Traditionally, the genome has been viewed as a collection of DNA molecules that vary in composition between individuals and species, and variations that generate phenotypic differences have been assumed to occur in a more or less random manner. More recently, this view has been challenged by evidence that genomes are in fact reservoirs of adaptive phenotypic plasticity. This adaptive genome concept, where mutations that convey adaptive benefits are likely to occur at greater than random frequencies (Caporale 1999, 2000, 2003) represents a synthesis of ideas and evidence from several subfields and has its genesis in work by pioneers such as Dhobzhansky (1937), Dawkins (1976), McClintock (1984) and Trifinov (1989).
Prior to the rise of the adaptive genome concept most, if not all, non-coding DNA was believed to have no biological function. This view was a response to the observation that genome size shows no significant relationship with organismal complexity: The so-called c-value paradox (Zuckerkandl 1976; Capy 2000; Petrov 2001). The suggestion that tracts of non-protein-coding repetitive DNA play a key role in the generation and maintenance of phenotypic diversity by affecting the way in which genes are rearranged, regulated and differentially expressed was first made by Britten and Davidson (1969). Recent findings that the primary source of genome-size variation is in fact repetitive DNA (Brenner et al. 1993; Schmidt & Heslop-Harrison 1998; Kidwell 2002) has led to renewed interest in the roles and functions of repetitive loci.
Several recent reviews have highlighted the contribution of repetitive loci in adaptive evolution. Biémont & Vieira (2006) and Volff (2006) focus on transposable elements (TEs), Kashi & King (2006) review the contribution of microsatellite loci and Schmidt & Anderson (2006) review evidence that there is continuity of function across different categories of repetitive loci (including TEs, VNTR, and microsatellites); in the form of a unique capacity for mutation in response to environmental change.
Tracing the evolutionary history of repetitive elements through analysis of nucleotide sequences has revealed that most, if not all, repetitive DNA is derived from TEs: Transposable elements have been identified as the source of satellite repeats in Drosophila and Cetaceans (Kidwell 2002), centromeric repeats have been traced to TEs in plants (Henikoff et al. 2002); palindromic repeats associated with several human diseases have been traced to TE progenitors (Lewis & Cote 2006); and microsatellites have been observed to evolve from TEs in organisms as diverse as fruit flies (Wilder & Hollocher 2001), mosquitoes (Tu et al. 2004), barley (Ramsay et al. 1999) and humans (Deininger & Batzer 2002).
Evidence that transposable elements donate repetitive sequences with unique biological functions to their host organisms (reviewed by Britten 1997; 2006; Biémont & Vieira 2006; Schmidt & Anderson 2006; Volff 2006) provokes questions about the roles and functions of other repetitive DNA loci.
Specific responses to environmental cues have been detected at repetitive loci other than TEs in plants (Ceccarelli et al., 2002), bacteria (Servant, Grandvalet & Mazodier 2000; Kojima & Nakamoto, 2002; Ojaimi et al., 2003) and humans (Uhlemann et al. 2004), indicating that these loci retain the capacity for generation of phenotypic variation, but a direct link between repetitive locus mutation and environmental change is evidenced by only one study to date.
Schmidt & Mitter (2004) grew groups of resistant and susceptible wheat varieties under controlled conditions and genotyped these at microsatellite loci linked to fungal (Fusarium graminearum) resistance, both prior to and following exposure to the pathogen. Within a month of inoculation, 58% of plants had acquired a novel allele at a microsatellite locus mapped to a chromosome containing a major Fusarium resistance gene (Anderson et al., 2001; Buerstmayr et al., 2002, 2003). Observation of the same deletion-based mutation in all varieties, its absence in control plants not exposed to the pathogen, and the detection of no similar mutational events in a control panel of microsatellite loci not linked to fungal resistance, indicates that this example of microsatellite mutation was a site-specific response to a particular external stimulus (Schmidt & Mitter 2004). The design of these experiments was such that mutations were detected in mature parental (floral) tissue only and, as the environmental cue was exposure to a fungal pathogen, this prevented seed-set, meaning heritability of the acquired mutations, and their selection in the next generation, could not be evaluated. Nonetheless, the results provide strong support for the hypothesis that specific environmental cues can induce site-specific mutation at repetitive loci other than transposable elements.
If environmentally induced beneficial RE mutations are to have evolutionary significance, they must also be passed to subsequent generations. Environmentally mediated changes in REs have been reported in a range of taxa, but most well-known examples focus on situations where phenotypic effects are negative (reviewed in Schmidt & Anderson 2006). Little thought seems to have been given to the possibility that such mutations might also have positive adaptive significance in some cases.
Caporale (2000) has indicated that heritable genomic responses to recurrent classes of environmental challenge are in fact a key mechanism of adaptive evolution. Evidence that repetitive DNA elements are at least one source of such mutations is strong:
1. Mutations in and/or transposition of repetitive DNA affect structure and expression of coding genes in many diverse species and play essential roles in fundamental biological processes.
2. REs tend to cluster in genes, or genomic regions, involved in or associated with externally triggered processes and show a unique capacity to respond to environmental signals.
3. Site-specific mutations at and/or transposition of repetitive loci are associated with adaptive changes of phenotype in natural populations.
(Schmidt & Anderson 2006)
Collectively, such findings suggest that genomes are composed of genetic units that are larger, and more complex, than previously recognised. Rather than being determined by simple point mutations in protein-coding regions, most phenotypic variation is generated and maintained by complex combinations of variation within larger metagenes comprised of both coding and non-coding elements. Understanding the individual components of these metagenes, and their contribution to phenotypic variation at the level of the individual, the population and the species offers fascinating and complex new problems for biologists.

by Adele L. Schmidt 1,2
1CSIRO Plant Industry, Queensland Bioscience Precinct, 306 Carmody Road, St Lucia Queensland 4067, Australia
2Department of Zoology, University of Melbourne, Parkville Victoria 3010, Australia

Reprinted with permission