Sex Determination and Sex Differentiation in Malaria Parasites

Abstract

Summary 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 ...

The cell biology of malaria infection of mosquito: advances and opportunities

“…The ploidy and replication of the gametocyte genome has been a controversial topic, resolved in large part by the studies of Cornelissen and Janse in the 1980s, who, using cytochemical techniques, showed that mature gametocytes like the merozoite are haploid, and that the male cell replicated its DNA three times in brief period (∼10 min) between induction and microgamete release – exflagellation (Janse et al ., 1986a,b; Cornelissen, ). This replication is cdpk4 dependent (Guttery et al ., ).…”

“…Although this observation is entirely consistent with the absence of histone 1 from the genome, it also raises fascinating questions as to how the initial 14, and final 112, filamentous chromosomes (whose telomeres are likely embedded in the nuclear envelope) can be moved by the kinetochores on the spindle microtubules with such speed and precision without breaking. The female gamete like the originating immature female gametocyte is haploid, but the intervening nuclear events are unclear; data suggested that the DNA content may rise above 1°C (Cornelissen, ) and descriptions of spindle‐like structures in the developing (putative) macrogametocyte are either erroneous or suggest the female genome is somehow modified (Sinden et al ., ).…”

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“…The fact that both female and male can be produced by haploid bloodstage parasite, the sex of a gametocyte does not result from chromosomal differences between both types of cell but their development must be due to selective gene expression. In general, the number of female gametocytes predominates over the number of male, but this predominance may vary at different times between cloned infections (Cornelissen 1988, Schall 1989.…”

Plasmodium falciparum Gametocyte Formation In Vitro: Its Stimulation by Phorbol Diesters and by 8‐Bromo Cyclic Adenosine Monophosphateau WILLIAM TRAGER

“…Effects of PMA on gametocyte in petri dish cultures each holding 1.5 ml medium and 150 p1 of 50% red cell suspension with an initial parasitemia of 0.4%. Each dish was sampled on day 5 Table 2. EtOH-50,000 corresponded to the ethanol introduced with PMA at 20 ng/ml, and EtOH-20,000 to that introduced with PMA I, Means for the 3 dishes with standard deviation.…”

“…falciparum this was shown when the 1 st microscopically isolated clones of this species were grown up in culture and found to produce gametocytes of both sexes [29]. It follows that a single erythrocytic merozoite must contain in its haploid genome the information for both sexes of gametocytes as well as for the asexually reproducing forms [5]. Environmental signals must then determine the pathway of differentiation [9].…”