Parasexuality of Candida Species

Abstract

While most fungi have the ability to reproduce sexually, multiple independent lineages have lost meiosis and developed parasexual cycles in its place. Emergence of parasexual cycles is particularly prominent in medically relevant fungi from the CUG paraphyletic group of Candida species. Since the discovery of parasex in C. albicans roughly two decades ago, it has served as the model for Candida species. Importantly, parasex in C. albicans retains hallmarks of meiosis including genetic recombination and chromosome segregation, making it a potential driver of genetic diversity. Furthermore, key meiotic genes play similar roles in C. albicans parasex and highlights parallels between these processes. Yet, the evolutionary role of parasex in Candida adaptation and the extent of resulting genotypic and phenotypic diversity remain as key knowledge gaps in this facultative reproductive program. Here, we present our current understanding of parasex, the mechanisms governing its regulation, and its relevance to Candida biology.

Sex in protists: A new perspective on the reproduction mechanisms of trypanosomatids

“…Organisms can be classified as obligate sexual (i.e., reproduction occurs exclusively through meiosis), parasexual (i.e., non-meiotic recombination with ploidy reduction, found in some unicellular eukaryotes) ( Pontecorvo et al, 1953 ; Mishra et al, 2021 ), obligate asexual, or facultative sexual (i.e., sexual and asexual reproduction are present). Facultative sex is found in various organisms ( Dacks and Roger, 1999 ; Otto, 2009 ), from plants that reproduce by cross-pollination, self-pollination, and vegetative reproduction ( Holsinger, 2000 ) to invertebrates ( Suomalainen, 1962 ) that rely on both sexual reproduction and parthenogenesis, such as the Cape honey bee ( Apis mellifera capensis ).…”

“…Parasexual recombination events involving trypanosomatids have been reported in T. cruzi ( Gaunt et al, 2003 ; Schwabl et al, 2019 ) and in Leishmania ( Sterkers et al, 2014 ), through genetic exchanges by nuclear fusion with reduced ploidy without the involvement of meiotic processes, as in fungi ( Mishra et al, 2021 ). The parasexuality can be considered an alternative pathway to meiotic recombination, since during nuclear fusion recombination between parental genomes can also occur, increasing offspring diversity ( Forche et al, 2008 ).…”

Similarities and Differences among Species Closely Related to Candida albicans: C. tropicalis, C. dubliniensis, and C. auris

“…While most fungi reproduce sexually, C. albicans has been shown to have parasexual cycles in which, after the fusion of diploid cells, rather than meiosis, coordinated loss of chromosomes occurs, resulting in viable progeny; this pathway of reproduction increases genetic diversity and contributes to adaptation to stressful environments, but also may mediate drug resistance [103]. The evolutionary role of reproduction, especially parasexual, in other medically important species of the genus Candida has become the subject of recent studies that discuss in detail the regulation of its mechanisms and importance in the evolution of pathogenicity [104][105][106]. Although C. albicans, C. tropicalis, and C. dubliniensis, due to their close relationship, share common features of the parasexual cycle, such as mating between diploid cells, the presence of a stable tetraploid form, coordinated loss of chromosomes, and the ability of diploid progeny to reenter the parasexual process, they also developed their unique attributes of those processes [104,106].…”

“…The evolutionary role of reproduction, especially parasexual, in other medically important species of the genus Candida has become the subject of recent studies that discuss in detail the regulation of its mechanisms and importance in the evolution of pathogenicity [104][105][106]. Although C. albicans, C. tropicalis, and C. dubliniensis, due to their close relationship, share common features of the parasexual cycle, such as mating between diploid cells, the presence of a stable tetraploid form, coordinated loss of chromosomes, and the ability of diploid progeny to reenter the parasexual process, they also developed their unique attributes of those processes [104,106]. For example, in the case of C. tropicalis, the possibility of generating hexaploid progeny has been reported by mating homothallic and heterothallic tetraploid products with diploid cells and the possibility of pheromone-assisted a-a homothallic mating without the need to white-to-opaque switch [104,106].…”

“…Although C. albicans, C. tropicalis, and C. dubliniensis, due to their close relationship, share common features of the parasexual cycle, such as mating between diploid cells, the presence of a stable tetraploid form, coordinated loss of chromosomes, and the ability of diploid progeny to reenter the parasexual process, they also developed their unique attributes of those processes [104,106]. For example, in the case of C. tropicalis, the possibility of generating hexaploid progeny has been reported by mating homothallic and heterothallic tetraploid products with diploid cells and the possibility of pheromone-assisted a-a homothallic mating without the need to white-to-opaque switch [104,106]. In turn, C. dubliniensis, compared to C. albicans, shows a much higher white-to-opaque frequency and does not show clumping dependent on mating, which results in less efficient intraspecific mating than interspecies mating [104].…”