Abstract

Evolution of independently breeding species into males and females (gametes) hasremained a puzzle. Given the significant advantages of sexual reproduction overasexual reproduction as a long-term species survival strategy; here, we pose thequestion whether there is some form of meiosis inAcanthamoebaspecies, which represents our ancient lineage. The recently availableAcanthamoeba genome revealed several genes implicated in meiosisin sexual eukaryotes such asSpo11,Mre11,Rad50,Rad51,Rad52,Mnd1,Dmc1,Msh, andMlh, suggesting thatAcanthamoeba is capable ofsome form of meiosis, inferring the presence of sexual reproduction inAcanthamoeba, and that meiosis evolved early in eukaryoticevolution.

Sexual Reproduction (Meiosis) in AsexualAcanthamoeba?

Evolutionary biology studies have shown that amoebae evolved into intermediateorganisms, which then evolved into higher organisms such as fish, reptiles, amphibians,birds, mammals, and finally humans. Despite notable similarities in the molecular andcellular architecture of various cell types of eukaryotic lineage, the origin of maleand female sexes has remained unclear. Among lower eukaryotes such asAcanthamoeba, the mode of reproduction is generally considered to beasexual, i.e., mother cell divides into two daughter cells via binary fission or insimple terms, amoebae do not need any genetic material from another organism toreproduce. In this context,Acanthamoeba are ‘God's favoriteholy creation’ as they can reproduce without needing a partner of the samespecies. There is only one amoeba and all others are clones. This is a remarkableproperty to increase the progeny of a particular species, without the need of a‘male’ counterpart. It simplifies the life cycle of the species and ensuresspecies survival under solitary conditions without the fear of species termination. Howand when independently breeding species evolved into males and females (gametes) hasbeen puzzling evolutionary biologists for centuries. Giving up reproductive autonomy andselecting the evolutionary path of acquiring greater genetic diversity, where both malesand females are required, together with far more ATP-dependency in order to ensure theprocreation to further the existence of a particular species is a difficult path, yet itis widespread. Given the significant advantages of sexual reproduction over asexualreproduction, can there be male and female amoeba? In support, the evolutionary theorysuggests that the species, which reproduce by cloning (do not mix genetic material) donot cope well with varied environments or may not survive when exposed to noxiousagents¹ and this is a short-lived strategy,while sexual reproduction (exchange of genetic material) allows them to evolve quicklyand develop new characteristics to adapt to changing environments. AsAcanthamoeba represents an ancient lineage (over a billion yearsold),² which has survived catastrophic events,thus it must have developed mechanisms to endure harsh conditions. Here, we pose thequestion whether there is some form of meiosis, i.e., exchange of genetic materialresulting in genetic variation inAcanthamoeba.

Evidence of Meiotic Genes inAcanthamoeba

The significant event of sexual reproduction in eukaryotes is generation of gametes(haploid cells), a processes known as meiosis, followed by fusion of gametes or nucleito bring about new combinations of genetic material. Thus, the presence of meiosis canbe considered as a hallmark of sexual reproduction in eukaryotes. There is no evidenceof meiotic division cycle or genetic recombination inAcanthamoeba.However, using the recently available genome information,³ we identified several genes implicated in meiosis such asSpo11,Mre11,Rad50,Rad51,Rad52,Mnd1,Dmc1,Msh, andMlh (Table 1), which are widely present amongsexual eukaryotes. The selection of meiotic genes was based on the fact that they havemajor meiotic functions in animals, fungi and plants and some protists.⁴ These data indicate thatAcanthamoeba genome encodes homologous of key genes required formeiosis. Among animals, fungi, and plants, these genes are largely known for meiosis.Among meiotic genes,Acanthamoeba does not appear to have homologous ofHop orPms genes;⁵ however, it is not clear whether this is because of the absence of thesegenes inAcanthamoeba genome or whether they were lost duringevolution. Regardless, the presence of several genes that are involved in meiosissuggests the presence of meiosis inAcanthamoeba. The ability ofAcanthamoeba to undergo meiosis warrants further experimentalinvestigations for the identification of meiosis signature proteins and these are underinvestigation. The available genomic data³(http://eupathdb.org/eupathdb/) support the presence of meiotic genes inAcanthamoeba. Given that the surveyed genes are known for meiosis inanimals, fungi and plants, their role in non-meiotic function inAcanthamoeba is unlikely. Based on the presence of these meioticgenes, it is reasonable to hypothesise thatAcanthamoeba is capable ofsome form of meiosis. Additionally, these findings suggest that meiosis evolved early ineukaryotic evolution. This is not an entirely surprising finding as sexual reproductionis quite common even among prokaryotes (e.g., via sex pili) as well as lower eukaryotessuch as ciliates and complex sexual systems have been described for various ciliatespecies. Among many lower eukaryotes, sexual and asexual reproduction processes coexistwithin the same species.⁶ In addition toPlasmodium and Kinetoplastids, the presence of meiotic genes inEntamoeba,Encephalitozoon,Giardia,Naegleria,^5–10 and nowAcanthamoeba suggest the presence of meiosis across variouseukaryotic domains and the likely presence of ‘sexual cycles’ in thesespecies. Notably, the meiosis signature genes inAcanthamoeba describedhere are assigned functions based on sequence information, and further identification ofmeiosis genes based on orthologous relationships with known meiotic organisms, ratherthan sequence homology, and their experimental investigation will provide a completeunderstanding of meiosis, inferring the presence of ‘sexual reproduction’ inthis fascinating organism. Also, it is worth noting that meiosis signature proteins havebeen found in species with no meiotic pathway, such asCandidaalbicans, thus experimental studies at the functional level are needed toaddress this issue. If some form of meiosis is proven inAcanthamoeba,the next questions will be identification of molecular mechanisms of ‘sexualreproduction’ including secretion of ‘pheromones’ (mating signals),their receptors leading to morphogenetic changes in the participating cells. Being oneof the most early diverging eukaryotes,Acanthamoeba represents animportant species to provide a phylogenetic key to understanding the origin andevolution of meiosis. This coupled with the recently available genome sequenceinformation together with high throughput genomics technology, axenic cultivation, andinnovative approaches to make these parasites genetically tractable means thatAcanthamoeba is an attractive model to scientists for phylogenomicstudies.

In summary, the presence of meiotic genes suggests that (i)Acanthamoeba may be capable of meiosis, inferring the presence ofsexual reproduction, (ii) meiosis evolved early in eukaryotic evolution, or (iii) theyare adaptational strategies which were developed in recent millenniums and/ortransformational to a higher level of survival. Further experimental investigations willidentify the conserved meiotic machinery of these genes that encode a variety ofcomponent proteins, including those involved in meiotic recombination. Being one of themost early diverging eukaryotes,Acanthamoeba represents an importantspecies to provide a phylogenetic key to understanding the origin and evolution ofmeiosis.

Key findings

• Several meiotic genes were identified inAcanthamoeba genome,which are widely present among sexual eukaryotes.

• Acanthamoeba is capable of meiosis, inferring the presence ofsexual reproduction.

• AsAcanthamoeba represents our ancient lineage, meiosisevolved early in eukaryotic evolution.

Acknowledgements

We are grateful for the kind support provided by the Aga Khan University.

Author Contributions

Both authors contributed equally to this manuscript and both read and approved its finalversion.

Disclaimer Statements

Contributors NAK mined the literature. RS examined genomes of differentorganisms. NAK and RS wrote the manuscript. Both authors read and approved the finalmanuscript.

Funding Funding was provided by Aga Khan University.

Conflict of interest The authors have no conflicts of interest.

Ethics approval Not applicable.

References