unity and diversity in microbial genomes dr. kishore … · 2015-12-25 · budding and appendaged...
Post on 21-Apr-2020
4 Views
Preview:
TRANSCRIPT
UNITY and DIVERSITY in
MICROBIAL GENOMES
Dr. Kishore Sakharkar
The screen versions of these slides have full details of copyright and acknowledgements 1
1
UNITY and DIVERSITY
in MICROBIAL GENOMES
Kishore Sakharkar
National University of Singapore
ksakharkar@gmail.com
2
Microbes everywhere
Amazing but true
More bacteria in our bodies
than human cells!
More different types
of bacterial genes
in our body
than there are human genes!
3
Different shapes of bacteriaCopy right © The M c Graw-Hi l l Com panies , Inc . Perm is s ion requi red for reproduc tion or d is p lay .
Coccus Rod, or bacillus Curved forms: Spirillum/Spirochete
Vibrios (curved rods)Coccobacilli
Mycobacteria Spirilla
Spirochetes
Streptococci
(cocci in chains)
Filamentous
Spirochete
Sta lkHy pha
Coc c us RodSpi ri l lum
Budding and
appendaged
bacteria
UNITY and DIVERSITY in
MICROBIAL GENOMES
Dr. Kishore Sakharkar
The screen versions of these slides have full details of copyright and acknowledgements 2
4
Different sizes
• Size affects rate of nutrient and waste transport across the cell membrane
• Small size � more efficient exchange, support of higher metabolic rate
5
There are now ~200
complete genomes!
Where are we?
Diversity is Good
Parasites vs. free-living organisms
Large genomes vs. small genomes
Archaea vs. Bacteria vs. Eukaryotes
Eucarya
Bacteria
Archaea
6
BacteriaEukaryotesArchea
Genomes sequenced
0
50
100
150
200
250
300
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
Ar chea
Bacter ia
Eukar yo te
UNITY and DIVERSITY in
MICROBIAL GENOMES
Dr. Kishore Sakharkar
The screen versions of these slides have full details of copyright and acknowledgements 3
7
Microbial evolutionary genomics
• Broad questions that are now being addressed:
� How do genomes acquire their contents,
as lineages evolve over long time scales?
� What are the forces that enable complex biological
processes to be maintained?
� How do genes (and their associated functions)
originate in genomes and how are they lost?
� How do biological capabilities move from one organism
to another and how do they persist over space and time?
For each question, answers are likely to depend on the particular niche
and may differ among microbial communities associated with different processes or sites
8
Bacterial lifestyles
• Commensalism
• Mutualism
• Parasitism
9
Topics
• Diversity in genome size
• Unity and diversity in gene order
• Unity and diversity in protein length profi les
• Genome reduction in obligatory intracellular parasites
• Overlapping genes in obligatory intracellular parasites
(common patterns in genome architecture)
UNITY and DIVERSITY in
MICROBIAL GENOMES
Dr. Kishore Sakharkar
The screen versions of these slides have full details of copyright and acknowledgements 4
10
Compared 115 bacterial genomes
Size varies between bacterial genomes
Smaller genomes have lesser number of genes (ORFs)
Konstantinidis et al., 2004, PNAS
Genome size and number of genes
Genome size
R = 0.98
Tot
al num
ber
of ORFs
in the ge
nome
11
• Minimum number of genes to maintain free-living organism
• Mycoplasma genitalium contains only 468 identified
protein-coding genes – Is it the minimal gene set?
• M. genitalium vs. H. influenzae
• Two ancient bacterial lineages, i.e. , Gram-positive
and Gram-negative bacteria, respectively
• 240 genes are orthologous
• Some genes in intermediate steps in essential pathways
are missing? - Nonorthologous gene displacement
• 256 genes are close to the minimal gene set
Minimal genome
Mushegian AR, Koonin EV. (1996) A minimal gene set for cellular life derived by comparison
of complete bacterial genomes. Proc Natl Acad Sci U S A. , 93, 10268-10273
12
Gene order comparison
Sakharkar KR, Chow VT (2004). Exploring genome architecture through GOV
a WWW-based gene order visualizer, Bioinformatics , 20, 984-985
UNITY and DIVERSITY in
MICROBIAL GENOMES
Dr. Kishore Sakharkar
The screen versions of these slides have full details of copyright and acknowledgements 5
13
Gene order as a common theme
in microbial genomes
• Parallel analysis of multiple genomes can contribute
to understanding of their functional subsystems
e.g., operons
• Gene order:
�Genome architecture
�Functions and interactions of the proteins
�Genome and organism evolution
�Genome annotation
14
Conservation of gene order in bacterial
species of the same genus
1
101
201
301
401
501
601
1 101 201 301 401
M. genitaliumvs.
M. pneumoniae
15
Mycoplasma species and gene orderGene order in genomes
Functional description
Multiple genomes
UNITY and DIVERSITY in
MICROBIAL GENOMES
Dr. Kishore Sakharkar
The screen versions of these slides have full details of copyright and acknowledgements 6
16
Conservation of gene order in closely related
reduced bacterial genera
C. trachomatisvs.
C. pneumoniae
1
101
201
301
401
501
601
701
801
901
1001
1 101 201 301 401 501 601 701 801
17
Lack of gene order conservation - even in “closely related” bacteria of the same Proteobacterial subdivision
P. aeruginosavs.
E. coli
18
Protein length profile
Sakharkar KR, Chow VTK (2004). PPD - Proteome Profile Database, In Silico Biol, 4, 0019
UNITY and DIVERSITY in
MICROBIAL GENOMES
Dr. Kishore Sakharkar
The screen versions of these slides have full details of copyright and acknowledgements 7
19
PPD – Proteome Profile Database
Sakharkar KR, Chow VT (2004) PPD - Proteome Profile Database, In Silico Biol, 4, 0019
E.Coli K12Chlamydia trachornatis
Chlamydophila pneumoniae CWL029
Ricketts ia prowazekiiRicketts ia conorii
Comparative length distribution profile: Protein length X (steps) vs. % distribution
Gene product between 700 and 800 amino acids
20
Chlamydophila pneumoniae - causes pharyngitis , bronchitis
and pneumonit is
Chlamydia trachomatis - causes pharyngitis, bronchitis
and pneumonit is
Rickettsia conorii - causes Rocky Mountain spotted fever
Rickettsia prowazekii - causes louse-borne typhus
and Mediterranean spotted fever
Mycobacterium leprae - causative agent of human leprosy
Obligatory genomes and associated diseases
21
Obligatory intracellular parasites possess
small genomes and display a tendency
towards further genome reduction
# of genes decrease with decrease
reduction in genome size
• Reduction targets are potentially
dispensable genes
• Reduction, while adapting
to selective pressure of the niche
Sakharkar KR, Dhar PK and Chow VT (2004). Genome reduction in prokaryotic obligatory intracellular parasites
of humans: a comparative analysis. Int J Syst Evol Microbiol, 54, 1937-1941
0
1000
2000
3000
4000
5000
6000
No. of genes
Genome size (kb)
UNITY and DIVERSITY in
MICROBIAL GENOMES
Dr. Kishore Sakharkar
The screen versions of these slides have full details of copyright and acknowledgements 8
22
Genome compaction by differential
gene loss in obligatory intracellular parasites
Sakharkar KR, Dhar PK and Chow VT (2004). Genome reduction in prokaryotic obligatory
intracellular parasites of humans: a comparative analysis. Int J Syst Evol Microbiol, 54, 1937-1941
Critical questions:
• The size
• The processes
• The content of deletions
23
Their problems
• How to get in host cell
• Inside, how to avoid being killed
• How to multiply
• How to get out � infect new cells
24
0
5
10
15
20
25
30
35
1 00 2 00 3 00 4 00 500 600 70 0 80 0 90 0 1 000 1 10 0 1 20 0 1 30 0 1 40 0 150 0 >1 50 0
R. prowazeki i
R. cono ri i
C. tra chomatis
C. pneumoniae
M. leprae
E. coli
Protein length
distribution
% genome/length
% change
Max. reduction230-600 AA
Metabolic enzymes
Housekeeping genesNot lost
RNA polymerase,Gyrase, adhesion -10
-5
0
5
10
15
20
100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 1400 1500 >1500
R. prowazekiiR. conoriiC. trachomat isC. pneumon iaeM. lep raeE.coli
UNITY and DIVERSITY in
MICROBIAL GENOMES
Dr. Kishore Sakharkar
The screen versions of these slides have full details of copyright and acknowledgements 9
25
0
100
200
300
400
500
600
700
800
50
10
0
15
0
20
0
25
0
30
0
35
0
40
0
45
0
50
0
55
0
60
0
65
0
70
0
75
0
80
0
85
0
90
0
95
0
10
00
>1
000
Protein length (AA )
# o
f pr
ote
ins
E. coliC. trachomatisC. pneunoniaeR. prowazekiiM. lepraeR. conorii
“Backbone genome” and gene loss
M. leprae – genome in reduction
26
More genomes and “backbone genome”
Sakharkar KR. , Sakharkar MK., Chow VT (2005). Footprints of genome reduction in obligatory
intracellular parasites (under review)
Genomes in reductionM. Lepraeand C.burnetti
27
UNITY and DIVERSITY in
MICROBIAL GENOMES
Dr. Kishore Sakharkar
The screen versions of these slides have full details of copyright and acknowledgements 10
28
COG category distribution
0
5
10
15
20
25
30
35
40
J A K L B D Y V T M N Z W U O C G E F H I P Q R S
COG category
% g
en
om
e
R.prowaze kii R.co nor ii
C.trac homatis C.pn eumon iae
M.le pra e E.Coli
Translation
IncreaseJ – TranslationH,I,U - Transports / Metabolism
Life StyleQ – Sec metabolites
& biosynthesis
N - MotilityV - Defense
DecreaseT – TransductionG – Carbo. metabolism
P – InOrg transport
UnknownB - Chromatin structure and dynamics Y - Nuclear structure Z - Cytoskeleton
W - Extracellular structures
29
Common themes/unity
• Genome of size <2Mb
� Intracellular (depend on host)
• Increased, pseudogenes
(more number of genes in decay)
• Increased, transport proteins
(uptake from the host)
30
Overlapping genes
Sakharkar KR, Chandra Verma, and Vincent TK Chow (2004). Comparative study of overlapping genes
in bacteria, with special reference to Rickettsia prowazekii and Rickettsia conorii.Int J Syst Evol Microbiol, 55, 1205-1209
UNITY and DIVERSITY in
MICROBIAL GENOMES
Dr. Kishore Sakharkar
The screen versions of these slides have full details of copyright and acknowledgements 11
31
Overlapping genes
• Overlapping genes have been proposed as a means
of achieving genome reduction by compressing
the maximum amount of information in limited
sequence space
• Detai led analyses of two reduced genomes
with obligatory lifestyle revealed that
mutations at the ends of coding regions
and elimination of intergenic DNA are the main
forces that determine overlapping of genes
32
Directions of overlap
Unidirectional (++)
Unidirectional (--)
Convergent (+-)
Divergent (-+)
>90%
Operons or clusters of gene transcribed together
5’ 3’
Divergent < ConvergentIn divergent 5’ overlap
33
Proportion of genomes represented
by overlapping genes in nine genomes
0
5
10
15
20
25
30
35
40
Chlamydia
trachomatis
Chlamydia
pneumoniae
Mycobacterium
leprae
Rickettsia
prowazekii
Rickettsia conorii
Mycoplasma
genitalium
Mycoplasma
pneumoniae
Clostridium
perfringens
Buchnera
aphidicola
% G
en
om
e
Obligatory ReducedFreeliving
All genes (incl. unknown and hypothetical
Genuine genes
Endosymbiont
UNITY and DIVERSITY in
MICROBIAL GENOMES
Dr. Kishore Sakharkar
The screen versions of these slides have full details of copyright and acknowledgements 12
34
Which genes overlap
• Essential genes
• Genes in operons
35
Conclusion
Common themes
• Genome size
• Protein length profiles
• Niche dependent gene loss
• Backbone genome
• Overlapping genes
36
Thank you!
top related