Gene and species tree reconciliation(β-globin and SERA genes)Statistics 246 Spring 2006Week 7 Lecture 12Homologs Recall that homologous genes or proteins result fromSpeciation (orthologs): when separate lineages divergefrom a common ancestor and experience differentevolutionary pressure, orDuplication (paralogs): when part of a gene, a full gene,or a group of genes are duplicated within a species andthe duplication becomes fixed in the population.Subsequent evolution of the new copy or copies maydiffer from that of the original, e.g. one copy may takeon a new or more specialized function.In our discussion so far, we have seen trees with allorthologs (β-globins) or all paralogs (globins generally).Now let’s see them together, and consider the questionof determining which is which.3How we envision it happeningSpecies 1Species 2Species 4Species 34Reduction to a gene treeSpecies 1Species 2Species 4Species 3(sp.1)(sp.2)(sp.3)(sp.4)(sp. 3)(sp.4)(sp.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.5Homologs: unrecognized paralogySpecies 1Species 2Species 4Species 3(sp. 1)(sp. 3)(sp. 4)(sp. 4)(sp. 4)(sp.2)(sp. 3)Suppose that certain homologs are lost or not yet found, and that sp. 2only appears once, as above. We will think red 2 and red 3 are orthologs.6ReconciliationA reconciliation is a map between a gene tree and a species treewith gene duplications and losses being postulated to explain anyincongruence between the trees.7AlgorithmLet S and G denote the set of nodes of the speciestree and gene tree. (Both trees are assumed to berooted and binary.) For g∈G, define σ(g) to be theset of species contained in the subtree that beginsat node g. For s∈S define σ(s) similarly.A map from G to S: for every g∈G, let M(g) be thelowest (most recent) s∈S for which σ(g)⊆σ(s).For any internal g∈G, with child nodes g1 and g2, weinfer that g represents a duplication event if andonly if M(g) is equal to either M(g1) or M(g2) i.e. ifthe node g maps to the same position in thespecies tree as one (or both) of its children.8{σ(s):s ∈ S} and {σ(g):g ∈ G}9Reconciliation mapping M:G → S10Inferred 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.11Inconsistencies between S and Gcan be resolved in the same way.12Inconsistencies between S and G13Inconsistencies between S and GInserting lost or not yet found genes reconciles the two trees.14Vertebrate β-like globin genes(with a focus on mammals) The human β-like globin cluster has 5 active globin genes:embryonic ε-globin, two fetal γ-globins, the adult δ-globin andthe abundant adult β-globin. Chickens also have a β-like cluster, with ρ-globin and ε-globinat the ends, and two β-globin in between, one β expressedat hatching and the other in adulthood. Given that the avian ρ-β-ε and the eutherian ε-γ-δ-β geneclusters were the only known clusters in these taxa, it wasnatural to suppose that they were orthologous. That turnedout to be wrong!15Vertebrate β-like globins: cont. In 2001 the marsupial ω-globin was discovered. This genewas a component of a novel haemoglobin found in the bloodof neonatal tammar wallabies, expressed just before andafter the birth of the joey. The figure which follows describes the view that the ω isorthologous to the avian ρ-β-ε, and that its orthologue ineutherian mammals has been lost. The slides after thatsummarize the evidence for this conclusion.We present the picture from 2001-2004, and then present adiscovery from 2005.16The story in 2004(after Wheeler et al 2001)17(Edited) gene treefor many β-globinsSpeciesXlaev = a frog (outgroup)Oposs = grey short-tailed opossumDunn = fat-tailed dunnartMouseHum = humanEchidnaPlatyp = platypusTamm = tammar wallabyChick = chickenDuck = a likely gene duplication event as the same spp appear in both daughter lineages (and the spp tree is respected)18Species tree usedMissingDunnart: a marsupialEchidna: a monotremeDuck: a bird (avian)19Gene tree followingreconciliation withspecies treeBox means aduplication eventNo box means aspeciation event(here birds-mammals)Warning: this reconstructionmay not be true in every detail,but we think the main branchesare correct.Grey means lostor not yet foundproto-εproto-ββε-typeω-type`Lost #2Just found!Lost #120The story in 2006(after work of Vidushi Patel)Duplication predates the split ofmonotremes and marsupials21AcknowledgementsTracey Wilkinson, Florey/WEHIVidushi Patel, ANUToby Sargeant, WEHIRichard Bourgon, UCB22Selected referencesMolecular evolutionM. Nei (1987) Molecular evolutionary genetics. Col.UPW-H Li (1997) Molecular evolution. SinauerR.D.M. Page (1998) GeneTree: comparing gene and species phylogenies usingreconciled trees. Bioinformatics 14 819-820.J. Felsenstein (2004) Inferring phylogenies. SinauerGlobins in generalRE Dickerson and I Geis (1983) Hemoglobin: Structure, Function, Evolution, andPathology. Benjamin/Cummings.R Hardison (1998) Hemoglobins from bacteria to man: Evolution of different patterns ofgene expression. J Exp Biol 201:1099-1117Recent work on globins, seeWheeler et al, J Molecular Evolution (2004) 58:642-52Cooper et al, J Molecular Evolution (2005) 60:653-64…..and references therein.Evolution of the SERA gene family inPlasmodium24Overview Introduction to malaria, Plasmodium, and SERA Gene tree inference GC content Homology: paralogs vs. orthologs Reconciling gene and species trees Modifications suggested by reconciliation Predictions25Malaria Approximately 40% of the world's population is atrisk of malaria. It is found throughout the tropicaland sub-tropical regions of the world. Malaria causes more than 300 million acuteillnesses and at least one million deaths annually.Ninety per cent of deaths due to malaria occur inAfrica, south of the Sahara — mostly among youngchildren. The disease was once more widespread but it wassuccessfully eliminated from many countries withtemperate climates during the mid 20th century.26Malaria’s scope, 1999Disappeared, eradicated, or never existedLimited riskMalaria transmission occurs27The Plasmodium parasiteFour species of the Plasmodium parasite areresponsible for malaria in humans:P. vivaxP. malariaeP. ovaleP. falciparum.P. vivax and P. falciparum are the most common,and P.
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