Are eukaryotic microorganisms clonal or sexual? A population genetics vantage.

Abstract

We argue that the mode of reproduction of microorganisms in nature can only be decided by population genetic information. The evidence available indicates that many parasitic protozoa and unicellular fungi have clonal rather than sexual population structures, which has major consequences for medical research and practice. Plasmodium falciparum, the agent of malaria, is a special case: the scarce evidence available is contradictory, some suggesting that uniparental lineages may exist in nature. This is puzzling (because P. falciparum is known to have a sexual stage) and poses a challenge that can be readily settled by ascertaining the frequency distribution of genotypes in natural populations.Sexual reproduction is generally assumed to be a common mode of reproduction of eukaryotes. In the case of parasitic protozoa, the assumption of sexual reproduction relies largely on the presumption that these organisms are diploid, as well as on the occurrence of sexual recombination in the laboratory under appropriate circumstances (review in ref. 1), rather than on relevant evidence obtained from nature. Yet, whether or not sexual reproduction prevails in these organisms is of considerable medical and agronomic consequence as well as of scientific interest. These eukaryotic microorganisms include the agents of malaria, sleeping sickness, Chagas disease, and other parasitic diseases that affect more than 10% of the world population. The strategies for developing vaccines or curative drugs as well as for diagnosis and treatment are different for clonal and for sexual organisms.That sexual reproduction may occur in laboratory cultures or even occasionally in nature does not by itself settle the issue, since that simply manifests that the potentiality for sexual reproduction has not been lost. What remains to be determined is the prevailing mode of reproduction of these organisms in natural circumstances. The evidence to settle the matter exists for some of these organisms and could be obtained for others without massive investment of resources or new scientific or medical advances. We herein advance a sustained argument to show that population genetic evidence and population genetic theory is all that is needed to ascertain the extent to which, if at all, these (or any other) organisms reproduce sexually in nature. We have already reviewed the evidence for Trypanosoma cruzi, the agent of Chagas disease (2), and some other protozoa (3). Here we develop further the argument and present the results of a survey of the available evidence for parasitic protozoa and unicellular fungi. CLONALITY IN MICROBIAL EUKARIOTESThe two genetic consequences of sexual reproduction are segregation and recombination. Population genetic methods make it possible to ascertain whether or not the distribution of genotypes in natural populations is consistent with the occurrence of segregation and recombination. The kind of evidence that is needed is the frequency distribution ofgenotypes rather than the direct observation of sexual or clonal r...

Toxoplasma gondii, “new” genotypes and virulence

“…The practical implication of a clonal population structure is that biological characteristics can be attributed to a genetically well defined subset of the parasitic population (Tibayrenc et al, 1991). That is the case for mouse-virulence of the three main types of Toxoplasma.…”

“…Several reports also suggest a higher pathogenicity in humans and an association with ocular toxoplasmosis or severe cases of acquired toxoplasmosis in immunocompetent patients. T he three main types respond to the criteria for a clonal population structure of Toxoplasma (isolation of identical multilocus genotypes over large geographic areas and at interval of several years, and a strong linkage disequilibrium) (Tibayrenc et al, 1991). This simple clonal structure is accompanied by a low genetic divergence between the three main lineages (only ≈ 2 % divergence at the DNA sequence level between lineages).…”

First characterization of Candida albicans by random amplified polymorphic DNA method in Nicaragua and comparison of the diagnosis methods for vaginal candidiasis in Nicaraguan women

“…The f test is based on Montecarlo simulations with 10 4 iterations. A level of significance < 10 -4 means that no case was observed out of 10 4 iterations (Tibayrenc et al 1991).…”

“…Early studies addressing this question (Tibayrenc et al 1991, Caugant & Sandven 1993) have recorded low levels of linkage disequilibrium (nonrandom association of genotypes occuring at different loci), by comparison with other pathogens such as Trypanosoma or Leishmania (Tibayrenc et al 1990). By constrast, other authors (Hellstein et al 1993, Pujol et al 1993, Xu et al 1999, Arnavielhe et al 2000 have found considerable levels of linkage in differents C. albicans populations and have concluded that these populations propagate clonally.…”

The molecular epidemiology of parasite infections: Tools and applications

“…A clonal population structure does not imply that genetic exchange is absent in the species, only that it is too rare to erode the basic genetic patterns of clonality. Using these criteria, Tibayrenc et al [53,56] identified a number of species of parasitic protozoa, including Entamboeba histolytica, Giardia duodenalis, Lieshmania tropica, L. major, Trypanosoma brucei, T. cruzi and T. vivax, as having an essentially clonal population structure. Subsequent studies have shown that the situation is rather more complex and different populations of the same species often show different degrees of clonality [57].…”