Professor Mark Pallen's Inaugural Lecture at Warwick Medical School, University of Warwick, April 15th 2014. Storified version of lecture: https://storify.com/mjpallen/palleninaugural

1. Nothing in
Microbiology makes
Sense except in
the Light of Evolution
Professor Mark Pallen

2. Online extras
 Live tweet
#palleninaugural
 Slides available at
http://www.slideshare.net/mpallen/pallen-
inaugural-warwickfinal
 Online guide
 https://blogs.warwick.ac.uk/microbialun
derground
 https://storify.com/mjpallen/palleninaug
ural
 YouTube
 https://www.youtube.com/user/Warwick
MedicalSchool
 https://www.youtube.com/user/pallenm
Unofficial after-
lecture drinks at
The Varsity pub,
CV4 7AJ

3. In Memoriam
Fred Sanger
13 Aug 1918 – 19 Nov 2013
Carl Woese
Jul 15, 1928 – Dec 30,
2012
Steve Jobs
Feb 24, 1955 – Oct 5,
2011
Si monumentum requiris, circumspice

4. Acknowledgements
―We were united by a common love of Science,
which we thought sufficient to bring together
persons of all distinctions, Christians, Jews,
Muslims and Heathens, Monarchists and
Republicans.‖
Joseph Priestley on the Birmingham Lunar
Society, 1793

5. Acknowledgements
―We were united by a common love of Science,
which we thought sufficient to bring together
persons of all distinctions, Christians, Jews,
Muslims and Heathens, Monarchists and
Republicans.‖
Joseph Priestley on the Birmingham Lunar
Society, 1793

6. I am not obsessed with Darwin…
 ...despite quoting him at my
wedding, calling my first two
children Emma and Charles,
being on first name terms with
two of his descendants, writing
scholarly works about his views
on religion!
 John van Wyhe, Alison Pearn,
Randal Keynes are all
obsessed with Darwin…
 …I just have a passing interest
 But I don‘t want to let my
audience down…

7. What is to be covered…
 History of life
 History of science
 History of me and my
science
 Century by century,
 Decade by
decade…

8. The Origin: November 24th 1859
1859-1959 1960s 1970s 1980s 1990s 2000s 2010s

9. From 1859 to 1959
Darwin's Influence on Modern Thought
 notion of branching evolution
 common descent of all living
things from a single origin
 the mechanism of evolution is
(largely) natural selection
 evolution gradual
 no major discontinuities
 evolutionary biology, by contrast
with physics and chemistry, is a
historical science
 evolutionist attempts to explain
events/processes that have
already taken place
 feeds on variation and
randomness
 banishing typology and
determinism
Ernst Mayr
Jul 5, 1904 – Feb 3, 2005

10. Tools to think with…
Darwin’s Notebooks
If we choose to let conjecture run wild,
then
animals our fellow brethren in pain,
disease,
death and suffering, and famine, our
slaves in the most laborious works, our
companions in our amusements; they may
partake from our origin in one common
ancestor; we may be all netted together

11. From 1859 to 1959: Genetics
 1860s
 Mendel‘s experiments on peas
 1900s onwards
 Rediscovery of Mendel (de Vries,
Correns, Bateson)
 Soma/germ-line distinction
(Weismann)
 Chromosomes; mutations (Morgan)
 1940s
 ―Modern Synthesis‖ of Evolution and
Genetics (Fisher, Haldane, Wright,
Dodzhansky, Mayr)

12. From 1830s to 1959: Computing
 1837
 Analytical Engine: Babbage
 1842
 Ada Lovelace: first program
 1854
 Boolean algebra
 1936
 Turing machines
 1950s
 First transisterized computers

13. From 1859 to 1959: Germ Theory
 1860s
 Pasteur demolishes
spontaneous generation
 1870s
 Koch links anthrax to bacteria
 Cohn founds bacterial
taxonomy
 Cohn and Darwin correspond
 1880s
 TB; cholera; diphtheria;
antiserum

14. From 1859 to 1959
1942: Bacteria don’t have genetics…
―[bacteria] have no genes in the
sense of accurately quantized
portions of hereditary
substance; and therefore they
have no need for the accurate
division of the genetic system
which is accomplished by
mitosis‖
Julian Huxley, 1942

15. From 1859 to 1959
1951: Bacteria do have genetics
Chapter on‗Mutation and selection in
microorganisms‘ in Dobzhansky‘s 1951
Genetics and the Origin of Species
―Demerec (1945) and Luria (1946)
showed that penicillin-resistant strains of
Staphylococcus aureus arise by mutations
which survive in the presence of enough
penicillin in the medium to kill most
individuals of the parental strain.‖

16. From 1859 to 1959
1953: from Darwin to DNA
Darwin, Nature April 1882
“through the kindness of Mr W.
D. Crick of Northampton…”
Crick and Watson,
Nature, April 1953
beetle
bivalve

17. 1960: I am born!

18. 1964: Dobzhansky’s dictum

19. Sidestep: Sequences
Genes: DNA
Proteins
Information Storage
Genes consist of sequences of
characters from
4-base alphabet ACTG
Information into Action
Proteins consist of sequences of
characters from
20-amino-acid alphabet
encode
All the genes, all the DNA in a bacterium
=
its Genome Sequence
its complete “genetic blueprint”

20. 1965: Zuckerkandl and Pauling
sequence homology and molecular phylogenetics

21. Sidestep: Sequence homology
 Languages and
informational
macromolecules consist
of sequences of
characters that show
―descent with
modification‖
 Similarity due to descent
from common ancestor
(homology) can be used
to infer function or
meaning
 one, two, three
 eins, zwei, drei
 un, deux, troi
Hittite (20-13th C BCE)
nu NINDA-n
ezzateni watar-ma
ekutteni
Now you will eat
BREAD,
And you will drink water
Hrozný, Bedřich (1917)
nu BREAD-n
ezzateni watar-ma
ekutteni

22. 1970s: Sanger invents DNA sequencing

23. 1970s: me
 Wallington High School
 ―Must learn to control his
grasshopper mind!‖
 ―The primary purpose of a
liberal education is to make
one's mind a pleasant place
in which to spend one's time”
Sydney J. Harris
 DNA is not in the textbooks!
 But Cambridge entrance
exam asks for protein
sequence assembly!

24. 1980s: me
 Fitzwilliam College,
Cambridge
 ―How much genome is there in
a pork pie?‖
 Final year project on Leprosy
 London Hospital
 Royal Free
 Barts
“I know that I ought to feel ashamed of days and evenings thus spent, but
as some of my friends were very pleasant and we were all in the highest
spirits, I cannot help looking back to these times with much pleasure.”
“During the three years which I spent at
Cambridge my time was wasted, as far as
the academical studies were concerned…”

25. 1987: Bacteria join Darwin’s tree of life
Eucarya Archaea
Bacteria

26. As the 1980s turned into the 1990s
 Exploiting computers to
find sequence homology
 Helicobacter pylori
 A bacterial urease shows
homology to a plant
urease!
 Clostridium difficile
 Butanol fermentation
genes
 (same pathway that earned
Chaim Weizmann the
Balfour Declaration)
 Reverse transcriptase and
a group II intron

27. From 1990s: Proteins and domains
The search for distant homologies
Signal Peptide A
B
Coiled coil domain C
D
Transitivity of Homology
Proteins consist
of domains
Distant Homology
Signal Peptide
―Let two forms have not a single character in common, yet if these extreme
forms are connected together by a chain of intermediate groups, we may at
once infer their community of descent, and we put them all into the same
class.‖
Origin of Species CHAPTER 14

28. From 1990s: Stress!
 The lab-cultured bacterium is an
artifact
 ―Life...in a state of nature is solitary,
poor, nasty, brutish and short‖ Thomas
Hobbes
 In the wild, bacteria face stressful feast
fast or famine lifestyle
 During infection, host responses cause
stress
 WT-funded PhD on starvation stress
in Salmonella
 BBSRC grant to use microarrays in
follow-up study

29. From 1990s: Stress!
Emma
Nov 5th 1995
Charlie
Mar10th 1997
Natasha
Aug 3rd 1999
Tom
Jan 7th 2002
Final
Late October 1995

30. From 1990s: Bacterial Pathogenomics
Discovered Biology
Undiscovered Biology

31. From 1990s: Bacterial Pathogenomics

32. From 1990s: Tools to think with…
Internet Databases

33. 1999-2001
From Barts to Belfast to Birmingham

34. 2000s
E. coli: avoiding typological thinking
And God created E.
coli K-12 MG1655…?

35. 2000s: Evolution in E. coli
Genome Degeneration and convergent evolution

36. 2000s: Evolution in E. coli
Virulence Effectors

37. 2000s: Evolution in E. coli and beyond
The Evolution of Complexity

38. 2000s: Darwin Days
Evolution as obsession…
…and reward

39. 2008: Genomes as documents
of evolutionary history

40. Sequencing
singularity
From 2008: High-throughput sequencing
brings genomes for the masses

41. 2010s: Bacterial evolution within outbreaks

42. 2011-2012 Acinetobacter Outbreak
 First reported case July 2011 (military patient)
 Outbreak lasted 80 weeks and involved 60
patients, including military and civilian patients
 >90 isolates from patients and environment
genome-sequenced on Illumina MiSeq, including
multiples from same patient (different time and
body sites)
 Reconstructed phylogenetic tree and potential
transmission chains, focussing infection control
efforts on an operating theatre

43. 2010s: Darwin in the drug store
 Genomes of two Acinetobacter baumannii isolates from
single patient sequenced
 before tigecycline therapy (susceptible) and after therapy
(resistant)
 Eighteen changes detected between AB210 and AB211
 nine non-synonymous, including mutation in adeS which accounts
for resistance
 Three sections of early genome missing in late genome,
 loss of DNA repair gene, causing increase in mutation rate?
 Planned work on MDR TB
 Madikay Senghore, Martin Antonio

44. 2011: Social Evolution
Open-Source Genomics

45. 2013 onwards: genome to metagenome
Challenging Gram and Koch

46. 2013 onwards: ancient DNA
Genomes as documents of human history

47. 2013 onwards: Negativicutes
when Gram stain and genealogy conflict

48. 2014 onwards : Tools to think with
CLIMB consortium

49. 2014 onwards: Tools to think with…
Enterobase
 "More individuals are born than can
possibly survive. A grain in the
balance will determine which
individual shall live and which shall
die—which variety or species shall
increase in number, and which shall
decrease, or finally become extinct...‖
 ―The slightest advantage in one being,
at any age or during any season, over
those with which it comes into
competition, or better adaptation in
however slight a degree to the
surrounding physical conditions, will
turn the balance.‖
 Origin of Species, 1859, Charles
Darwin
 "More proposals are submitted than can
possibly be funded. A grain in the
balance will determine which proposal
shall be funded and which shall die—
which research group or institution shall
increase in number, and which shall
decrease, or finally become extinct…‖
 ―The slightest advantage in one proposal,
at any stage or during any meeting, over
those with which it comes into
competition, or better adaptation in
however slight a degree to the
surrounding political conditions, will turn
the balance.‖
 Origin of Research Projects, 2014

50. There is grandeur in this view of
life, with its several powers having
been originally breathed into a few
forms or into one; and that whilst
this planet has been cycling on
according to the fixed law of
gravity, from so simple a
beginning endless forms most
beautiful and most wonderful
have been, and are being, evolved.
Back to 1859: Darwin’s grandeur