Sex ratio adjustment and kin discrimination in malaria parasites

Abstract

Malaria parasites and related Apicomplexans are the causative agents of the some of the most serious infectious diseases of humans, companion animals, livestock and wildlife. These parasites must undergo sexual reproduction to transmit from vertebrate hosts to vectors, and their sex ratios are consistently female-biased. Sex allocation theory, a cornerstone of evolutionary biology, is remarkably successful at explaining female-biased sex ratios in multicellular taxa, but has proved controversial when applied to malaria parasites. Here we show that, as predicted by theory, sex ratio is an important fitness-determining trait and Plasmodium chabaudi parasites adjust their sex allocation in response to the presence of unrelated conspecifics. This suggests that P. chabaudi parasites use kin discrimination to evaluate the genetic diversity of their infections, and they adjust their behaviour in response to environmental cues. Malaria parasites provide a novel way to test evolutionary theory, and support the generality and power of a darwinian approach.

Figure 1. The fitness consequences of sex ratio variation

The relationship between sex allocation (given as proportion male) and fitness (given as log(ookinete production)) varies in the manner predicted by theory, revealing that this life-history trait of malaria parasites is important and under selection. Shown is log-transformed mean ookinetes (×10⁶ ml⁻¹) produced in 19 cross-factored sets of P. berghei cultures spanning 0–100% males (R²=0.77); dashed line is the fitted relationship . As expected, no ookinetes were produced in our control groups of 0% and 100% males, and we excluded these data from our analysis. Error bars, ±s.e.m.

Figure 2. Genetic variation in patterns of sex allocation

P. chabaudi genotypes exhibit significant genetic variation in the sex ratios produced throughout their infections. Genotypes DK, CW and CR all followed significantly different sex allocation patterns but AS, AJ and ER could be grouped together. Here, and in Figs 4–6, sex ratio is given as proportion male. The means from 30 independent infections are presented and the x-axis is jittered for clarity. Error bars, ±s.e.m.

Figure 3. Explaining sex ratio variation throughout infections

Sex ratios (arcsin square-root transformed) of P. chabaudi correlate with the density of: a, red blood cells; b, parasites; and c, gametocytes. Lines are fitted from the estimates predicted by the minimal model using infection parameters observed 48 h before sex ratios (see Supplementary Information). Genotypes are grouped according to the four different sex ratio patterns followed throughout 30 independent infections (Fig. 2).

Figure 4. Sex ratio varies with the genetic diversity of P. chabaudi infections

Infections with six genotypes produced significantly less female biased sex ratios than those with one genotype, but only at the start of infections. Means are presented from 40 independent infections. Error bars, ±s.e.m.

Figure 5. Sex ratios of focal genotypes during the growth phase of infections

Mean sex ratios throughout the growth phase of infections for P. chabaudi focal genotypes when alone (dashed line) and co-infecting with a second genotype (solid line). a, AS; b, AJ; c, ER. Sex ratios of genotypes AS and ER could be distinguished from sex ratios of AJ but AS and ER could not be distinguished from each other (see Supplementary Information). Sex ratios produced by AJ when co-infecting with AS or ER were not significantly different so these infections are grouped. We followed 5 independent infections for each genotype combination. Error bars, ±s.e.m.

Figure 6. Sex ratios of focal genotypes during the post-peak phase of infections

As Fig. 5 but for the post-peak phase.