SEX DETERMINATION AND SEX DIFFERENTIATION IN MALARIA PARASITES
Authors: CORNELISSEN ALBERT W. C. A. 
Published: January 2008

1. The most coherent body of information on the malarial life‐cycles comes from studies on P. berghei and P. falciparum. For both species there is an extensive and accurate description of the life‐cycle available based on synchronized in‐vitro and in‐vivo infections (the latter only for P. berghei).

2. The trophozoites preceding the young gamonts are already sexually differentiated, that is, they are micro‐ and macrogamontoblasts. They are, however, morphologically indistinguishable from the asexual trophozoites which will develop into meronts. This is in contrast with the gamontoblasts of the closely related eimerian species, which are already morphologically differentiated at this stage of their sexual development.

Experiments with synchronized P. berghei infections suggest that the induction towards asexual or sexual development of intra‐erythrocytic parasites occurs between 8–12 h after erythrocyte invasion.

3. DNA measurements by direct fluorometry of individual Feulgen‐stained stages of P. berghei and P. falciparum, has shown that all stages are haploid, except for the zygote. Hence, meiosis occurs within the zygote. The latter has been confirmed in EM studies of ookinete (zygote) development of P. berghei within its mosquito vector.

4. EM studies also provided evidence for the fact that the malarial genome is organized in 10–14 chromosomes, which is in line with the estimates based on PFG analysis of molecular karyotypes of different malarial species.

5. Infections with clones of the asexual intra‐erythrocytic stages resulted in the formation of both micro‐ and macrogamonts. Since these asexual stages are haploid, gamonts develop from genetically identical cells and their development must be due to selective gene expression. How many genes are involved in this process, how they are induced and regulate differentiation is still an open question.

6. Macrogamonts contain an extra amount of nuclear DNA in excess of the haploid value. Roughly the same amount of extra DNA is still present in the zygote, indicating that it is probably due to a selective amplification of certain genes or repetitive sequences. No indications have been found for an amplification of rRNA genes in macrogamonts or in cloned lines of Plasmodium parasites producing high numbers of infective macrogamonts.

7. Mature microgamonts possess DNA values between 1C and 2C and are not octaploid as has been generally accepted. DNA replication in microgamonts, necessary for the production of the 8 microgametes, starts at the activation of the microgamont. During this process, microgamonts perform three mitotic divisions in which they replicate their entire genome in about 3 min. It is assumed that microgamonts activate simultaneously approximately 1300 replication origins to enable such a fast genome replication. Direct evidence for this hypothesis in the form of direct ultrastructural evidence of DNA molecules of replicating microgamonts is, however, lacking.

8. In‐vitro fertilization of macrogametes of P. berghei takes place within 1 h of gametogony. The formed zygote (2C) immediately starts to synthesize DNA and within 3 h a tetraploid value is reached. Thereafter, DNA synthesis ceases for at least 21 h. EM studies of this process in vivo showed that synaptonemal complexes are formed at 25 h after fertilization. Taken together, these results strongly indicate that genome duplication precedes the first meiotic division, i.e. meiosis in Plasmodium follows the normal eukaryotic pattern. Thus, as expected Plasmodium shows recombination between genes determining characters such as enzymes, antigens, drug resistance and virulence.

9. DNA synthesis in malaria parasites is regulated by a DNA polymerase‐a like enzyme that differs in some respect in the corresponding enzyme of the host and this could become a target for chemotherapeutic control of the parasite life‐cycle.