Combined phylogeny and neighborhood analysis of the evolution of the ABC transporters conferring multiple drug resistance in hemiascomycete yeasts.
BACKGROUND
Pleiotropic Drug Resistant transporters (PDR) are members of the ATP-Binding Cassette (ABC) subfamily which export antifungals and other xenobiotics in fungi and plants. This subfamily of transmembrane transporters has nine known members in Saccharomyces cerevisiae. We have analyzed the complex evolution of the pleiotropic drug resistance proteins (Pdrp) subfamily where gene duplications and deletions occur independently in individual genomes. This study was carried out on 62 Pdrp from nine hemiascomycetous species, seven of which span 6 of the 14 clades of the Saccharomyces complex while the two others species, Debaryomyces hansenii and Yarrowia lipolytica, are further apart from an evolutive point of view.


RESULTS
Combined phylogenetic and neighborhood analyses enabled us to identify five Pdrp clusters in the Saccharomyces complex. Three of them comprise orthologs of the Pdrp sensu stricto, Pdr5p, Pdr10p, Pdr12p, Pdr15p, Snq2p and YNR070wp. The evolutive pathway of the orthologs of Snq2 and YNR070w is particularly complex due to a tandem gene array in Eremothecium gossypii, Kluyveromyces lactis and Saccharomyces (Lachancea) kluyveri. This pathway and different cases of duplications and deletions were clarified by using a neighborhood analysis based on synteny. For the two distant species, Yarrowia lipolytica and Debaryomyces hansenii, no neighborhood evidence is available for these clusters and many homologs of Pdr5 and Pdr15 are phylogenetically assigned to species-based clusters. Two other clusters comprise the orthologs of the sensu lato Pdrp, Aus1p/Pdr11p and YOL075cp respectively. The evolutionary pathway of these clusters is simpler. Nevertheless, orthologs of these genes are missing in some species.


CONCLUSIONS
Numerous duplications were traced among the Hemiascomycetous Pdrp studied. The role of the Whole Genome Duplication (WGD) is sorted out and our analyses confirm the common ancestrality of Pdr5p and Pdr15p. A tandem gene array is observed in Eremothecium gossypii. One of the copies is the ortholog of Snq2 while the other one is lost in the post-WGD species. The neighborhood analysis provides an efficient method to trace the history of genes and disentangle the orthology and paralogy relationships.
Seret
Marie-Line
ML
Unité de Génétique (GENA), Université Catholique de Louvain, Louvain-la-Neuve, Belgium. marie-line.seret@uclouvain.be
Diffels
Julie F
JF
Goffeau
André
A
Baret
Philippe V
PV
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D004271:DNA, Fungal / Q000235:genetics; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics*; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000235:genetics*; D016681:Genome, Fungal; D010802:Phylogeny; D004718:Saccharomycetales / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D018528:ATP-Binding Cassette Transporters; D004271:DNA, Fungal; D005656:Fungal Proteins