Mutation – a change in the nucleotide sequence of the geneticmaterial of an organism – is the underlying force of evolution. •Mistakes during replication •Chemical Changes in the nucleic acids •UV – dimerization •Spontaneous decomposition – base changes •Chemical/physical changes at the chromosome level •Radiation (X-ray/Gamma) – double-strand breaks •Sexual reproduction (polyploidy)
Lecture 1 More than 200gene families arecommon to all life. Most of these “orthologous genes” are essential.
Lecture 1But how do they do this whenmost mutations tend to mess things up more than they improve them?
They must find a way to break free from the oppression of natural selection
Lecture 1Duplication events Retroviruses Horizontal Gene Transfer - genes can be transferred between organisms both in the laboratory, and in nature.
hCYP3A Locus Chromosome-7 ~80% Homology 40 Kb 4 Kb 5 Kb P2 P1 3A43 3A4 3A7 3A5 43cDNA 4cDNA 7cDNA 5cDNA All have roughly 90% homology in the first 1000 bp of their promoters.Finta & Zaphiropoulos, 2000 Gellner et al., 2001
Lecture 1Eukaryotes often have pseudogenes,duplicated genes that have accruedmutations that render them inactive, intheir genomes. Mutated regulatory elements, frame shifts, addition/loss of stop codons, lost splice sites, deleterious mutations, etc.
Lecture 1We make assumptions when we do this… •Evolution is real - members of a group share a common evolutionary history, and are "closely related," more so to members of the same group than to other organisms. •Bifurcation - new kinds of organisms may arise when existing species or populations divide into exactly two groups. •Organisms change over time – closely-related groups are share synapomorphies, unique features not present in more distant ancestorsAnd even more when we use gene sequences… •Mutations are a “one-way” street •We can assign a “value” for every base-pair mutated •“horizontal gene transfer” has not occurred among the orthologues.
Lecture 1 The identification and characterization of gene orthologues helps us in ever expanding ways:1. Enhanced discovery • By finding regions that are highly conserved, primers can be designed to discover orthologues from new species2. Accelerated science • We can compare gene sequences and hint at their function, expression patterns, etc.3. More powerful experiments • We can plan methods to genetically engineer just about anything4. GAAATAACA and Pharmacogenomics • We can peer into our own genomes and predict certain diseases and the success of many treatments