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Metablome and Evolution
“Nothing in biology makes sense except in the light of Evolution”
(Theodosius Dobzhansky)
Basic Modes of Genetic Transfer
Horisontal / Lateral
Transfer of genetic
material from one
genome to another
Vertical
Transfer of a genetic
material to the next
generation
Basic Modes of Molecular Evolution
•Gene duplication
•Gene losses
•Mutations
•HGT
Gene Duplication
Prevalence of gene duplications
•Gene duplications occurs in all 3
kingdoms of life
•Often referred as paralogous
Zhang, 2003
Gene Duplication
•3 mechanisms:
1. Unequal crossing over
2. Retroposition
3. Chromosomal (or
genome) duplication
•Different fates:
1. Pseudo-genization
2. Conservation of gene
function
3. Sub-functionalization
4. Neo-functionalization
Zhang, 2003
Gene Loss
Sometimes less is more
•Frequent in all 3 kingdoms of life
•Gene loss can provide an opportunity for adaptation
•Gene loss can be a cause of species-specific phenotype
•An example: pseudo-genization of MYH16 (a sacromeric myosin
gene) at the time of emergence of the genus homo is thought to
be responsible for size reduction of masticatory muscles, which
may allowed the expansion of our brain.
Horizontal (Lateral) Gene Transfer
•Transfer of a gene from one genome to another.
•An outcome, not a specific genetic mechanism.
•Inter-domain or intra-domain transfer
DNA Transfer Between Bacterial Cells
Mechanisms:
•Transformation
•Conjugation
•Transduction
DNA Transfer Between Bacterial Cells
A complicated mechanism
HGT in Eukaryotes
•Probably less frequent than in prokaryotes
Endosymbiont-origin
•2 types of gene transfer in eukaryotes:
Species
•Most of the gene transfers are in the prokaryoteeukaryote direction
•High variation in the frequency of HGT in different eukaryotes
Detecting HGT
•Unexpected ranking of sequence similarity among homologs (BLAST)
•Unexpected phylogenetic tree topology
•Unusual phyletic patterns (phyletic pattern = the pattern of species
present or missing in the given cluster of orthologs)
•Conservation of gene order between distant taxa (HGT of operons)
•Anomalous nucleotide composition (such as codon usage or GC
content). Applicable only to recent HGT events.
HGT Vs. Gene Duplication
•Problem: any putative HGT event
can be explained by a series of
gene losses and duplications
•An example: evolution of the
anaerobic glycerol-3-phosphate
dehydrogenase
1. Scenario 1: a single
HGT event from
bacteria to archea
2. Scenario 2: 10 gene
losses after the last
common ancestor
•However, there could be a
problem in the phylogenetic
tree…
So… how does the biosphere look like?
Adaptive evolution of bacterial metabolic
networks by horizontal gene transfer
Pal, C., Papp, B. and Lercher, M.J
Nature Genetics 37, 1372-1375
E.Coli K-12
•931 unique biochemical
reactions and 904 genes
HGT Vs. Gene Duplication
Is there any difference between eukaryotes and prokaryotes?
•E.Coli – 107 proteins
•S.cerevisiae – 285 proteins
HGT Vs. Gene Duplication:
E.coli K-12
•Lawrence et al. 1991
In the last 100 million years:
1 – gene duplication (out of 451)
•Construction of a
phylogenetic tree (51
proteobacteria species)
15-32 – HGT
•Identification of the most
parsimonious scenarios for
HGT and gene losses
HGT is more frequent in E.coli K-12 in the recent period
Why is HGT More Frequent?
•The most difficult thing in gene duplication is retaining the
duplicated gene until they develop distinct functions
•The initial preservation of the two copies depends on the
effect of enhance gene dosage
•There are number of mechanisms that facilitate gene transfer
What are the Selective Pressures Driving the
Acquisition of Foreign Genes?
Flux balance analysis of the metabolic network
•Only 7% of the HGT genes are
essential under nutrient-rich conditions.
•The genes that were frequently
gained or lost were environmentspecific.
The Topological Effect of HGT on the Network
Supplementary table 2:
•The number of independent HGT events was highly variable across different
enzymatic pathways
•Genes in central pathways of the network had undergone few transfer events
HGT – At Which Stage of the Metabolic
Network?
√
Transport
First reaction
Intermediate
Biomass Production
Gene Loss and Gain: 1 at a
Time or As a Set of Genes?
•Physiologically coupled genes were identified (flux coupling analysis)
•Two cases:
- fully coupled enzyme pairs
- directionally coupled enzyme pairs
•Both fully and directional coupled enzymes were much more often
gained or lost together than would be expected by chance
Physiological modules tend to be conserved during evolution
•30% of the fully coupled pairs are encoded in the same operon
•75% of the fully coupled pairs that were gained together are
encoded in the same operon
Gains of physiologically fully coupled pairs together most
likely occurred in 1 step
Conclusions:
In E.coli K-12:
•In the recent period HGT is more frequent than gene duplication
•HGT is involved in transfer of environment-specific genes
•HGT occurs mainly in the peripheral reactions of the metabolic pathway
•HGT frequently takes place in a set of genes
Pathway Evolution:
1. Pathways might have evolved
spontaneously without adopting
existing enzymes
2. “Retro-evolution” of pathways:
selective pressure on a pathway
targets the successful production
of its end-product
3. Evolution from multifunctional
enzymes
4. Whole pathways (as a unit)
become duplicated
5. “Recruiting” enzymes from existing
pathways (a mosaic, or a
“patchwork” )
Schmidt et al, 2003
Pathway Evolution:
•Another factor for pathway evolution: metabolites
•Several possibilities:
-Early stages of metabolic evolution occurred by enzymedriven evolution, whereas more recent pathways are
metabolite-driven
-Constraints by structural and chemical properties of highly
represented metabolites might have already biased the
evolutionary space explored in the early days of pathway
evolution
Pathway Evolution:
•There are several highly abundant metabolites (H2O or ATP)
•Pathways evolve and concentrate around these central metabolites
•They lead to short pathway distances in the network
Oxygen
•Earth was created ~4.5 billion years ago
•Between 3.2 and 2.4 billion years ago- the first production of O2 by an
organism
•Within 100 million years O2 built up in Earth’s atmosphere
•O2 caused major changes on Earth:
1. Many of the reductants that were so
abundant were depleted
2. New metabolic pathways were introduced
3. Protective pathways evolved to treat ROS
4. Enabled the Cambrian “baby boom”
Metabolic Network Expansion
•Based on the fact that there is a hierarchical ordering of metabolic
reactions
•The procedure starts with one or more initial compounds = seed
•Reactions take place, which form new compounds.
•The new compounds can be used as substrates in subsequent steps
•The process ends when no new products are generated, and no new
reactions are possible.
Metabolic Network Expansion
•The reactions are taken from a base set of biochemically feasible
reactions (KEGG).
•The reactions are from a collective, not from one organism.
•Currently, there are 6836 reactions in KEGG across 70 genomes and
involving 5057 distinct compounds
•Sampling of 105 highly variable seed conditions.
Metabolic Network Expansion
The Effect of Various Metabolites on the Total
Number of Reactions in Ecosystem Level
Metabolic Networks
The Effect of Various Metabolites on the Total
Number of Reactions in Ecosystem Level
Metabolic Networks
What does it mean?
•There is a convergence into 4 groups
•Each group shares >95% identical reactions and metabolites.
•The networks in smaller groups are nested within those in larger group
•Transitions between smaller groups and between subgroups are
determined by the availability of biomolecules involved in the
assimilation and cycling of key elements
The Effect of Various Metabolites on the Total
Number of Reactions in Ecosystem Level
Metabolic Networks
O2
•Networks simulated in the presence of oxygen are found in a
separate group, unreachable under any anoxic conditions
•Group IV has 105 more reactions than anoxic conditions of group III
•52% of the additional reactions used O2 indirectly
The Effect of Oxygen
• Two representative networks were seeded with / without O2
• The seed included putative prebiotic set of metabolites (NH3, H2S,
CO2, ATP/ADP, NAD+/H, pyridoxal phosphate and tetrahydrofuran)
*Without highly
abundant
metabolites
•http://prelude.bu.edu/O2/networks.html
The Effect of Oxygen
Anoxic Conditions
Oxic Conditions
2162 reactions
1672 metabolites
Consistent with group III
3283 reactions
2317 metabolites
Consistent with group IV
The Effect of Oxygen
The Effect of Oxygen
Obligate aerobes
Facultative aerobes
Strict anaerobes
•Adaptation to O2 occurred after the major prokaryotic divergence
on the tree of life (support of geological and molecular evolutionary
analyses)
The Effect of Oxygen
•Oxic network expansion
was most profilic in
eukaryotes and aerobic
prokaryotes
•Eukaryote-specific
reactions make up ~50%
of the oxic network (Vs.
21% of the anoxic
network)
Oxygen – Conclusions
• Oxygen enabled at least 103 more reactions
• Most of the change was an introduction of new pathways
• Adaptation to O2 occurred after the major prokaryotic divergence
on the tree of life
• Oxygen contributed mostly to eukaryotes
So relax and breathe- it’s good for evolution!
Final Conclusions
•There are two major mechanisms for evolution: Horizontal and
vertical gene transfer
•We saw an extensive research of E.coli K-12 genome evolution
•Metabolites can influence the evolution process
•We saw an example of O2 effect on the evolution process
Thank you!