MBE Advance Access published online on August 11, 2004
Molecular Biology and Evolution, doi:10.1093/molbev/msh228
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2004; all rights reserved
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1 Department of Statistics, University of California, Berkeley, USA
* To whom correspondence should be addressed. E-mail: terry{at}stat.berkeley.edu.
Plasmodium falciparum is the parasite responsible for the most acute form of malaria in humans. Recently, the serine repeat antigen (SERA) in P. falciparum has attracted attention as a potential vaccine and drug target, and has been shown to be a member of a large gene family. In order to clarify the relationships among the numerous P. falciparum SERAs, and to identify orthologs to SERA5 and SERA6 in Plasmodium species affecting rodents, gene trees were inferred from nucleotide and amino acid sequence data for 33 putative SERA homologs in 7 different species. (A distance method for nucleotide sequences which is specifically designed to accommodate differing GC content yielded results which were largely compatible with the amino acid tree. Standard distance and maximum likelihood methods for nucleotide sequences, on the other hand, yielded gene trees which differed in important respects.) In order to infer the pattern of duplication, speciation, and gene loss events in the SERA gene family history, the resulting gene trees were then "reconciled" with two competing Plasmodium species tree topologies which have been identified by previous phylogenetic studies. Parsimony of reconciliation was used as a criterion for selecting a gene tree/species tree pair, and provided (i) support for one of the two species trees and for the core topology of the amino acid-derived gene tree, (ii) a basis for critiquing fine detail in a poorly resolved region of the gene tree, (iii) a set of predicted "missing genes" in some species, (iv) clarification of the relationship among the P. falciparum SERA, and (v) some information about SERA5 and SERA6 orthologs in the rodent malaria parasites. Parsimony of reconciliation and a second criterion--implied mutational pattern at two key active sites in the SERA proteins--were also seen to be useful supplements to standard "bootstrap" analysis for inferred topologies.
Original Article
The Serine Repeat Antigen (SERA) Gene Family Phylogeny in Plasmodium: the Impact of GC Content, and Reconciliation of Gene and Species Trees
2 The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia; Swiss Institute for Experimental Cancer Research, NCCR Molecular Oncology, Bioinformatics, CH-1066 Epalinges s/Lausanne, Switzerland
3 The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia
4 Department of Statistics, University of California, Berkeley, USA; The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia
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