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A growing number of empirical and theoretical studies suggest that naturally occurring intraorganismal genetic heterogeneity (IGH) may be more common than previously believed (for review see Pineda-Krch & Lehtilä, 2004). That the occurrence of genetically heterogeneous organisms in nature is of deep biological significance was recognized by Williams (1966) in his seminal Adaptation and Natural Selection. Nevertheless, the matter has received little attention in ecological and evolutionary research, and issues such as the frequency, the mechanisms and the potential significance of IGH remain largely unexplored.

There seem to be two reasons for this omission and the general lines of argument can be summarized as follows: (i) it is important to maintain genetic homogeneity of an organism in order to avoid intraorganismal conflicts, hence IGH will be rare because there is strong selection against it and (ii) genetically heterogeneous organisms do not qualify as true gene vehicles and do not adhere to the predominantly accepted definition of individuality. Although the potential for IGH is acknowledged its significance is dismissed either because of its assumed rarity or the perceived difficulties in accommodating the idea within contemporary biological concepts. This line of reasoning is at least partially justified. That IGHs will often entail costs at the organism level is probably true, but currently we know little about the true distribution of effect, and as several of the commentaries show there is more to the story than what the statement suggests (Rinkevich, 2004; Santelices, 2004; Strassmann & Queller, 2004). It is also true that it would be difficult to accommodate IGH into the contemporary concept of individuality as, ever since Weismann, individuality has implied genetic homogeneity (Santelices, 1999). While several of the commentaries discuss the need for a revised individuality concept to accommodate situations such as IGH, Hutchings & Booth (2004) also appropriately point out that it is unlikely that any given definition will ever be applicable to all types of organisms. Indeed, the complexity of defining the individuality concept has been addressed on several occasions (Tuomi & Vuorisalo, 1989; Santelices, 1999). Nevertheless, a widely accepted conceptual revision has not yet occurred. Incorporating IGH into a revised concept of individuality will pose interesting challenges to theoretical and empirical research alike.

How common is genetic homogeneity?

  1. Top of page
  2. How common is genetic homogeneity?
  3. The usefulness of the concept
  4. Coexistence and extinction of lineages
  5. Acknowledgments
  6. References

Because coexistence of multiple genetic lineages within an individual is usually assumed to give rise to conflicts having detrimental effects to the organism, various means to ensure that genetic homogeneity is maintained have evolved. Developmental mechanisms such as the single-celled ontogenetic bottleneck that the zygote constitutes, apoptosis (Fagerström et al., 1998) policing-mediated control systems (e.g. the immune system) and histocompatibility systems [e.g. Rinkevich's (2004) fusibility alleles] ensure that the organism maintains its genetic integrity either by limiting the opportunities for IGH to arise or efficiently eliminating novel genetic lineages (Santelices, 2004). It is not clear, however, that any of these mechanisms evolved specifically in order to limit IGH. Several of the commentaries raise the issue of the limited number of studies identifying naturally occurring IGHs arguing that there is currently too little evidence to make a compelling case in favour of IGH as a common biological phenomenon (Hutchings & Booth, 2004; Strassmann & Queller, 2004). Unfortunately, the general attitude seems to be that the lack of studies only confirms that IGH is rare and hence cannot have much ecological or evolutionary importance and, consequently, this perpetuates the lack of study. The dearth of studies documenting IGH is of course not indicative of its true occurrence. The problem is not so much that there are few studies documenting IGH but rather that there are few studies specifically looking for it. It is compelling that the few studies that have attempted to identify and study naturally occurring IGH have had little trouble in finding it.

Rather than assuming that genetic heterogeneity must be rare and homogeneity is the rule, a more fruitful approach in ecology and evolutionary biology might be to ask under what conditions we would expect genetic homogeneity. Most studies have used organisms where IGH might be expected to be more common, e.g. clonal and modular organisms. We might expect that organisms such as Drosophila, mice and humans, that are sexually reproducing, short lived (relative to many modular and clonal organisms) and with few cell divisions between subsequent single-celled zygotic bottlenecks, have low levels of IGH. In reality, however, it is well established in the medical literature that human genetic heterogeneity such as mosaicism due to somatic mutations and foetal–maternal chimerism is common (see review for examples), or as Rinkevich (2004) puts it ‘…probably most adult women remain in a chimeric state decades after pregnancy…’. Clearly, the only reason we know this is because Homo sapiens is the most extensively studied organism that has ever existed. It is not only in medicine that the occurrence of IGH is well documented but also in fields such as mycology, phycology, horticulture and animal breeding (see Table of the review). While reviewing the literature in these fields will provide more insight into the ubiquity of IGH, ultimately studies with an ecological and evolutionary approach are needed to fully elucidate the mechanisms and consequences of IGH. Although speculative in the absence of supportive data, predictions such as those in the commentary by Rinkevich (2004) on the relative frequency and most likely phenotypic manifestations of the various types of IGHs can provide valuable insight that can aid in devising the empirical methodologies necessary in order to address these questions.

The usefulness of the concept

  1. Top of page
  2. How common is genetic homogeneity?
  3. The usefulness of the concept
  4. Coexistence and extinction of lineages
  5. Acknowledgments
  6. References

A highly inclusive concept will by definition omit specific details in favour of a classification based on one or several features that are in common. We agree with Pannell & Eppley (2004) that the IGH concept, barring further specifications, does not provide much evolutionary insight. It cannot, because the details that are being omitted are those that are important from an evolutionary perspective, e.g. the causal origin of the heterogeneity. All of the commentaries agree to various degrees that there is a fundamental distinction between organisms that are genetically uniform and organisms that are genetically heterogeneous. It is this distinction that IGH embraces. Future ecological and evolutionary studies addressing the various forms of IGH will have to approach different types of heterogeneities in different ways (Santelices, 2004).

Coexistence and extinction of lineages

  1. Top of page
  2. How common is genetic homogeneity?
  3. The usefulness of the concept
  4. Coexistence and extinction of lineages
  5. Acknowledgments
  6. References

The existence of IGH depends on the balance of processes that generate distinct lineages within an organism vs. the processes that eliminate individual lineages. The nature of these processes, e.g. their rates, mechanisms and magnitude of effect, is central in determining how prevalent genetically homogeneous and heterogeneous organisms will be and in which direction the balance tends to lean. While the potential costs and benefits of IGH are rarely addressed the processes involved in generating and eliminating IGH have received a fair amount of theoretical attention (Antolin & Strobeck, 1985; Klekowski, 1988; Otto & Orive, 1995; Otto & Hastings, 1998; Orive, 2001; Pineda-Krch & Lehtilä, 2002). These studies show that the opportunities for a mutant lineage to spread within an organism are very limited, but the large number of cell divisions in large and long-lived organisms works in favour of creating a genetically heterogeneous soma. It should be noted, however, that these theoretical models have specifically addressed the case of the dynamics of genetic mosaics. To our knowledge there are no theoretical studies addressing the formation and dynamics of chimeras. It would be interesting to theoretically address Rinkevich's (2004) concept of a window in ontogeny for chimera formation in a similar manner that previous theoretical work has addressed the dynamics of mosaic entities.

If IGH is able to persist within an organism, an important question that arises is how the genetically heterogeneous entity can replicate itself rather than its subunits independently. A necessary condition in order for the IGH to be inherited is that the sequestration of next generation's precursor cells has to be multi-celled, i.e. propagation has to be clonal. Even if clonal propagation takes place there is, however, no guarantee that the IGH will be maintained (Figure 1 in the review). Although the general processes driving the transitions between the homogeneous and heterogeneous states can be illustrated as in Figure 1 of the review, the details will clearly be specific for each particular system.

Notwithstanding the importance of the processes of persistence and disappearance of IGH, the focus of our review is primarily on the potential biological ramifications of the genetically heterogeneous state itself, i.e. the costs and benefits of the heterogeneity. While it seems intuitive that IGH most often will confer costs to the organisms and rarely benefits (Hutchings & Booth, 2004; Tuomi, 2004), estimating the actual distribution of effects is difficult without more empirical data. Nevertheless, it is possible, and also appropriate, to evaluate the type of effects that can be expected, which is one of the aims of our review. While we agree with Hutchings & Booth (2004) that in order to accept a hypothesis supportive data have to be available, we are not proposing an acceptance of the adaptive significance of IGH, which would indeed be premature. Rather we are proposing that there is compelling empirical and theoretical evidence that naturally occurring IGH sensu lato (i.e. not necessarily beneficial or adaptive IGH) is likely to be much more common that previously thought and consequently should be taken seriously as a biological phenomenon. Clearly we cannot say much about the frequency of beneficial IGH other than that it is a possibility that should be included in a full discussion of the potential costs and benefits of IGH. The specific mechanism and the circumstance under which an IGH arises will have a central role in determining the potential effects (Santelices, 2004). For example, the timing of the formation may fundamentally change the outcome of the heterogeneity (i.e. Rinkevich's a window in ontogeny concept). Strassmann & Queller (2004) point out that if chimerism is a common form of IGH then our assumption of the importance of maintaining genetic homogeneity in order to ensure the well-being and harmony of an organism would be seriously challenged. Interestingly evidence suggests that IGH may be more common than previously thought and that genetic homogeneity may not always be critical to organism function after all.

While current progress in our understanding of the role of IGH may seem to be hampered by the paucity of data from natural populations we believe that the real impediment is a conceptual resistance towards accepting that biological reality is seldom as straightforward as one would wish. It is curious that although the evidence for naturally occurring IGH is limited and in some cases circumstantial at best, the hallmark of individuality, the long-held assumption of genetic homogeneity, has even less supporting evidence. In other words, genetic homogeneity has rarely been shown, it has simply been a tacit assumption that conveniently fits our preconceived conceptual framework. As long as there is a lack of studies on the prevalence and significance of genetically heterogeneous soma the concept of IGH necessarily remains speculative – but so does the rejection of it.

Acknowledgments

  1. Top of page
  2. How common is genetic homogeneity?
  3. The usefulness of the concept
  4. Coexistence and extinction of lineages
  5. Acknowledgments
  6. References

We are grateful to all of the authors contributing the commentaries for their insights and comments that forced us to think long and hard about many of the issues ultimately improving and extending the scope of our review. We thank Sally Otto for commenting on a draft of the reply.

References

  1. Top of page
  2. How common is genetic homogeneity?
  3. The usefulness of the concept
  4. Coexistence and extinction of lineages
  5. Acknowledgments
  6. References