Phylogenetic trees: Computer models of evolution Dr Dan Everett CSCI 1210

Gene sequence and active sites  This diagram represents the amino acid sequence of the gene for Yeast Ubiquitin Activating Enzyme, UBA-1  Colored regions are conserved – no random mutations observed

Triosephosphate Isomerase Spinach CNGTKESITKLVSDLNSATLEAD Rice CNGTTDQVDKIVKILNEGQIAST Monkey MNGRKQNLGELIGTLNAAKVPAD Human MNGRKQSLGELIGTLNAAKVPAD MosquitoMNGDKASIADLCKVLTTGPLNAD

Sequence differences  The sequences are peptides, not DNA codons  The sequences must be aligned to correct for insertions and deletions (hard problem)  Monkey vs. human proteins show fewer differences than spinach vs. rice

Sequence distance matrix SpinachRiceMosquitoMonkeyHuman Spinach Rice Mosquito Monkey Human

First step in the tree construction  Humans and monkeys are most closely related of all pairs of species in the table.  Create an initial subtree. (Hypothetical common ancestors in green)

Revised distance matrix: SpinachRiceMosquitoPrimate Spinach Rice Mosquito Primate

Second subtree:

Revised distance matrix, again SpinachRiceAnimal Spinach Rice Animal

The Final tree…

Why this result is significant…  Before DNA techniques, biologists constructed phylogenetic trees using traditional tools (fossils, anatomy, etc)  DNA tools provide an independent method for constructing phylogenetic trees  Trees constructed with different methods match quite well!

A common human ancestor…  Can the scenario on the right happen?  Can the scenario on the left happen?  M1 must be smaller than H!

… must exist! But when and where?

Mitochondrial DNA  Mitochondria are the “energy factories” of the cell  Mitochondria float in the cytoplasm  They have their own DNA and reproduce independently of the cell nucleus  Passed by mother to child in the egg  Not subject to sexual recombination, so simpler to track

The “Out of Africa” Hypothesis  This phylogenetic tree constructed using mitochondrial DNA from 145 humans  Consistent with migration of original humans from Africa  Numbers represent thousands of years since common ancestor

“Mitochondrial Eve”  Existed about 200,000 years ago in Africa  Was the common female ancestor of all living humans  Was NOT the only living female at the time!  Use mitochondrial DNA because we inherit it from our mothers only Rebecca Cann et al, Nature 1987

Critique of “Mitochondrial Eve”  Rates of ‘neutral’ mutation are not constant  In some cases mitochondrial DNA has combined with nuclear DNA from the father  Do these problems invalidate the theory?

Acknowledgements Human family tree: Dr Curtis Strobeck, University of Alberta  ads/winter03/lecture/b1/curt_strobeck/public/lectures /Lecture_26_Tree_of_Individuals.pdf ads/winter03/lecture/b1/curt_strobeck/public/lectures /Lecture_26_Tree_of_Individuals.pdf ads/winter03/lecture/b1/curt_strobeck/public/lectures /Lecture_26_Tree_of_Individuals.pdf  UAB-1 gene sequence: students/ub/e1.html  Phylogentic tree computation example: Gaston Gonnet,  Institute for Scientific Computing  Zurich, Switzerland