metablome and evolution “ nothing in biology makes sense except in the light of evolution ”...
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Metablome and Evolution
“Nothing in biology makes sense except in the light of
Evolution”
(Theodosius Dobzhansky)
Horisontal / Lateral Vertical
Transfer of genetic material from one genome to another
Transfer of a genetic material to the next generation
Basic Modes of Genetic Transfer
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 LossSometimes 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
HGT in Eukaryotes
•Probably less frequent than in prokaryotes
•2 types of gene transfer in eukaryotes:
Endosymbiont-origin
Species•Most of the gene transfers are in the prokaryoteeukaryote 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…
Adaptive evolution of bacterial metabolic networks by horizontal gene transferPal, 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 DuplicationIs there any difference between eukaryotes and prokaryotes?
•E.Coli – 107 proteins
•S.cerevisiae – 285 proteins
In the last 100 million years:
1 – gene duplication (out of 451)
15-32 – HGT
HGT Vs. Gene Duplication:E.coli K-12
HGT is more frequent in E.coli K-12 in the recent period
•Lawrence et al. 1991
•Construction of a phylogenetic tree (51 proteobacteria species)
•Identification of the most parsimonious scenarios for HGT and gene losses
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 environment-specific.
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 the recent period HGT is more frequent than gene duplication
In E.coli K-12:
•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 enzyme-driven 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
•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
Pathway Evolution:
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.
•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
•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
What does it mean?
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
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 metabolitesConsistent with group
III
3283 reactions2317 metabolites
Consistent with group IV
The Effect of Oxygen
Strict anaerobesObligate aerobes Facultative aerobes
•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