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CENTER FOR BIOLOGICAL SEQUENCE ANALYSIS Introduction to the Theory of Evolution: Common Descent

CENTER FOR BIOLOGICAL SEQUENCE ANALYSIS Introduction to the Theory of Evolution: Common Descent

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Introduction to the Theory of Evolution:Common Descent

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Classification: Linnaeus

Carl LinnaeusCarl Linnaeus1707-17781707-1778

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Classification: Linnaeus

• Hierarchical systemHierarchical system

– KingdomKingdom

– PhylumPhylum

– ClassClass

– OrderOrder

– FamilyFamily

– GenusGenus

– SpeciesSpecies

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Classification depicted as a tree

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Classification depicted as a tree

SpeciesSpecies GenusGenus FamilyFamily OrderOrder ClassClass

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Theory of evolution

Charles DarwinCharles Darwin1809-18821809-1882

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Phylogenetic basis of systematics

• LinnaeusLinnaeus: : Ordering principle is God.Ordering principle is God.

• DarwinDarwin: : Ordering principle is shared descent from Ordering principle is shared descent from common ancestors.common ancestors.

• Today, systematics is explicitly based on Today, systematics is explicitly based on phylogeny.phylogeny.

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Natural Selection: Darwin’s four postulates

• More young are produced each generation than can survive to reproduce.More young are produced each generation than can survive to reproduce.

• Individuals in a population vary in their characteristics.Individuals in a population vary in their characteristics.

• Some differences among individuals are based on genetic differences.Some differences among individuals are based on genetic differences.

• Individuals with favorable characteristics have higher rates of survival and Individuals with favorable characteristics have higher rates of survival and reproduction.reproduction.

• Evolution by means of natural selectionEvolution by means of natural selection• Presence of ”design-like” features in organisms:Presence of ”design-like” features in organisms:• Quite often features are there “for a reason”Quite often features are there “for a reason”

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Molecular Basis for Heredity: DNA

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Molecular Basis for Heredity: DNA

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Molecular Basis for Variation: DNA Mutation

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Other causes of evolution

• Sexual selection • Genetic drift (bottlenecks, founder effect, neutral evolution)

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Introduction to the Theory of Evolution:The Evidence for Evolution

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The Evil Tree of Evolution

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Evolution Seen as Ungodly

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“Teach the Controversy”

…to help revitalize science education

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Science and Religion are not Contradictory

• Science cannot prove or disprove the existence of GodScience cannot prove or disprove the existence of God

• Evolutionary theory does not deny the existence of God, only a Evolutionary theory does not deny the existence of God, only a literal literal interpretation of the first chapter of Genesis as an exact historical interpretation of the first chapter of Genesis as an exact historical account.account.

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Expected Gaps in Fossil Record

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Fossil Record, Distribution of Living and Extinct Animals

• Older geological strata contain extinct organismsOlder geological strata contain extinct organisms

• Fossils in adjacent strata are typically more similar than fossils in non-adjacent Fossils in adjacent strata are typically more similar than fossils in non-adjacent stratastrata

• Fossils in the top (most recent) strata are very similar to contemporary species Fossils in the top (most recent) strata are very similar to contemporary species

• Fossils become progressively more different from contemporary species in Fossils become progressively more different from contemporary species in progressively older (lower) strata.progressively older (lower) strata.

• Fossils appear in the order which we would predict from the universal tree Fossils appear in the order which we would predict from the universal tree

• Fossils in a specific location are typically more closely related to local Fossils in a specific location are typically more closely related to local contemporary organisms.contemporary organisms.

• Closely related contemporary species are typically also close geographically, Closely related contemporary species are typically also close geographically, regardless of their habitat or specific adaptations. regardless of their habitat or specific adaptations.

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Fundamental Unity of Life

• All species use same genetic material (DNA/RNA)All species use same genetic material (DNA/RNA)

• All species use catalysts (enzymes) based on protein molecules built from the All species use catalysts (enzymes) based on protein molecules built from the same set of 20 amino acids (from more than 390 naturally occurring)same set of 20 amino acids (from more than 390 naturally occurring)

• All species use extremely similar metabolic pathways and enzymes for their All species use extremely similar metabolic pathways and enzymes for their basic metabolism (e.g., glycolysis, the citric acid cycle, and oxidative basic metabolism (e.g., glycolysis, the citric acid cycle, and oxidative phosphorylation).phosphorylation).

• All species use the same genetic code (or minor variations) All species use the same genetic code (or minor variations)

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Fossilized Animals Should Conform to the Universal Tree

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Fossilized Animals Should Conform to the Universal Tree

We have found a quite complete set of dinosaur-to-bird transitional fossils with no morphological "gaps",

Represented by Eoraptor, Herrerasaurus, Ceratosaurus, Allosaurus, Compsognathus, Sinosauropteryx, Protarchaeopteryx, Caudipteryx, Velociraptor, Sinovenator, Beipiaosaurus, Sinornithosaurus, Microraptor, Archaeopteryx, Rahonavis, Confuciusornis, Sinornis, Patagopteryx, Hesperornis, Apsaravis, Ichthyornis, and Columba, among many others

All have the expected possible morphologies.

For instance: Archaeopteryx

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Fossilized Animals Should Conform to the Universal Tree

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Fossilized Animals Should Conform to the Universal Tree

We also have an exquisitely complete series of fossils for the reptile-mammal intermediates, ranging from the pelycosauria, therapsida, cynodonta, up to primitive mammalia.

Interesting example: gradual evolution of anvil and hammer in mammalian middle ear from reptilian jawbones

In the reptilian fetus, two developing bones from the head eventually form two bones in the reptilian lower jaw, the quadrate and the articular.

The corresponding developing bones in the mammalian fetus eventually form the anvil and hammer (incus and malleus) of the mammalian middle ear.

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Fossilized Animals Should Conform to the Universal Tree

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Fossilized Animals Should Conform to the Universal Tree

“Finally, and most glaringly obvious, if random evolution is true there must have been a large number of transitional forms between the mesonychid and the ancient whale: Where are they? It seems like quite a coincidence that of all the intermediate species that must have existed between the mesonychid and whale, only species that are very similar to the end species have been found.”

(Behe 1994)

But: In recent years, we have found several transitional forms of whales with legs, both capable and incapable of terrestrial locomotion.

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Vestigial Structures

• Vestige: a reduced and rudimentary Vestige: a reduced and rudimentary structure compared to the same structure compared to the same complex structure in other organisms. complex structure in other organisms. Vestigial characters, if functional, Vestigial characters, if functional, perform relatively simple, minor, or perform relatively simple, minor, or inessential functions using structures inessential functions using structures that were clearly designed for other that were clearly designed for other complex purposescomplex purposes

• From common descent and the From common descent and the constraint of gradualism, we predict constraint of gradualism, we predict that many organisms should retain that many organisms should retain vestigial structures as structural vestigial structures as structural remnants of lost functions. Note that remnants of lost functions. Note that the exact evolutionary mechanism the exact evolutionary mechanism which created a vestigial structure is which created a vestigial structure is irrelevant as long as the mechanism is irrelevant as long as the mechanism is a gradual one.a gradual one.

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Molecular Evidence

• Phylogenies based on DNA or protein sequences agree remarkably well with Phylogenies based on DNA or protein sequences agree remarkably well with phylogenies based on morphologyphylogenies based on morphology

• This is true regardless of whether functional or non-functional sequences are This is true regardless of whether functional or non-functional sequences are usedused

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For instance: endogenous retroviruses (molecular remnants of a past parasitic viral infection)

The arrows designate the relative insertion times of the viral DNA into the host genome.

All branches after the insertion point (to the right) carry that retroviral DNA - a reflection of the fact that once a retrovirus has inserted into the germ-line DNA of a given organism, it will be inherited by all descendants of that organism

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Gene 1

Enzyme 1

Gene 2

Enzyme 2

Gene 3

Enzyme 3

DB C Vitamin CA

GULOgene

Gulo Enz

Vitamin C

Not so in primates…

Portion of Working GULO Gene in Rat:

Matching GULO Pseudogenes in 4 Primates Note Deletion

In most mammals

Molecular Evidence: Pseudogenes and Vitamin C

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Etc., etc., etc.

• Ontogeny: often an organism’s evolutionary history is represented temporarily in its Ontogeny: often an organism’s evolutionary history is represented temporarily in its development (hind limbs in whales and snake embryos, tails in human embryos, gill development (hind limbs in whales and snake embryos, tails in human embryos, gill pouches in mammal embryos, ...)pouches in mammal embryos, ...)

• Atavism: Occasionally contemporary animals are born with characters representative of Atavism: Occasionally contemporary animals are born with characters representative of remote ancestors (living whales with hindlimbs, human babies born with tails, ...).remote ancestors (living whales with hindlimbs, human babies born with tails, ...).

• Atavisms and vestiges are always found to be consistent with the universal tree (organisms Atavisms and vestiges are always found to be consistent with the universal tree (organisms always have atavistic or vestigial characters that are predicted to have been present in an always have atavistic or vestigial characters that are predicted to have been present in an ancestor).ancestor).

• Extensive genetic change has repeatedly been observed in lab and wild populations of Extensive genetic change has repeatedly been observed in lab and wild populations of animalsanimals

• Numerous observations of morphological change in populations of living organisms Numerous observations of morphological change in populations of living organisms (changes in color, size, length, width, and number of physical aspects of organisms)(changes in color, size, length, width, and number of physical aspects of organisms)

• Many observations of newly acquired functions (bacteria that evolved to use nylon and Many observations of newly acquired functions (bacteria that evolved to use nylon and pentachlorophenol as their sole carbon source, bacteria that evolved to synthesize new pentachlorophenol as their sole carbon source, bacteria that evolved to synthesize new amino acids, crustaceans that evolve new defenses to predators, etc.)amino acids, crustaceans that evolve new defenses to predators, etc.)

• Experimental observations of speciation (according to the biological species concept): Experimental observations of speciation (according to the biological species concept): plants (with and without polyploidization), fruit fly, house fly, apple maggot fly, gall former plants (with and without polyploidization), fruit fly, house fly, apple maggot fly, gall former fly, flour beetles, polychaete worm. (Major changes seen for asexual species also)fly, flour beetles, polychaete worm. (Major changes seen for asexual species also)

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The Role of Evolutionary Theory in Contemporary Biomedical Research

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Theory of evolution as the basis of biological understanding

”Nothing in biology makes sense, except in the light of evolution.

Without that light it becomes a pile of sundry facts - some of them interesting or curious but making no meaningful picture as a whole” T. Dobzhansky

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Use of Animal Model Organisms

• Model organism: a species that is studied to understand biological phenomena, with the Model organism: a species that is studied to understand biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. workings of other organisms.

• This is only possible because fundamental biological principles such as metabolic, This is only possible because fundamental biological principles such as metabolic, regulatory, and developmental pathways, and the genes that code for them, are conserved regulatory, and developmental pathways, and the genes that code for them, are conserved through evolutionthrough evolution

• For instance: pre-clinical testing in animals (rodents often used, but species closer to For instance: pre-clinical testing in animals (rodents often used, but species closer to humans in the universal tree are preferred when it is important to test under more human-humans in the universal tree are preferred when it is important to test under more human-like conditions)like conditions)

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• Very fundamental systems can be Very fundamental systems can be examined in very distant species (e.g., examined in very distant species (e.g., cell cycle regulation examined in cell cycle regulation examined in yeast)yeast)

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Interpretation of Multiple Alignments

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Interpretation of Multiple Alignments

Conserved features assumed to be important for functionality

For instance: conserved pairs of cysteines indicate possible disulphide bridge

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• Darwin: all organisms are related through descent with modification

• Prediction: similar molecules have similar functions in different organisms

Protein synthesis carried out by very similar RNA-containing molecular complexes (ribosomes) that are present in all known organisms

Sequences are related

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Sequences are related, II

Related oxygen-binding proteins in humans

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Predicting Function from Sequence

• Prediction of protein function and structure (database searches).

Protein 1: binds oxygen

Sequence similarity

Protein 2: binds oxygen ?

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Database searching

Find similar sequences in database,

Predict function

Database

Query sequence

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BLAST database search on the web

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BLAST database search on the web

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Sequence and Function are not Necessarily Linked

• Proteins can retain function despite extensive changes (e.g., yeast and human cytochrome c are 40% different, but yeast can live with human cytochrome c if its own gene has been deleted)

• On average only 34% of random amino acid changes in a protein will disrupt function (Guo et al., 2004, Protein tolerance to random amino acid change. PNAS 101(25):9205-10)

• Cytochrome c from various bacterial species have virtually no sequence similarity but fold up into the same 3D structure and perform the same function

• Different structure, same function. For instance: carbonic anhydrase in mammals, plants, and methane-producing bacteria have no structural or sequence similarity but perform same function.

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Drug Resistance in Bacteria and Viruses

Several types of antibiotics inhibit protein synthesis by binding to ribosomes

Antibiotic resistance often involves point mutations in the ribosome that disrupt binding of the antibiotic

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Drug Resistance in Bacteria and Viruses

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Influenza Subtypes

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Reconstruction of 1918 Flu strain

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Influenza Pandemics and Bird Flu

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Sequence of 1918 Flu Provides Information About Important Adaptations for Human to Human Transfer

• Sequence analysis has identified 10 amino acids that are found in Sequence analysis has identified 10 amino acids that are found in polymerase genes of human influenza viruses (including 1918 strain) polymerase genes of human influenza viruses (including 1918 strain) but not in avian virusesbut not in avian viruses

• These could be important for adaptation to the human hostThese could be important for adaptation to the human host

• Several human isolates of 1997 Hong Kong H5N1 virus and 2004 Several human isolates of 1997 Hong Kong H5N1 virus and 2004 Vietnam H5N1 virus have one of these changesVietnam H5N1 virus have one of these changes

• Other changes in other genes probably also necessaryOther changes in other genes probably also necessary

• Would be interesting to find historical isolates of viruses predating 1918 Would be interesting to find historical isolates of viruses predating 1918 to fully reconstruct and understand the adaptation processto fully reconstruct and understand the adaptation process

• Would be interesting to use mutational and epidemiological modeling to Would be interesting to use mutational and epidemiological modeling to predict chance of virus adapting.predict chance of virus adapting.