Gene and species tree reconciliation globin and SERA genes Statistics 246 Week 7 Spring 2006 Lecture 1 Homologs Recall that homologous genes or proteins result from Speciation orthologs when separate lineages diverge from a common ancestor and experience different evolutionary pressure or Duplication paralogs when part of a gene a full gene or a group of genes are duplicated within a species and the duplication becomes fixed in the population Subsequent evolution of the new copy or copies may differ from that of the original e g one copy may take on a new or more specialized function In our discussion so far we have seen trees with all orthologs globins or all paralogs globins generally Now let s see them together and consider the question of determining which is which 2 How we envision it happening Species 1 Species 2 Species 3 Species 4 3 Reduction to a gene tree Species 1 sp 1 sp 2 Species 2 sp 3 sp 4 sp 3 Species 3 sp 4 sp 4 Species 4 sp 2 sp 3 sp 4 Note that when no losses occur we have copies of different parts of the species tree within the gene tree 4 Homologs unrecognized paralogy Species 1 sp 1 sp 3 Species 2 sp 4 sp 4 Species 3 sp 4 sp 2 Species 4 sp 3 Suppose that certain homologs are lost or not yet found and that sp 2 only appears once as above We will think red 2 and red 3 are orthologs 5 Reconciliation A reconciliation is a map between a gene tree and a species tree with gene duplications and losses being postulated to explain any incongruence between the trees 6 Algorithm Let S and G denote the set of nodes of the species tree and gene tree Both trees are assumed to be rooted and binary For g G define g to be the set of species contained in the subtree that begins at node g For s S define s similarly A map from G to S for every g G let M g be the lowest most recent s S for which g s For any internal g G with child nodes g1 and g2 we infer that g represents a duplication event if and only if M g is equal to either M g1 or M g2 i e if the node g maps to the same position in the species tree as one or both of its children 7 s s S and g g G 8 Reconciliation mapping M G S 9 Inferred duplications boxes We can now go on to infer genes lost or not yet found completing the part of the species tree remaining at each duplication see next slides 10 Inconsistencies between S and G can be resolved in the same way 11 Inconsistencies between S and G 12 Inconsistencies between S and G Inserting lost or not yet found genes reconciles the two trees 13 Vertebrate like globin genes with a focus on mammals The human like globin cluster has 5 active globin genes embryonic globin two fetal globins the adult globin and the abundant adult globin Chickens also have a like cluster with globin and globin at the ends and two globin in between one expressed at hatching and the other in adulthood Given that the avian and the eutherian gene clusters were the only known clusters in these taxa it was natural to suppose that they were orthologous That turned out to be wrong 14 Vertebrate like globins cont In 2001 the marsupial globin was discovered This gene was a component of a novel haemoglobin found in the blood of neonatal tammar wallabies expressed just before and after the birth of the joey The figure which follows describes the view that the is orthologous to the avian and that its orthologue in eutherian mammals has been lost The slides after that summarize the evidence for this conclusion We present the picture from 2001 2004 and then present a discovery from 2005 15 The story in 2004 after Wheeler et al 2001 16 Edited gene tree for many globins Species Xlaev a frog outgroup Oposs grey short tailed opossum Dunn fat tailed dunnart Mouse Hum human Echidna Platyp platypus Tamm tammar wallaby Chick chicken Duck a likely gene duplication event as the same spp appear in both daughter lineages and the spp tree is respected 17 Species tree used Missing Dunnart a marsupial Echidna a monotreme Duck a bird avian 18 Gene tree following reconciliation with species tree Grey means lost or not yet found type Lost 2 Just found proto proto Box means a duplication event Warning this reconstruction type may not be true in every detail but we think the main branches No box means a are correct speciation event here birds mammals Lost 1 19 The story in 2006 after work of Vidushi Patel Duplication predates the split of monotremes and marsupials 20 Acknowledgements Tracey Wilkinson Florey WEHI Vidushi Patel ANU Toby Sargeant WEHI Richard Bourgon UCB 21 Selected references Molecular evolution M Nei 1987 Molecular evolutionary genetics Col UP W H Li 1997 Molecular evolution Sinauer R D M Page 1998 GeneTree comparing gene and species phylogenies using reconciled trees Bioinformatics 14 819 820 J Felsenstein 2004 Inferring phylogenies Sinauer Globins in general RE Dickerson and I Geis 1983 Hemoglobin Structure Function Evolution and Pathology Benjamin Cummings R Hardison 1998 Hemoglobins from bacteria to man Evolution of different patterns of gene expression J Exp Biol 201 1099 1117 Recent work on globins see Wheeler et al J Molecular Evolution 2004 58 642 52 Cooper et al J Molecular Evolution 2005 60 653 64 and references therein 22 Evolution of the SERA gene family in Plasmodium Overview Introduction to malaria Plasmodium and SERA Gene tree inference GC content Homology paralogs vs orthologs Reconciling gene and species trees Modifications suggested by reconciliation Predictions 24 Malaria Approximately 40 of the world s population is at risk of malaria It is found throughout the tropical and sub tropical regions of the world Malaria causes more than 300 million acute illnesses and at least one million deaths annually Ninety per cent of deaths due to malaria occur in Africa south of the Sahara mostly among young children The disease was once more widespread but it was successfully eliminated from many countries with temperate climates during the mid 20th century 25 Malaria s scope 1999 Disappeared eradicated or never existed Limited risk Malaria transmission occurs 26 The Plasmodium parasite Four species of the Plasmodium parasite are responsible for malaria in humans P vivax P malariae P ovale P falciparum P vivax and P falciparum are the most common and P falciparum causes the most deadly type of malaria infection 27 Plasmodium and the Anopheles mosquito The Plasmodium parasite enters the human host from the saliva of an infected Anopheles mosquito Once in the human bloodstream it undergoes a series of changes
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