Transcript Epidemiology

"Nothing in biology makes sense
except in the light of evolution"
Theodosius Dobzhansky (1900-1975)
Genomes of living organisms sequenced
between 1995 and 2002
eubacteria
eukaryote
Archaea
Molecular search for the Last Universal Common Ancestor (LUCA)
"All the organic beings that have ever lived on this Earth may
be descended from some single primordial form"
Charles Darwin: "Origin of Species"
Life appeared on the Earth 3.5 to 3.8 x 109 years ago, soon after the planet was formed
(Archean sedimentary rocks).
The first phyla that emerge in the tree of life based on rRNA sequences are hyperthermophylic. This led to the hypothesis that the last universal common ancestor (LUCA)
and possibly the original living organism was hyperthermophylic.
What was the nature of such a primordial form? How did the transition from this first form
of life of all extant biological species take place? What was the LUCA gene content?
The computationally- and experimentally-derived (random gene-knockouts) minimal
gene-set might be as low as 250-300 genes. The present estimate suggest that LUCA
genome could have only 500-600 genes.
Late-Archaean biosphere
acc. Nisbet i Sleep (2001)
Hyperthermophile
biofilms and mats
Water
CO2
SO4
Sulphate
reducers
Fermenters
Methanogens
CH4 H2S
Holdfast
H2
LUCA
Hadean
Tree and timescale of life
acc. S. B. Hedges, 2002
Eubacteria
(Bacteria)
Billion years ago
1
Cy
Ap
Pl
An
Ps
Eukaryotes
(Eukarya)
Archaebacteria
(Archaea)
0
Fu
Cy
Mi
Ap
Pl
An,
Fu
1
Am
2
3
Eubacteria
(Bacteria)
Archaebacteria
(Archaea)
Billion years ago
0
Eukaryotes
(Eukarya)
Ps
Am?
Mi
2
Eu?
3
Eu
4
Last common ancestor
Origin of life
An early 1990s view
Last common ancestor
4
Origin of life
1.0 – D. melanogaster
1.15 – C. elegans
1.55 – A. thaliana, S. cerevisiae
2.6 – E. coli,
3.8 – Methanobacterium thermoautotrophicum
The 2002 view
Understanding basic mechanisms of genetic diversity
It is estimated that there are now recognized at least 1.5 million living species of all
organisms on the Earth. There were many more from the beginning of timescale
of life.
The basic mechanisms shaping the evolution of living species are:
exon-shuffling,
polyploidy,
segmental duplication of eukaryotic chromosomes,
horizontal gene transfer (HGT),
symbiotic and mutualistic associations.
Exon shuffling:
An example of ancestral triosephosphate isomerase (2)
acc. W. Gilbert et al. (1986)
Millions of years ago
1500
1000
500
Human (6)
Rabbit
Chicken (6)
Fish
Maize (8)
Progenote
Budding yeast (0)
Aspergillus (5)
E. coli (0)
B. stearothermophilus (0)
C. An evolutionary tree from AA sequence
Exon shuffling: An example of ancestral triosephosphate isomerase (1)
acc. W. Gilbert et al. (1986)
A. Three dimentional structure
of the enzyme with:
coils – α-helices,
arrows – β-sheets
COOH
NH2
13 14
cys asn
38
glu
78
ser
107 108
glu phe
152
glu
183 184
glu val
210
gly
237 238
lys pro
NH2
COOH
glu
38
met
13
ser
78
glu leu
107 108
glu phe
107 108
gln ala
180 181
asp
152
glu glu
132 133
gly
210
trp
169
B. Comparison of proteins sequences of maize, chicken and the fungus Aspergillus
phe
240
Segmentally duplicated regions in the Arabidopsis genome
Individual chromosomes are presented as horizontal grey bars. Coloured bands connect
corresponding duplicated segments. Duplicated segments in reversed orientation are
connected with twisted coloured bands.
Horizontal gene transfer (HGT) and the origin of species:
lessons from bacteria
In bacteria, HGT is widely recognized as the mechanism responsible for the
widespread distribution of antibiotic resistance genes, gene clusters encoding
biodegradative pathways, pathogenicity and symbiosis determinants.
Massive HGT events occurred ~2 billion years ago, when the Earth changed from
reducing to oxidizing atmosphere.
Bacterial and viral DNA are constantly integrating in the chromosomes of plants
and animals today by conjugation, transformation (T-DNA of A. tumefaciens),
retroviruses and integrative viruses.
Why are the genomes of endosymbiotic bacteria so stable?
Bacterial genomes are continuously modified by the gain and loss of genes. HGT is
one of the most important mechanisms of bacterial evolution.
The comparative analysis of endosymbiotic bacterium Buchnera aphidicola (640 kb)
has revealed high genome stability associated with the absence of chromosomal
rearrangements and HGT events during the past 150 million years. The loss of genes
involved in DNA uptake and recombination in the initial stages of endosymbiosis
underlies this stability. By contrast, two strains of E. coli: K-12 and OH 157:H7 with
only 4.5 Myr of divergence, exhibit genomes whose homology is interrupted by
hundreds of DNA segments.
Extensive loss of genes is a general attribute of the evolution of endosymbiotic
bacteria. Genome stability of microsymbionts is responsible for its co-evolution with
the eukaryotic hosts. This is not the case for facultative symbionts whose genomes
are much larger (e.g. rhizobial species symbiotising with legume plants; 4.5 – 7.5 Mb).
Symbiotic interaction between legume and nodule-forming rhizobia
Root
hair cell
Sucrose
Rhizobia
HOST CELL
Infection thread
(invagination of
root hair cell
membrane)
Malate
BACTEROID
N2 Fixation
Nod gene activation
Infected
cell
NH 4
Symbiosome
membrane
Glutamine
Rhizobia enter the root cortex
cell through the infection thread
+
Asparagine
Matabolism of infected cells in a root
nodule. Glutamine and asparagine
are the main products of N2 -fixation
N2
Yellow lupine root nodule morphology
Cross – section of lupine nodule (42 dpi)
nodule
cortex
bacteroid
tissue
meristematic
zone
vascular
bundle
Mature lupine root nodules (42 dpi)
Primate phylogenetic relationship based on molecular and fossil
record analyses
Haplorhini
Simiiformes
Catarrhini
Cercopithecoidea
Lemuriformes
Lorisiformes
Galago
Tarsiiformes
Tarsilus
Platyrrhini
Cebus
Cercopithecinae
Colobinae
Macaca
Hominoidea
Hylobatidae
Hylobates
Symphalangus
Pongidae Hominidae
Pongo
Gorilla Pan
0 Homo
4-6
7-9
14
Mya
18
25
35-45
50-60
65-85
Modern humans (Homo sapiens) and chimpanzees (Pan paniscus and Pan troglodytes) are located in the same genus (Homo) with
a common ancestor living 4-6 Mya. A divergence 7-9 Mya is accepted for separation of gorilla (Gorilla) and Homo clade. An estimate
of 14 Mya for the divergence of orangutan (Pongo) and African Apes. Gibbon lineage divergence took place about 18 Mya. The Old
World monkeys (Cercopithecoidea) include many primate species with baboons (Papio), mandrills (Mandrillus) and Cercopitheques
(Cercopithecus) mainly found in Africa as well as macaques (Macaca) predominant in Asia. Divergence for Hominoidea and Cercopithecoidea was estimed to 25 Mya.
Birth of "human-specific" genes important
for primate evolution
Humans and the Great African Apes share very similar chromosome structure and
genomic sequence at the DNA level with 98.5-99% homology (chimpanzee).
What makes us different at the genetic level from the closest relatives - Antropoids?
A recent major breakthrough was identification of "human-specific" genes. Also,
specific chromosomal regions have been mapped that display all the features of
"gene nurseries" and could have played a major role in gene innovation and
speciation during primate evolution.
Two highly conserved human genes were identified (PRM2, histon-like protein
essential to spermatogenesis and FOXP2-transcription factor involved in speech
and language development) which were probably the selection targets in recent
human evolution.