1 http://www.youtube.com/watch?v=ZSBq8geuJk0 2 Summary from round I ❖ Dogs. ❖ Short-legged dogs have same, VERY DISTINCT (= highly unlikely) causal mutation ❖ Predict: common origin! ❖ Test: relatedness ❖ ❖ Finding: Nope. Short-legged dogs often more related to many long-legged breeds than other short-legged Now what? 3 River out of Eden* Domestication Breed creation *Title of Richard Dawkins book Ref. 4 In other pictures... Wolf gene pool: all the alleles amongst wolves 4 5 Dogs Wolf gene pool Dog gene pool 6 Breed 1 Breed 2 Breed 3 Dog gene pool 7 Recreating history ❖ The structure and specific sequence of the insertion & its target let us ‘look at’ this event from tens of thousands of years ago ❖ We will work backwards, then forwards to look backwards! 8 Meteor strike? ❖ The DNA change is not a single nucleotide (base) change ❖ It’s an insertion of ~5000 bases... of a growth-related gene! ❖ How can this happen? Where did it come from? ❖ Hint: some viruses live this way! 9 1 2 Different than flu: fuses, not engulfed 3 4 5 http://www.rkm.com.au/VIRUS/HIV/HIV-images/VIRUS-HIV-life-cycle.jpg I need to become a gene! 10 What’s in a word? ❖ Transcribe: re-write (in bio, make an RNA copy of DNA) ❖ reverse transcribe: make a DNA copy of RNA ❖ reverse transcriptase: one that does that Like… and unlike! ❖ The inserted DNA looks like another dog gene ❖ and a human one--that controls growth!!! ❖ This makes sense--another tool of hypothesis testing ❖ But its got pieces missing compared to the original?!? ❖ How can this happen? ❖ Hint: eukaryotes (which are what) make RNA this way 11 12 The splicing story content ‘commercials’ http://purpleopurple.com/inventions-and-inventors/gene-exons-and-introns.jpg Sidenote: yeah--not magic. 13 http://genesdev.cshlp.org/content/17/4/419/F1.large.jpg Picking out the pieces ‘Landing site’ of retrogene DNA (GTTA) Source of the retrogene read as “came from” Note ACA = ACA 14 Where’d that come from? 15 16 Summary ❖ Short-legged dogs have a common mutation ❖ Not from immediate ancestry ❖ ❖ Likely lost from other lineages rather than new to these Insertion is a ‘retro-gene’ for a growth factor ❖ the same growth factor gene that is altered in a common form of human dwarfism 17 How I drew it up (entire map posted with lecture) 18 Reserve/unused material 19 Losing diversity Random Each column is a subset length of DNA. Note no correlation top selected & bottom Few chromosomes Often homozygous Little opportunity for recombination Giant stretches not recombined Ref. 4 Bad words ❖ [Linkage Disequilibrium] describes the association between pairs of loci in the genome. For example, if individuals with allele A1 at locus A are significantly more likely to have allele B1 at locus B, the two loci are in linkage disequilibrium. ❖ Or: Are genes as free to wander as we’d expect? Or are they acting like they are ‘tied together’ more than predicted by physical distance 20