1551

Vibrio cholerae – El Tor dated tree

Mutreja et al. 2011 Nature 477:462

Vibrio cholerae – repeated global transmission

Wave 3

2005-09 1989-97 2003-07

Wave 2

1992-2002 1993-98 1981-85 1937-61

Wave 1

1975-86 1966-71 1967-89 1969-73 1969-81 1974 1969-73

Mutreja et al. 2011 Nature 477:462

Vibrio cholerae – introduction to Haiti

Katz et al 2013 mBio 4:e00398

Bordetella pertussis phylogeny

First documented pertussis outbreak: Paris 1578 MRCA 1678 (1587-1752) MRCA 286 BC (1582 AD-1330 BC) Harris et al 2013 mBio 5:e01074

250 350 100 200 300 50 150 SCBU MRSA screen positive Community Maternity ward MRSA screen negative SCBU MRSA screen negative P16 P26 P20 P8 P24 P1 P2 P3 P4 P5 P6 P7 P9 P10 P11 P12 P13 P14 P15 P17 P19 P22 P25 P23 P21 ID P18

H

P25 P22 P21 P8 P9 P13 P10 P17 P14 & 23 P7 P20 P26 P6 P1 P4, 16 & 19 P2 & 3 P5 P15 P11 & 12 P24 1 2 3 4 5 6 7 8 9 10 11 SNPs from root

• &

H H H H H H H H H H H Hx2 Hx2 Hx5

SCBU MRSA outbreak

Harris et al. 2013 Lancet Infect Dis. 13:130

• Dating bacterial evolution gives us clinically useful information
• It also informs us about the origin of pathogenic lineages
• The evolution and emergence of many bacterial pathogen lineages is

very recent

• Traditional ideas of pathogen emergence alongside key events in

human evolution (e.g. the Neolithic Revolution) may be untrue

• Pathogen emergence may be a rapid and ongoing process
• This would imply that pathogen extinction is equally frequent

Conclusions

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