Sex is ubiquitous in nature, from simple viruses to complex multicellular organisms. However, we understand little about its origin(s), in particular the conditions and mechanisms that allowed sex to evolve and assume its current fundamental evolutionary role. In prokaryotes and lower eukaryotes, sex is facultative and is triggered by environmental stress, suggesting that sex might have evolved as a response to stress and its consequences, including the overproduction of DNA-damaging reactive oxygen species (ROS) generally associated with stress . To address this hypothesis, we tested the potential involvement of naturally-produced ROS in a sexual process, using the facultatively sexual multicellular green alga, Volvox carteri.
We reported that (i) sexual induction and development are drastically inhibited in the presence of antioxidants, and (ii) the sex response exhibits a dose response pattern similar to that known to characterize cellular responses to H2O2-induced DNA damage (Nedelcu and Michod 2003). This is the first report that shows an involvement of naturally-produced ROS, and likely ROS-induced DNA damage, in a sexual process and in a multicellular lineage. Our data extend the involvement of ROS into a new range of biological processes. These findings have important implications for the evolutionary origin and the adaptive significance of sex.
Recently, we have shown that (i) sex is induced by a two-fold increase in the level of cellular ROS (triggered by both the natural sex-inducing factor - heat stress, and by blocking the mitochondrial electron transport chain), and (ii) ROS activate sex genes, including the sexual inducer gene (Nedelcu, Marcu and Michod 2004).
We have also suggested a mechanistic and evolutionary connection between sex, cell-cycle arrest and apoptosis via ROS and DNA damage. We are currently investigating the connection between sex and apoptosis as alternative responses to distinct levels of stress, ROS and DNA damage in the multicellular green alga, Volvox carteri (Nedelcu and Michod 2003).
(A) Heat-induced (i.e.,
42.5oC for 120 minutes) sex response (solid squares) and cell-cycle
arrest of gonidia (solid circles) as a function of algal density; at high algal
densities (and likely increased ROS levels, associated with both the crowding
effect and the increased level of sexual inducer), cell-cycle arrest replaces
sex as a stress response. Percentage of arrested gonidia were
calculated as the percentage of females (relative to the total number of
females) in which more than half of the gonidia have not developed into embryos
by the second day after exposure to heat-shock. (B) Heat-induced (i.e.,
43.5oC for 120 minutes) apoptosis in gonidia as evidenced by the fast
(i.e., several hours) and complete dissolution of the gonidia; the slight
concavities that distort the usual spherical shape of the colony are due to
collapses of the somatic cell sheet at the sites where gonidia used to be;
somatic cells appear unaffected as they swim and provide the colony with
motility for another couple of days. (C) Heat-induced apoptosis and sex; gonidia
that do not undergo apoptosis develop into sexual embryos.
Figure 2. The localization of reactive oxygen species during heat-stress as evidenced with fluorescent microscopy and H2-DCFDA, a dye that becomes fluorescent when oxidized in the presence of cellular hydrogen peroxide.
To provide additional support for the suggestion that sex evolved as a response to oxidative stress, I addressed the hypothesis that genes involved in sexual induction are evolutionarily related to genes associated with various stress responses. The evolutionary history of genes specific to the sexual induction process in V. carteri – including those encoding the sexual inducer (SI) and several SI-induced extracellular matrix (ECM) proteins suggests an evolutionary connection between sex and stress at the gene level, via duplication and/or co-option (Nedelcu 2005).
As most types of stress result in the overproduction of ROS, we believe that our findings will prove to extend to other facultatively sexual lineages, which could be indicative of the ancestral role of sex as an adaptive response to stress and ROS-induced DNA damage.
Nedelcu AM and RE Michod. 2003. Sex as a response to oxidative stress: The effect of antioxidants on sexual induction in a facultatively sexual lineage. Proc. Royal Society London B: Biological Sciences 270: S136-S139.
Nedelcu, AM, O Marcu, and RE Michod. 2004. Sex as a response to oxidative stress: A two-fold increase in cellular reactive oxygen species activates sex genes. Proceedings of Royal Society London B: Biological Sciences 271: 1591-1596.
Nedelcu AM. 2005. Sex as a response to oxidative stress: Stress genes co-opted for sex. Proceedings of Royal Society London B: Biological Sciences 272: 1935-1940