CS 262: Computational Genomics Spring 2002-2003 Lecture 18 Overview of Phylogeny Lecturer: Prof. Serafim Batzoglou Scribe: Gaurav Garg ([email protected]) ([email protected]) We have been talking about phylogeny throughout the course but never really looked at it in depth, so in this last lecture we intend to tie everything together by covering in a little more depth phylogeny and evolution. We believe that all life forms are connected through an evolutionary tree. Also, evolution is something we want to understand on its own regard, so in this age of high throughput genomics we hope genomics could help us unravel the various mysteries of life through sequence comparison. The figure on last page shows a small part of the evolutionary tree, of mammals, which are a tiny fraction of all the organisms on the earth. For the mammals we have a pretty good idea of what the evolutionary tree should look like e.g. we know that we are closer to monkeys than to rodents, similarly cats and dogs are closer to one another than to cows or pigs. We also believe that we are closer to the rodents in terms of evolutionary time (not sequence) than to dogs, cats or cows. But this is still a somewhat unclear question, we know pretty well but not quite 100%. In fact when we look at organisms other than mammals, like viruses, bacteria we do not have a good idea of their evolutionary relationships at all. So this motivates us for the rest of the lecture. 1. What are Phylogenies? Phylogenies are trees that show the history of life. A phylogeny tree shows the connection between various organisms and weight of the branches in the tree give an idea of time between evolutions of different organisms. A node with two edges out of it is the common ancestor through which speciation occurs, e.g. humans have a common ancestor with mice 80 million years ago. Beyond actual organisms particular sequence elements can also have their own evolution history within a genome. We have already seen selfish DNA. Selfish DNA is repeating transposable element, i.e. a selfish DNA makes a copy of it and inserts itself at a different position in the Genome. Now these elements have essentially fooled the genome into believing that it actually exists at two places within it. This can arise just like life, by chance. So if we have a DNA that transposes itself then more copies of its will transpose themselves more and in this way we get evolution of repeats. Hence within a Genome we can get a phylogeny of repeats. We can similarly have phylogeny of genes that copy themselves by duplication. Across organisms a particular gene family may have a whole history of how it evolved in the different branches of the tree. Hence we can conclude that phylogeny tries to answer the following questions. How do you establish relationships between (a) different organisms (b) between one family of elements within an organism or across organisms?Before we move further lets define the Orthologs and Paralogs. Orthologs are two elements that have diverged because of speciation whereas Paralogs are two elements that have diverged because of duplication. So if we have a gene and this gene get duplicated and make two copies of it. And say we have two organisms; mouse and rat that evolved after the duplication then each one will have two copies of the gene. The two originals (between mouse and rat) are Orthologs, the two copies (between mouse and rat) are also Orthologs but an original and copy pair (between mouse and rat) is Paralogs. So both original versions of the gene in rat and mouse have come from the same gene, and both copies have come from the same copy version. But copy version in mouse and original in rat have not come from the same sequence, but they are very similar. They have actually come from a duplication of the original sequence before. Both orthology and paralogy are together called homology. Any two similar sequences are thus homologos, unless they are similar by some stroke of luck, which is very highly unlikely. 2. Inferring Phylogenies Phylogeny trees can be inferred in many different ways e.g. by looking at the morphology of the organisms. E.g. According to morphology organisms with 4 legs could be grouped together but this is not true actually, the crocodile has 4 legs, dog has 4 legs and bat has 2 legs, but dogs are closer to bats than to crocodiles because they are mammals. So morphology cannot in general tell you a lot about the phylogeny of animals as compared to molecular methods that do a sequence comparison. Take the following example of species for which we do not know their phylogeny Orc: ACAGTGACGCCCCAAACGT Elf: ACAGTGACGCTACAAACGT Dwarf: CCTGTGACGTAACAAACGA Hobbit: CCTGTGACGTAGCAAACGA Human: CCTGTGACGTAGCAAACGA The different colors show the alignment. It is more common for dwarfs, humans and hobbits to have a similar nucleotide than for humans and orcs or humans and elves. But unlike this example it is not always easy to make this tree by the eye, so before we proceed further lets make a little background of the trees. 3. Background on Trees Each edge of the tree can have length that specifies the time of evolution, or better the effective time of evolution because some species evolve much faster than the otherspecies, e.g. rodents are believed to evolve much faster than other organisms. The tree can be rooted or unrooted in general. If the tree is unrooted than we don’t really know where the common ancestor should be placed e.g. as shown in the figure we could place the common ancestor (the root) at number of places. But there is no good way to figure out where to place this root. A tree with N leafs has 2N – 2 nodes if it is unrooted and has 2N – 1 nodes if it rooted. This is because our trees are all binary. We assume all our trees to be binary because it is very highly unlikely that at exactly the same point three different species evolved. Also, even if they did we can always convert any tree to binary tree by adding more nodes. We also label the internal nodes of the tree and a convenient way to do this is to label in such a way that of the two leaf
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