Malaria parasites exhibit extensive variation throughout their infections, in both investment in gametocytes and their sex ratio. Furthermore, malaria parasites alter these behaviours in response to changes in their in-host environment. One of our aims is to understand why such phenotypic plasticity in reproductive strategies has evolved and under what circumstances parasites should alter their behaviour.
Adjusting investment into males and females
Throughout infections, malaria parasites show considerable variation in their allocation of resources to male and female gametocytes. Furthermore, malaria parasites facultatively alter their investment in gametocytes and their sex ratio in response to changes in host anaemia. Such variable sex ratios within infections are not predicted by classical Local Mate Competition theory.
One possible explanation is that parasites adjust their sex ratio strategy to compensate for reductions in their fertilisation success ('fertility insurance') due to a lack of males. When sex ratios are very female-biased and gametocyte density is low, or hosts are anaemic, there is a risk of too few males being taken up in blood meals to fertilise the females present. Furthermore, even if there are plenty of gametocytes, transmission-blocking immune factors could impair the ability of males to make viable gametes, and the development of such immune factors has been proposed to coincide with anaemia. Therefore, in either of these scenarios, genotypes must ensure their females are fertilised by investing in extra males (more than expected from their inbreeding rate alone). If levels of transmission-blocking immune factors and anaemia vary throughout infections, then the importance of a fertility insurance strategy will co-vary. In essence, fertility insurance theory simply predicts lower female bias, for a given inbreeding rate, than classical Local Mate Competition theory.
Whilst we are yet to experimentally test this theory, our data from P. chabaudi are supportive; more males are produced when gametocyte and red blood cell densities are low and reticulocyte density is high.
Adjusting investment into gametocytes
Evolutionary theory assumes that parasites must balance their resource allocation between asexual replication and investment in gametocytes. Parasites must maximize their in-host survival in the face of attack from the immune response, competition and resource limitation, and theory predicts that success in this endeavour is correlated to parasite numbers. At the same time, parasites must maximize opportunities to transmit to vectors by producing gametocytes, which requires investment into reproduction. Theory predicts that intermediate levels of investment in growth are favoured by natural selection; high investment occurs at the expense of transmission and increases the risk of host death, but low investment incurs the risk of parasite being cleared by hosts and results in poor transmission.
However, investment in gametocytes is not a simple function of asexual population density and this trait is altered by changes factors such as host anaemia. Our data supports the idea that parasites may be responding to levels of anaemia simply because anaemia determines the availability of preferred red blood cells. Different malaria parasite species specialize in invading red blood cells of different ages, so when preferred red blood cells are scarce parasites may also have to resolve another trade-off between using available cells for asexual replication or gametocytes.
When preferred red cells are scarce, parasites may not be able to afford to increase investment in gametocytes but can alter the sex ratio of gametocytes they produce - in this case they should invest in more males relative to females. This is supported by our data showing that rodent malaria parasites have different response to experimentally induced anaemia: P. chabaudi can use reticulocytes and increases investment in gametocytes but P. vinckei cannot use reticulocytes and increases investment in males.