Jpn. J. Protozool. Vol. 43, No. 2. (2010)89

On the origin of sexual reproduction: a hypothesis
Yoshiomi TAKAGI
1-1 Kitada-cho, Kamitakano, Sakyo-ku, Kyoto 606-0036, JapanSUMMARY
Alternation of haploid and diploid is a common feature of the sexual reproduction. Before
establishment of such sexual haploidization through meiosis and sexual diploidization throughfertilization, I hypothesize the asexual cycle alternating asexual haploidization and asexual
diploidization, which deserves to be called primitive sexual reproduction.
Key words: Primitive sexual reproduction, Asexual haploidization, First eukaryote, Genomicenlargement, Safety measure

Essential characteristics of sexual reproduction
Hypotheses on the origin of sexual reproduction have been almost exclusively on the origin ofsex or on the advantage of sexuality (Hamilton etal., 1990; Maynard Smith and Szathmáry, 1999;
Zimmer, 2009). Here I propose a hypothesis on theorigin of sexual reproduction in a completely newcontext.
General features of sexual reproduction are:(1) sexual differentiation, (2) genetic diversification, (3) rejuvenation (initiation of new generation), (4) meiosis and fertilization, and (5) reconstruction of soma from germ.
I have long engaged in biology of aging andlifespan in the ciliate protozoan Paramecium(Takagi, 1988, 1999) and wondered why some
Tel/Fax: ＋81-75-791-6846
E-mail: takagi@cc.nara-wu.ac.jp
Received: 27 May 2010; Accepted: 15 July 2010.
This article is based on the study first reported in theauthor’s book entitled “On the lifespan (in Japanese:Jyumyo-ron), NHK Publishing, Inc., Tokyo, 2009.”

species of Paramecium undergo autogamy as ameans to alternate generations. Autogamy is a
specific form of sexual reproduction including theabove-mentioned (3)~(5), but lacks (1) and (2).
From the evolutionary viewpoint, autogamy may
not be regarded as sexual reproduction because of
the lack of (1) and (2), but from the viewpoint ofdevelopment, autogamy is regarded as sexual reproduction because it satisfies (3)~(5). In fact,
autogamy played a historical role of denying theassertion of immortality of P. aurelia by revealing
the overlooked autogamy, and contributed to establish the concept of clonal life cycle: it begins
with sexual reproduction and consists of immaturity, maturity and senescence terminating with clonal death (Sonneborn, 1954). Contrary to autogamy,
bacterial conjugation satisfies (1) and (2) but lacks(3)~(5). It is likely, therefore, that (3)~(5) rather
than (1) and (2) are the more fundamental featuresof the genuine sexual reproduction.
Although the features mentioned above arecharacteristic to the sexual reproduction, (5) isseen also during the asexual reproduction: for ex-90

Origin of sexual reproduction

ample, both soma and germ are formed in an asexual aggregate of Dictyostelium and in colonial phytomonads such as Eudorina, Pandorina and Volvox; the somatic macronucleus is rebuilt from thegerminal micronucleus at every cell division in
Loxodes (Grell, 1973). If fertilization and meiosis
are viewed respectively as diploidization (n→2n)
and haploidization (2n→n), it is no less a process
than the asexual reproduction of a haploid cell.
The idea that the process of sexual and asexual
reproductions is not necessarily discriminatedstrictly but somehow related to each other led me
to postulate that the primitive form of sexual reproduction might have emerged directly fromasexual reproduction.
As shown in Fig. 1, the asexual reproductionof a haploid cell consists of duplication (n→2n)
and distribution (2n→n) of the genome, and thesimplest form of sexual reproduction comprising
one-step meiosis consists of cell fusion(fertilization) (n→2n) and segregation (meiosis)(2n→n). Although n→2n and 2n→n in Fig. 1 arediploidization and haploidization, respectively, butthey are only temporary, not real diploidizationand haploidization.
In Fig. 2, asexually reproducing cycles consisting of genomic duplication and distribution are
shown as du and di for the haploid cell, and Du
and Di for the diploid cell. Real diploidization(n→2n) takes place if duplication doubled in the
haploid cycle (du-Du), and real haploidization(2n→n) takes place if distribution doubled in the
diploid cycle (Di-di). To distinguish the diploidization through the du-Du pathway from the sexual
diploidization through fertilization, I here call it
asexual diploidization. Similarly, to distinguish thehaploidization through the Di-di pathway from thesexual haploidization through meiosis, I here call it
asexual haploidization.
How the first eukaryote emerged from the prokaryote?
It still remains unknown how the first eukar-Fig. 1. Diploidization and haploidization are common inboth asexual and sexual reproductions. Asexual reproduction of a haploid cell consists of genomic duplication anddistribution, and sexual reproduction of a one-step meiosis
consists of cell fusion and segregation. Modified fromTakagi (2009).

Fig. 2. Diploidization and haploidization in asexual reproductions. Diploidization occurs if duplication is doubled(du-Du) in the haploid cycle, and haploidization occurs if
distribution is doubled (Di-di) in the diploid cycle. Modified from Takagi (2009).

yote emerged. Any hypotheses including endosymbiosis cannot answer this question, because
they premise the existence of the eukaryote: endocytosis depending on the ability of the host to incorporate the symbiont needs cytoskeletons that
only the eukaryote possesses. Even the excellent
hydrogen hypothesis (Martin and Müller, 1998) is
not exceptional: it explains the origin of the eukaryotic metabolic system, not the origin of the eukaryote itself.
Genomic and cellular enlargement are supposed to be the primary incidence giving the way

Jpn. J. Protozool. Vol. 43, No. 2. (2010)

to the first eukaryote. Genomic enlargement
through whole-genome or partial-genome duplications and horizontal transfers makes many newtasks possible by introducing new proteins. Cellular enlargement occurs concomitantly with thegenomic enlargement (Alberts et al., 2002; Storchová et al., 2006), although the mechanism toscale the size is poorly understood. A tenfold increase in cell diameter from 1 to 10 microns on
average results in hundredfold increase in cell surface area and thousandfold increase in cell volume.
Among the newly introduced proteins, actins andtubulins seem to be earliest because their genetic
rudiments are found in prokaryotes as ftsA andftsZ, respectively (Pilhofer et al., 2007), and areespecially important because they can function as
the cytoskeleton. It supports the enlarged cellstructure. It makes endocytosis possible. It contributes to establish the internal membrane system,
which is useful for compensating the lack of thecell surface, for transporting proteins in an enlarged cell, and for constructing the nuclear membrane to store the enlarged genome safely.
However, the enlarged genome causes a newproblem, because it requires elongated time for its
duplication. Elongated time for duplication increases the opportunity of harmful mutations.
Safety measures for enlarged genome are needed. I
propose two safety measures. One is the differentiation of germ and soma, and the other is the asexual diploidization of the genome (n→2n).
Evolution of sexual reproduction
The du-di module of the asexual reproduction cycle of a haploid cell is capable of repeatinginfinitely if the genome size is small like bacteria,
because the division rate is rapid enough to overcome a harmful mutation; more than a million
cells would be produced for 7 hours if a cell divided exponentially every 20 minutes (221>106).
The haploid eukaryotic cells with enlarged
genome have to undergo asexual diploidization
through the Di-di pathway to avoid fatal muta-91

tions; the loss of function of a gene by mutation
can be masked by the complementary gene. However, the Du-Di module of the diploid cell division
could not repeat indefinitely, because the functionof the diploidy to mask the harmful recessive mutations would someday become not to work anymore. Since all of the haploidal genes could beexpressed, haploidization would result in extinction if it occurred too late, or would result in rejuvenation (restoration to the original state) if it occurred before the accumulation of mutations became serious. The timing of the asexual haploidization through the Di-di pathway would play a roleof inspecting the usefulness of the accumulated
mutations. A new genotype could emerge if somemutations, each being hazardous, were beneficial
when worked together. Thus the periodical repeatsof the asexual diploidization and the asexual haploidization resemble the sexual reproduction inthat they cause rejuvenation and genetic variation
to some extent. I name this process “primitive sexual reproduction” (Fig. 3).
The other reasoning to insist that the cycle of
the asexual diploidization and the asexual haploidization is suitable to be called “primitive sexual reproduction” is that this cycle can accept thediploidization achieved by cell fusion. This may be
the original form of sexual reproduction-I including sexual differentiation and one-step meiosis

Fig. 3. Primitive sexual reproduction composing alternation of asexual cycles between haploidy and diploidy.
Asexual diploidization through the du-Du pathway is asafety measure. Asexual haploidization through the Di-dipathway is a means to inspect the usefulness of accumulated mutations, resulting in rejuvenation and genetic variation to some extent. Modified from Takagi (2009).

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Origin of sexual reproduction

Fig. 4. The asexual alternation cycle between haploid anddiploid can accept the sexual diploidization through cellfusion so that the sexual reproduction-I including one stepmeiosis is established. Modified from Takagi (2009).

Fig. 5. The primitive sexual reproduction missing the haploid cycle contributes to establish the sexual reproductionII comprising haploidization through two-step meiosis anddiploidization through fertilization. Modified from Takagi(2009).

accompanying recombination (Fig. 4). Also, theprimitive sexual reproduction missing the haploidcycle can accept the sexual reproduction-II consisting of diploidization through fertilization andhaploidization through two-step meiosis (Fig. 5).
The timing of meiosis appears to have been programmed as the timing of sexual maturation.
Because pairing of the homologous chromosomes is involved in meiosis and it facilitates recombinational DNA repair, any form of sexual
reproduction including meiosis and fertilization
may be advantageous. This appears to be the reason why autogamy has survived without benefitsof genetic variation through sexuality.

Consequently the sequence of evolution of
the sexual reproduction can be viewed as follows.
The asexual reproduction of early eukaryotes thatevolved the enlarged genome/cell size cannot beimmortal; they become diploid to avoid harmful
mutations and periodically become haploid to
avoid senescence due to accumulated mutations.
The asexual alternation cycle between haploid anddiploid resulting from the Di-di and du-Du pathways has the advantage of yielding rejuvenationand genetic variation by checking the usefulness ofaccumulated mutations. The cycle of the asexual
diploidization and the asexual haploidization is,therefore, worth calling primitive sexual reproduction although no sexuality is involved. When sexual differentiation, gametic fusion and recombination become available, the sexual reproduction-I
that contains one-step meiosis, and then the sexualreproduction-II that contains two-step meiosis
have been connected to the preexisting cycle of theprimitive sexual reproduction.
Test for Validity of the hypothesis
Evolution of the ploidy-based life cycle isdirected from the exclusive haploidy to the diploidy dominancy via the alternation of haploidy anddiploidy (Fig. 6). The alternation of haploidy anddiploidy observed in ferns, mosses, brown alga etc.
is deemed to be driven by diploidization throughfertilization and haploidization through meiosis.
However, the hypothesis of the primitive sexual
reproduction predicts an alternative cycle of theasexual diploidization through the du-Du pathway(n→2n) and asexual haploidization through the Didi pathway (2n→n) in these organisms. This isworth examining.
It is a puzzling question why some unicellular eukaryotes such as Amoeba and Euglena can
asexually grow infinitely. Cells with infinite capacity to divide are exemplified in daughter cellsof budding yeasts (Liu et al., 2010), embryonicstem cells, cancer cells and so on. But the possibility that Amoeba and Euglena are undergoing theJpn. J. Protozool. Vol. 43, No. 2. (2010)93

Fig. 6. The ploidy-based life cycles are usually divided into three groups; 1) exclusively n, 2) alternation of n and 2n, and3) 2n dominancy. Although the alternation of n and 2n is believed to be caused by fertilization and meiosis, I hypothesize
the alternation of asexual diploidization (n→2n) and asexual haploidization (2n→n) according to the manner shown inFig. 2. Dotted lines indicate the possible alternative to be examined. Modified from Takagi (2009).

primitive sexual reproduction with the cycle ofasexual diploidization and asexual haploidization
appears plausible and amenable to experimental
test.
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