Gametocyte sex ratios as indirect measures of outcrossing rates in malaria

Abstract

The frequency of recombination between unlike genotypes is central to understanding the generation of genetic diversity in natural populations of malaria. Here we suggest a way of investigating the problem which could complement conventional biochemical approaches to the population genetics of malaria. Sex allocation theory is one of the most successful areas of evolutionary biology. A well-supported prediction is that progressively less female-biased sex ratios are favoured with more outcrossing; equal numbers of males and females being evolutionarily stable in randomly mating outbred populations. We present a simple game theory model to support the idea that outcrossing rates in malaria will be correlated with the sex ratio of gametocytes in the peripheral blood of vertebrate hosts. Blood films from epidemiological surveys and culture-adapted isolates from Madang Province, Papua New Guinea, were used to estimate average gametocyte sex ratio of Plasmodium falciparum in the area. The geometric mean proportion of males in the population was 0.18 (95% confidence limits: 0.15-0.22). From our model, we estimate that, on average, 36% of zygotes are the result of outcrossing. This estimate assumes that most microgametes released following exflagellation are capable of fertilization. If, on average, fewer than about 70% of microgametes are capable of fertilization (as is the case in at least one other species of Plasmodium), the observed sex ratio would be consistent with between zero and 36% of zygotes being the result of outcrossing. These estimates suggest that there is usually a numerically dominant genotype in the gametocyte population in a blood meal, and that a considerable amount of selfing is occurring in P. falciparum populations in the Madang region, even though it is an area of intense year-round transmission.

Plasmodium falciparum gametocyte carriage, sex ratios and asexual parasite rates in Nigerian children before and after a treatment protocol policy change instituting the use of artemisinin-based combination therapies

“…The gametocyte sex ratio of 0.20-0.21 suggests, theoretically, that this is the maximum degree of female bias expected if the average number of viable gametes released after exflagellation by one male gametocyte was four (Read et al 1992. The population sex ratio in this endemic area is similar to that reported in neighbouring Cameroon [0.217 (Robert et al 1996)], but it is lower than the 0.346 reported in Senegal (Robert et al 2003).…”

Population genetic structure of Plasmodium falciparum in the two main African vectors, Anopheles gambiae and Anopheles funestus

“…Read et al (40) estimated from observations of gametocyte sex ratios in the peripheral blood of patients from Madang in Papua New Guinea that 62% of all P. falciparum matings are between genetically identical gametes. Based on evidence from oocyst genotyping using antigen-coding loci, overall inbreeding coefficients were estimated to be 0.90 in Papua New Guinea (18) but 0.34 in Tanzania (17).…”

Effect of gametocyte sex ratio on infectivity of Plasmodium falciparum to Anopheles gambiae

“…Considering only Plasmodium fal ciparum^ both gametocyte density (Boy d , 1949) and the sickle cell trait status of gametocyte carriers (R obert et a l., 1996) increase infectivity, those acting negatively in clude specific and non-specific transmission blocking factors (S i n d e n & Sm a l l e y , 1976; M u l d e r et a l, 1994). Despite the sexual reproduction of P. falciparum in the midgut of mosquitoes, the sex ratio of gametocytes has generally not been considered a factor influencing infec tivity to mosquitoes (B o u d in et a l, 1989;Read et al, 1992; N o d e n et a l, 1994). Bo y d et a l (1935) were appar ently alone in suggesting that variations in sex ratio, per haps due to variations in microgametocyte densities, might affect the infectivity of gametocyte carriers.…”