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Introduction to Molecular Evolution Level 3 Molecular Evolution and Bioinformatics Jim Provan Page and Holmes: Chapter 1 Complete genome sequences 1.83 Mbp (1995) 12 Mbp (1996) 1.66 Mbp (1996) 106.3 Mbp (2000) 3300 Mbp (2001) Complete genome sequences DNA sequences are valuable because they provide the most detailed anatomy of an organism Much of modern biology relies on unravelling information stored in gene sequences Importance of molecular evolution as a science: Gene sequences represent an invaluable document of the history of life on earth How do we recover and interpret this information? The tree of life – pre 1970s style! vs. Prokaryotes Eukaryotes The tree of life – post 16S rRNA style! Green non-sulphur Gram- bacteria positives Purple bacteria Cyanobacteria Flavobacteria Thermotogales Methanosarcina Halophiles Methanobacterium Methanococcus T. celer Thermoproteus Pyrodictium Animals Slime moulds Entamoebae Fungi Plants Ciliates Flagellates Trichomonads Microsporidia Diplomonads More recent evolution Dentist Patient C Patient A Patient G Patient B Patient E Patient A Dentist LC 2 LC 3 Patient F LC 9 LC 35 LC 3 Patient D Milestones in the study of molecular evolution Early this century, George Nuttal mixed sera and antisera from different species to determine “blood relationships”: Idea was that more closely related species would exhibit strongest cross-reactions between sera and antisera Displayed that degree of similarity between genes reflects strength of evolutionary relationship between tham Despite advances in theoretical evolutionary biology (“neo-Darwinian synthesis”), the study of molecular evolution made little progress in the next fifty years due to a lack of data Milestones in the study of molecular evolution In 1953, James Watson and Francis Crick proposed the doublehelical model of the structure of DNA This revealed the mechanism by which DNA carried hereditary information between generations Milestones in the study of molecular evolution In 1955, Fred Sanger and colleagues sequenced the first protein, insulin: Sequences were obtained for cattle, pigs and sheep Three amino acid differences showed genetic variation alongside morphological variation Next stage was to build models of molecular evolution: Basic models assumed that evolution was largely a stochastic process Also realised that with a limited number of bases and amino acids, observed change may not represent actual change Controversial theory that mutations occurred at regular intervals: the “molecular clock” Milestones in the study of molecular evolution Commonly held view on human origins was that humans were genetically distinct from great apes Work of Sarich & Wilson (1967) changed this view: Cross-reacted serum albumin between primates Demonstrated that human, gorilla and chimpazee were genetically equidistant and distinct from orang-utan Calibrated molecular clock Chimpanzee Gorilla Orang-utan Human Sivapithecus Ramapithecus Divergence time > 15Myr ago Chimpanzee Divergence time ~5Myr ago Gorilla Old World monkeys ~30MYr ago Human Orang-utan Sivapithecus Ramapithecus Old World monkeys ~30MYr ago Milestones in the study of molecular evolution Real “explosion” of information on molecular evolution since the advent of PCR: Nucleotide sequences have replaced protein sequences Can sequence DNA from samples thousands of years old Major advances in evolutionary theory What this course will cover Architecture and organisation of the genome Evolution of proteins Phylogenetics Evolution of natural populations Organelle genome evolution Bioinformatics Tools Practical applications
