Why are male malaria parasites in such a rush?: Sex-specific evolution and host-parasite interactions

Abstract

Background: Disease-causing organisms are notorious for fast rates of molecular evolution and the ability to adapt rapidly to changes in their ecology. Sex plays a key role in evolution, and recent studies, in humans and other multicellular organisms, document that genes expressed principally or exclusively in males exhibit the fastest rates of adaptive evolution. However, despite the importance of sexual reproduction for many unicellular taxa, sex-biased gene expression and its evolutionary implications have been overlooked.

Methods: We analyse genomic data from multiple malaria parasite (Plasmodium) species and proteomic data sets from different parasite life cycle stages.

Results: The accelerated evolution of male-biased genes has only been examined in multicellular taxa, but our analyses reveal that accelerated evolution in genes with male-specific expression is also a feature of unicellular organisms. This 'fast-male' evolution is adaptive and likely facilitated by the male-biased sex ratio of gametes in the mating pool. Furthermore, we propose that the exceptional rates of evolution we observe are driven by interactions between males and host immune responses.

Conclusions: We reveal a novel form of host-parasite coevolution that enables parasites to evade host immune responses that negatively impact upon fertility. The identification of parasite genes with accelerated evolution has important implications for the identification of drug and vaccine targets. Specifically, vaccines targeting males will be more vulnerable to parasite evolution than those targeting females or both sexes.

Keywords: Plasmodium; gene expression; host–parasite coevolution; sex-specific selection.

Figure 1.

Stage-specific rates of evolution. Estimated as d_N/d_S, for genes expressed in sexual (male, female) and asexual blood stage malaria parasites. (A) Pattern of ‘stage-specific’ expression of genes based on proteomes of P. berghei sexual and asexual blood stages. Red represents the total number of proteins identified in each proteome. Proteins are subdivided into putative membrane and non-membrane proteins. Numbers inside the circles refer to the number of putative non-membrane proteins (solid background) and putative membrane proteins (shaded background) detected exclusively in proteomes of Males, Females, Asexual Stages or detected in all three stages (All Stages). (B–D) Rates of evolution determined by comparing genes from each closely related pair of Plasmodium species. The genes used for this analysis are the orthologs of the P. berghei genes identified in (A). P. berghei and P. yoelii (B); P. falciparum and P. reichenowi (C); P. vivax and P. knowlesi (D).

Figure 2.

Stage- and location-specific rates of evolution. Estimated as d_N/d_S, for predicted non-membrane (solid bars) and membrane (shaded bars) proteins expressed in sexual (male, female) and asexual blood stage malaria parasites. Genes were classified according to their exclusive detection in P. berghei proteomes of Males, Females, Asexual Stages or All Stages (see Fig. 1), The rates of evolution were determined by comparison of genes of the following pairs of Plasmodium species: P. berghei and P. yoelii (A); P. falciparum and P. reichenowi (B); P. vivax and P. knowlesi (C).

Figure 3.

The strength of diversifying selection. Estimated as p_N/p_S, for P. falciparum proteins with (solid bars) or without predicted immune epitopes (shaded bars) expressed in sexual (male, female) and asexual blood stage malaria parasites. (A) Percentage of proteins containing immune epitopes identified from the Immune Epitope Database and Analysis Resource. Genes were classified according to their exclusive detection in P. berghei proteomes of Males, Females, Asexual Stages or All Stages (see Fig. 1). The strength of diversifying selection on P. falciparum predicted non-membrane (B) and membrane (C) proteins.