Fig. 4.

Networks of ADR genes and their SL partners extracted from the inferred Plasmodium SL genes. Plasmodium SL gene pairs were inferred from yeast SL pairs. In this network, nodes represent genes and the link between them indicates an SL interaction. When both are simultaneously mutated, an SL condition is satisfied. Gene conservation between Plasmodium and yeast can be categorized into two types of relations. The simplest case is a one-to-one relation between Plasmodium and yeast genes (orthologous relation). However, duplication events during evolution cause a one-to-n relation in which two or more yeast genes are homologous to one Plasmodium gene. (A) For example, the one-to-one case corresponds to one yeast gene having one Plasmodium homolog; the SL pairs Y1 and Y2 correspond to SL pair P1 and P2. In the one-to-n case, several yeast genes have the same Plasmodium homolog; SL pairs Y1 and Y2 can correspond to only one gene between P1 and P2. In this case, an autolink (auto-loop) is formed in the network. (B) For yeast SL networks represented by Y3, Y4, and Y5, various relations such as one-to-one, n-to-one, auto-loop, and SL pair-containing auto-loop genes can be combined. (C) Networks of the four inferred ADR genes in the Plasmodium species. When two SL yeast partners are phylogenetically related to a single Plasmodium gene, an auto-link appears in the SL network. Single gene targeting is possibly more dangerous than double gene targeting. Therefore, we eliminated the auto-loop nodes from the drug target candidates and denoted them as red X’s. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)