Genetic conflicts and intercellular heterogeneity.

Adaptation is what elevates biology above mere chemistry and physics, and the salient feature of adaptation is that it is generally associated with individual organisms. The edge of an organism is a crucial boundary, within which we generally find adaptive cooperation and outside of which we find competition and conflict. Therefore, for understanding adaptation, it is important to have a clear conception of the forces that created and maintain the individual organism and to understand when organisms occur in forms that challenge the identity of the individual as an adapted unit. For multicellular organisms, genetic homogeneity is thought to be the most essential element; each cell will be selected to act for the good of the whole if the other cells are genetically identical. Therefore, multicellular individuals that break this rule present a challenge to our conception of the organism. As a preliminary, we would like to clarify the subject of this discussion. The cases of intraorganismal genetic heterogenity discussed by Pineda-Krch & Lehtila (2004) would be better described as intercellular heterogeneity – different cells of the same individual having different genes. Heterogeneity can also lead to conflicts between genes within the same cells, including meiotic drive, transposition, genomic imprinting, and conflict arising because of atypical transmission of B chromosomes or sex chromosomes. These are also interesting, and for some of the same reasons, but here our focus is on the narrower phenomenon of differences between cells of the same organism. When does intercellular heterogeneity challenge the identity of an individual as an adapted unit? This may depend on the type of heterogeneity. A mosaic arises when there is a mutation in a part of an individual that does not affect the entire individual. It can be in either somatic or germ-line tissues. A chimera is an organism that forms when two genetically separate and different individuals merge. These three forms of intraindividual heterogeneity do not equally challenge our view of what an individual is. Somatic mutations must arise in all multicellular organisms and any individual with a large number of cells and a large number of mutable genes is going to be a somatic mosaic to some degree. Such mutations can be fatal to the individual, as is often the case with cancer, but they are not fatal to our concept of the individual. Such mutations are not inherited. A germ-line mosaic is potentially a greater problem because the variant can compete for access to the next generation. But the competition is usually limited by passage through a single-cell bottleneck (Maynard Smith, 1989). This means that each mutation, however effective a cheater, gets only one opportunity to cheat. This keeps it from being too much of a threat to individuality. Chimeras are more challenging because within-individual variation does not go away, but is recreated each generation although mergers. A single exploitative mutation can therefore spread through the entire population, which is impossible in mosaics. This complicates our view of the individual as an adapted unit because selection will operate on the chimeric individual, but may also favour exploitation by one of the chimeric partners. This in turn can favour genes that resist fusion, or resist exploitation after fusion. Rarity of chimeras is expected as it involves cooperation among unrelated lines. If chimerism is much more common than is generally believed, then it could challenge our view of the importance of clonality in maintaining the individual as an adapted, selected whole. The small number of references given in Pineda-Krch and Lehtila do not yet make a strong case for high levels of chimerism. On the other hand, there are several strong arguments that clonality and absence of conflict are not essential to organismal function. First, there are a few examples of chimeras where conflict has been demonstrated, but it does not destroy organismal function. Chimerism among unrelated individuals occurs in the social amoeba Dictyostelium discoideum, when individual, predatory amoebae starve. They follow cAMP gradients, forming a slug with up to hundreds of thousands of cells that may be made up of several genetically distinct clones. The slug moves up through the soil and leaf litter, towards light and away from ammonia, then forms a fruiting body consisting of 20% dead stalk cells that support the remaining cells differentiated as spores (Kessin, 2001). The stalk provides a dispersal advantage to the remaining cells at the ultimate cost to themselves. These fruiting bodies may be clonal or chimeric. Even cells in chimeric fruiting bodies have thousands of clone mates present, making overall relatedness high, averaging about 0.5 in small soil samples that might be the arena over which cells aggregate (Fortunato et al., 2003). There is conflict over contribution to stalk cells in chimeras, with some clones successfully contributing proportionally more to spore than to stalk (Strassmann et al., 2000). Another cost of chimerism is that chimeric slugs move less far than slugs of pure clones of the same size, perhaps because of competition within the slug (Foster et al., 2002). However, the study also points to the Correspondence: Joan E. Strassmann, Department of Ecology and Evolutionary Biology, Rice University, Houston, TX, USA. E-mail: strassm@rice.edu