Genes and Evolution Molecular clocks and phylogenies

1. Genes and Evolution Molecular clocks and phylogenies Systematics A definition of taxonomy Phylogenies Characters and traits Homology and homoplasty Simple Phylogenies Molecular evolution Substitutions Synonymous and nonsynonymous Selection and neutral theory Molecular phylogenies Molecular clocks Adam Price

2. Defining Systematics and Taxonomy Systematics- the study of the diversity of organisms Taxonomy- the science of classification of organisms taxis = Greek to arrange, classify Why? Explains evolutionary relationships Intrinsically interested Underpins an understanding of biology- e.g. ecology, conservation Important in applications to human life

3. Monkey Gorilla Chimpanzee Human Ferns Conifers Peas Rice Phylogeny- the history of descent of a group of organisms from a common ancestor from Greek- phylon = tribe, race genesis = source Conventionally represented by a phylogeneic tree

4. Phylogenic trees Phylogentic trees are based on comparison of traits individuals with common traits are placed together Character = a feature of the organisms (e.g. flower colour, height) Trait = one form of a character (blue flower colour, short height) Traits inherited from a common ancestor are termed homologous Traits that differs from the ancestor are termed derived Phylogenies are trees that best explain the distribution of homologous and derived traits in the organisms studied (the focal group).

5. Scoring traits to make a simple phylogeny

6. Lungs Claws or nails Feathers Four-chambered heart Fur, mammary glands Relative evolutionary time A simple phylogeny Hagfish Perch Salamander Lizard Crocodile Pigeon Mouse Chimpanzee Jaws Ancient events Recent events

7. Paraphyletic Polyphyletic Monophyletic Phylogenetic trees Outgroup Monophyletic taxa include all descendants of a common ancestor Paraphyletic taxa include some, but not all, descendants of a common ancestor Polyphyletic taxa includes members with more than one recent common ancestor Outgroup a lineage closely related to the focal group

8. The problem of homoplastic traits traits that appear similar but are not related through ancestry Convergent evolution- independent evolution of similar traits due to similar selection pressure (e.g. wings in birds and bats) Parallel evolution- independent evolution of common traits in organisms sharing distant relatives (e.g. patterns of butterfly wings). Evolutionary reversals- the loss of a derived trait (e.g. limbs of snakes, teeth of frogs).

9. Traits used in phylogenetics Morphology and developmental the importance of fossils Molecular Protein sequences Genetic markers DNA sequences

10. The advantages of molecular traits 1/ They directly reflect the underlying process of evolution- changes in the hereditary material 2/ There are a vast number of potential traits 3/ They can detect difference between very closely related organism (even those that show no phenotypic difference) 4/ They are not effected by the environment (unlike some morphological traits) 5/ Since mutations generally occur as random events with specific probabilities, the number of mutations can be used to calibrate evolutionary time (molecular clocks) Disadvantages ?

11. Transition A G Transversion Transition C T Transitions and Transversions in nucleotide substitutions Transitions replace a purine base with the other purine base, or a pyrimidine base with the other pyrimidine base Pyrimidines T  C C  T Purines A  G G  A Transversions replace a purine with a pyrimidine or vice versa T  A T  G C  A C  G A  T A  C G  T G  C Transition mutations are about 2 x more common than transversions

12. Mutation in Coding vs Noncoding DNA A substantial part of the DNA of eukaryotes is noncoding- introns, repetitive sequences, pseudogenes Mutations in noncoding DNA do not generally effect phenotype and therefore are not subjected to selection Some mutations in coding regions do not change amino acid sequence because of the degenerate codon system Some mutations in coding regions change amino acid sequence to a similar type of amino acid, therefore having little or no effect on protein function

13. Substitutions in Coding regions Synonymous vs nonsynonymous substitutions Synonymous substitutions are those that do not change the amino acid that is specified by the gene CUU ----> CUC = Leucine -----> Leucine Nonsynonymous substitutions are those that change the amino acid chain specified There are various degrees of nonsynonymous mutations depending on there effect on protein function. When the mutation changes the amino acid to a similar type then function may be little effected. Some amino acids of proteins are more important than others- active sites for example. CUU ----> AUU = Leucine -----> Isoleucine

14. Substitutions in Coding regions Miss-sense substitutions Miss-sense substitutions are those that prematurely terminate the gene UAU ----> UAG = Tyrosine -----> Stop UUA ----> UAA = Leucine -----> Stop Generally rare since nearly always involved change in protein activity

15. Codon usage Second Letter First Letter

16. Synonymous mutations are more commonly fixed in evolution Synonymous mutations Nonsynonymous mutations

17. Different types of sequence evolve at different rates Fourfold degenerate sites Twofold degenerate sites Downstream regions Non-degenerate sites Animal mtDNA Pseudogenes Upstream regions Introns

18. Sequence 1 Sequence 2 leu arg phe cys ser ser arg ser leu phe cys ser arg ser leu arg phe cys ser arg Sequence 1 Sequence 2 leu gap phe cys ser ser arg Sequence 1 Sequence 2 Sequence 3 Sequence 4 Sequence 5 Sequence 6 leu arg phe cys ser ser arg leu gap phe cys ser phe arg leu gap phe cys ser phe arg leu arg ile cys ser ser arg leu arg ile cys ala ser arg ile leu arg phe cys ser arg Comparing amino acid sequences

19. Sequence 1 Sequence 2 Sequence 3 Sequence 4 Sequence 5 Sequence 6 leu arg phe cys ser ser arg leu gap phe cys ser phe arg leu gap phe cys ser phe arg leu arg ile cys ser ser arg leu arg ile cys ala ser arg ile leu arg phe cys ser arg Comparing amino acid sequences Sequence Number Differences Similarities

20. Cytochrome C- a highly conserved gene Hydrophobic side chains Acidic side chains Basic side chains

21. A molecular clock for Cytochrome c Angiosperms vs animals Yeast vs mould Insects vs vertebrates Mammals vs reptiles Amino acid substitutions (per 100 residues) in cytochrome c Birds vs reptiles Fish vs land vertebrates Amphibians vs birds and mammals Birds vs mammals Time since divergence (millions of years)

22. The Neutral Theory of molecular evolution Most mutations are either selectively neutral or nearly so. Thus, the genetic variation within species results from random genetic drift Consider population of size N with a neutral mutation rate at a locus of  mutations per gamete per generation No. of new mutations =  x 2N Probability of fixation by genetic drift = frequency, p = 1/2N Number of new mutations per generation that are likely to become fixed by genetic drift = no. of mutations x probability of fixation = 

23. Molecular clocks The rate of fixation of neutral mutations is equal to the neutral mutation rate Thus, sequences diverge in evolution at a constant rate Thus, the divergence between two sequences can be used to say when the two organisms diverged from each other • But remember • Not all mutations are neutral • Not all loci change at the same rate • Transitions are more common than transversions • Rates are strictly based on generations (not years), and reproductive rates vary between species Therefore, all molecular clocks need calibrating

24. Calibration of -globin molecular clock Divergence of humans from other species based on -globin molecular clock calibrated on fossil evidence of divergence from cows 600 Shark Carp 500 Frog 400 Million years ago Chicken 300 Alligator 200 Cow Quoll 100 Baboon 0 Species Divergence based on molecular clock Divergence based on fossil record