Introduction to Evolution (Biological!) and Evolvability General - - PowerPoint PPT Presentation

Introduction to Evolution (Biological!) and Evolvability

General Principles of Evolution Adaptive vs Non-adaptive selection Conservation, Constraints and Convergence Examples Mutation/Selection/Evolution in Bacterial Systems Mutation/Repair Horizontal Transfer Induced Mutagenesis Eukaryotic Evolution in Real time Darwin’s Finches HSP90- Development and Evolution DNA Shuffling / In Vitro Evolution

Evolution: a process in which the gene pool of a population

gradually changes in response to environmental pressures, natural selection, and genetic mutations.

Evolvabilty: the capacity of an organism to evolve

Evolution is generally thought as the progression from simple to complex but this is not necessarily true. e.g. Host- parasite interactions / symbiotic relationships

Niche: the ecological ‘environment occuppied by a species

Speciation: the process giving arise to new species, usally

through splitting of lineages (geographic/ temporal isolation, reproductive isolation). The ‘key element of evolution’.

Adaptive evolution: Selection for a modification of a species

that makes it more fit for reproduction and/or existence under the conditions of its environment. Natural Selection

e.g Darwin’s finches

Non-adaptive evolution: Selection for a modification of a

species that is selected but is not immediately tied to fitness.

e.g. Cichlid fishes of Lake Victoria

Darwin’s Finches * woodpecker finch *

evolve tool use in order to take advantage of the niche usually occupied by woodpeckers.

A group of finches that are found on the Galapogas Islands that have evolved from a single species of finch that colonized the islands approximately 0.5-1 million years ago. That have evolved into 14 present day species that occupy a vaiety of niches on the

• islands. They are not the best example of adaptive

radiation but they are of historical interest because Darwin was the first to descibe their behavior in detail and collect samples. Also from the work of Peter and Rosemary Grant over the past few decades have described the evolution of a vertebrate species within this group

Cichlid Fish of Lake Victoria

• over 200 species have evolved in the past 750,000 years
• many by adaptive evloution based on food sources

(e.g. fish, zooplankton, mollucs,algae, fish scales)

• some clusters have evolved based on mate selection, differing
• nly in the color of the male fish (non-adaptive)

Morphological diversification in metazoans is not reflected in the underlying cellular/molecular mechanism for generating diversification. Morphological diversity arises from cellular diversity but the underlying language and devices are the same. i.e - there is conservation at the molecular level.

• signal transduction (sensing / repsonding to the environment including other cells
• cytoskeletal scaffolds that can generate diversity at the cell level
• haploid genomes (single copy of genes) limits mutational space that can sample
• Cambrian “explosion” -

The Cambrian Explosion / The Burgess Shale

An explosion in the diversity in metazoan body plans exemplified by the bizarre world of the Burgess Shale (Yoho National Park).

Roman arch Mayan arch

• St. Louis arch

from Gerhart and Kirscher 1997

The evolution of the Roman arch requires many elements of the door to be individually modified- specialization. The evolution of the Mayan arch requires

• nly the rearrangement of the existing parts -

temporal and spatial modifications. The St. Louis arch is constructed from entirely new technologies.

Evolution at the cellular levels ustilizes all three types of mechanisms however the “Mayan arch” strategy is used predominantly. Conserved building blocks used to build novel structures- modularity in design There are constraints imposed by using conserved blocks - i.e. they are embedded in other processes (gene duplication)

Morphological convergence - similar structure have evolved

• independently. This can be only at the functional level or at both a

functional and morphological level.

from Gerhart and Kirscher 1997

GeneralProblems when thinking about evolution:

• defining niche (ecological)
• defining fitness / fitness landscapes
• defining species

reproductive vs geographic isolation bacteria

• time scales make experimentation difficult/impossible with vertebrates

Evolution is a balance between stability and variability.

Mutation, Selection and Evolution in Bacterial Systems

The balance between variability and stability

Mutagenesis at the sequence level

Spontaneous error rate of replication Mutagens (environmental, metabolic byproducts) Inducible ‘mutations’

• mutational hotspots
• error prone replication

DNA rearrangements Recombination (minimal in most bacteria because of single copy chromosome)

Phase Variation: reversible changes in expression patterns that are due to

‘reversible’ geneotypic changes

Switching frequencies can differ in each direction

DNA Acquisition:

• conjugation
• plasmids
• transposons (jumping genes)
• integrating bacteriophage
• ‘other’ mechanisms

In contrast to sequence mutations, DNA acquisition mechanisms involve intact genes and functional units.

e.g. antibiotic resistance, toxin production , pesticide degradation

Mutation Rates – set the rate of variability

For E. coli 5 x 10-10 mutations per bp per replication 0.0025 mutations per genome per replication In 1 ml of culture 109 cells 2.5 x106 mutations 500 mutations per gene These rates of spontaneous mutation differ between organisms (even between bacteria)- this is a ‘selected’ phenotype.

Mutation Rates – set the rate of variability

The basal rate of mutation in the absence of environmental mutagens is set by the fidelity of replication, rate of chemical mutation of DNA and the ability or efficiency of DNA repair systems in the bacteria. Many bacteria can alter their mutation rates – I.e. they have some genetic control of their ‘Evolvability’. Bacteria can control the fidelity of replication and the ability or efficiency of DNA repair systems* in the bacteria – in stressful conditions, the mutagenesis rate increases: they accelerate their own evolution.

* - decrease in repair efficiency also facilitates ‘horizontal gene transfer’

Eukaryotic Evolution in Real time Darwin’s Finches

• within approximately 10 years of extreme drought, a

population of finches evolved that was morphologically distinct from the ‘founding population’

• small populations/bottlenecks
• what does this say about the plasticity/evlovability of

Darwin’s finches?

• can this be generalized?

(The Beak of the Finch : A Story of Evolution in Our Time. Jonathan Weiner (1995)) HSP90- Development and Evolution in Drosophila

Hsp90 as a capacitor for morphological evolution

Suzanne L. Rutherford*† and Susan Lindquist* Nature 396, 336 - 342 (1998) ‘heat shock proteins’ - assist in protein folding and degradtion of denatured proteins in the cell (coping with stresses) Hsp90 - an unusual ‘heat shock protein’ that seems to be dedicated to signal transduction proteins that are involved in the cell cycle and development

Observation: In strains with mutant Hsp90 alleles morphological abnormalities arise with high frequency (1-2% of the progeny). This can be mimicked by adding Hsp90 inhibitors to the food supply.

The spontaneous appearance of these developmental abnormalities result from abnormal Hsp90 function. Why? 1) Mutants may be more sensitive to environment and subtle variability in microenvironments of the developing embryos maylead to the observed phenotypes. 2) Hsp90 may be involved in DNA repair and these Hsp90 alleles may have higher mutation rates 3) ‘cryptic’ genetic variability might be expressed to a greater extent i.e. Hsp90 may normal act to suppress genetic variation in several developmental pathways.

‘Folded’ active protein

instability

Refolding by Hsp90

Unfolded Inactive Protein

Normal Conditions

The cell-cell and developmental signal transduction proteins are naturally unstable and the role of Hsp90 is to keep them in their active conformation.

‘Folded’ active protein

instability

Refolding by Hsp90

Unfolded Inactive Protein

Refolding by Hsp90

Stress Conditions

Denaturation Under stress conditions, Hsp90 is recruited in the folding of other proteins and can not maintain sufficient quantities of its normal substrates and development is compromised

Silent polymorphisms exist in the population that become ‘expressed’ under conditions of stress . Natural populations of fruit flies have a ‘reserve’ of diversity that can be explored under conditions of stress. Under conditions of stress, Hsp90 becomes overwhelmed with stress- damaged proteins and consequently there is insufficient ‘Hsp90 activity’ to maintain its normal substrates in a functional mode. (Threshold)

similar situation in Neiserria?

• Robustness. Stability of a phenotypic property to changes in parameters giving

rise to that phenotype.

• Evolvability. The ability to evolve new functions.
• 1. Robustness seems to be a feature of many biochemical/genetic networks

They are stable with respect to perturbations (genetic, environmental)

• 2. Robustness and evolvability appear to be contradictory.

stability is the opposite of evolution

• 3. How can one select for “Evolvability”?

i.e. selecting for a phenotype that will appear in the future.

Robustness and Evolvability

The example of chemotaxis:

Tumble frequency Steady-State Tumble Frequency Adaptation Time Adaptation precision

Adaptation precision (i.e. exact adaptation) is Robust Adaptation time is very sensitive to parameters

Adaptation Time Tumble Frequency “normal’ parameters

Robustness in chemotaxis

Adaptation Time Tumble Frequency

Robustness in chemotaxis

“normal’ parameters Parameter space where precise adaptation works Parameter space where precise adaptation fails (non-chemotactic)

Adaptation Time Tumble Frequency

Robustness in chemotaxis

“normal’ parameters Parameter space where precise adaptation works Parameter space where precise adaptation fails (non-chemotactic) Robustness facilitates evolution within the network- i.e. lets the network explore behavioral space

DNA Shuffling: a single gene or multiple genes are cleaved into fragments

and recombined creating a population of novel gene sequences. The novel genes created by DNA Shuffling are then selected for one or more desired

• characteristics. This selection process yields a population of genes which

becomes the starting point for the next cycle of recombination.

In Vitro Evolution In Silico Evolution

DNA Shuffling Genetic Algorthims

Generate mutants or natural variants Fragment randomly into smaller peices Reassemble

repeat

selection

Note that assembly is ordered.

Some applications of DNA shuffling

Target enzyme Target Change Approach Function effected Kanamycin thermostability >200X mutator strain resistance subtilisin E activity in organic ~ 170-fold error-prone PCR solvents b-lactamase enzyme activity >32,000X DNA shuffling b-galactosidase enzyme activity >1000X specificity DNA shuffling > 66X activity arsenate pathway arsenic resistance 12X increase DNA shuffling (detoxification)

References: Cells, Embryos and Evolution. J. Gerhart and M. Kirschner. Backwell Science Press. (1997) What Evolution Is? Ernst Mayr Basic Books (2001)

Ecology and Evolution of darwin’s Finches. P.R. Grant. Princeton University Press (1986). The Beak of the Finch : A Story of Evolution in Our Time. Jonathan Weiner (1995)