Genomic approaches to lifehistory patterns an appraisal

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Genomic analyses of life histories, as reviewed in this chapter, have revealed a number of molecular principles underlying regulation and determination of key life-history events. These can be summarized as follows.

Environmental information (food, crowding, light, daylength, temperature) often modulates life-history traits and this is the basis of phenotypic plasticity. In animals, such information is typically processed by the nervous system, then translated into a hormonal signal, which acts upon signalling pathways to steer gene expressions in target cells. Signalling pathways consist of a membrane-bound extracellular receptor, connected to an intracellular system of kinases, able to trigger a cascade of biochemical events, finally leading to activation of a transcription factor, which then triggers gene expression. The involvement of the insulin signalling pathway in regulating growth, reproduction, and longevity is a prime example of this principle, but also the induction of insect diapause and the developmental switches in polyphenisms act similarly. In plants, phytochromes play a major role in the translation of light signals.

Second, we may note that if an organism has the capacity to follow more than one developmental option, for example a dormancy stage in addition to an active stage, or flowering in addition to vegetative growth, the alternative pathway is often constitutively present throughout life but repressed until an environmental cue triggers its appearance. The execution of the alternative programme then becomes a question of simply removing a repression, rather than staging the whole programme anew. So-called resting stages (e.g. diapause) are not quiescent at all from a molecular point of view. Despite the fact that many genes are downregulated during diapause, the entry, maintenance, and exit of diapause involves active upregulation of several other genes. We have seen indications of such 'hidden' developmental programmes in nematodes (the dauer larva programme) and in Arabidopsis (the floral transition). Interestingly, mutations in

C. elegans show that it is possible to uncouple part of this programme (life extension) from the main pathway leading to dauer formation, and thus to confer increased longevity to the non-dauer adult.

Third, we have seen that expression of life-history traits often comes with intricate mechanisms of regulation that go further than simple transcrip-tional regulation. We have seen four examples of this: alternative splicing, gene silencing, RNAi, and post-translational regulation of protein stability. Alternative splicing was seen in a Drosophila study showing that different splice variants of the same gene are expressed in different life-history stages, and in Arabidopsis, where one of the loci for flowering induction is suppressed by a feedback loop promoting an inactive splice variant of the gene. Alternative splicing seems to be a mechanism by which gene expression can be fine-tuned in time (developmental stage) or space (specific tissues). The second type of non-transcriptional regulation, gene silencing, was observed in the vernalization response of Arabidopsis, where his-tone deacetylation is employed to suppress floral suppression and allow bolting. Gene silencing was also involved in mutations conferring lifespan extension in yeast, nematodes, and fruit flies. Such epigenetic regulation seems to act as a memory of environmental events, which can trigger an adequate response in cells that do not witness the event themselves but are imprinted by their mother cell. The third type of non-transcriptional regulation is RNAi. Both microRNAs (implicated in the photoperiodic pathway of the Arabidopsis floral transition) and RNA-binding proteins (in the autonomous pathway) have been discussed above as means to selectively inhibit mRNAs. Finally, post-translational regulation was noted in the light-dependent stabilization of CONSTANS protein by phytochromes and crytochromes in the photoperiodic pathway regulating flowering time in Arabidopsis.

The fourth molecular principle illustrated in this chapter is that life-history traits are underpinned by a complex network of gene expression and feedback loops. Networks are characterized by upstream and downstream functional units. In the upstream part, a simple trigger may act upon a signalling pathway. If such upstream genes are mutated, this often has very large effects on the phenotype and may introduce a syndrome of correlated altered life-history traits (see the daf-2 mutants of C. elegans). Downstream of the network we often see a host of gene expressions, which are triggered by a limited number of transcription factors, acting upon all genes sharing a certain motif in their promoter. An obvious example of a downstream gene-expression cascade was the microarray analysis of longevity in C. elegans, in which a large number of genes upregulated as well as downregulated by the transcription factor DAF-16 were identified. Another characteristic of a network is the principle of convergence, which holds that different pathways are integrated by acting (some positively, some negatively) on a single integrator gene. The floral repressor FLC, which integrates the autonomous and the vernalization pathway in A. thaliana, is a clear example of this. A third property of networks is redundancy or parallelism. This is especially obvious in organisms with duplicated genomes, where more than one copy of the same gene exists and mutants do not have recognizable phenotypes due to another copy of the gene performing a similar function. The recent discovery of SCHLAFMÜTZE and SCHNARCHZAPFEN in the photoperiodic pathway of Arabidopsis floral transition is a clear example of this.

A final molecular lesson from the examples given in this chapter concerns the extrapolation of genomic information across species. As discussed in Chapter 3, comparative genomics has developed a whole gamut of instruments by which fine- and coarse-scaled comparisons of genomic sequences are made. In this chapter we have seen one example, the photoperiodic response of Arabidopsis and rice, where the genes themselves were conserved between species, but regulated in a different way, with the consequence that Arabidopsis flowering is stimulated by long days and rice flowering is stimulated by short days. If this principle of similar structure but different function in related species is common, homology of coding sequences is insufficient for extrapolating across species; rather, the basis for extrapolation should lie in functional comparative genomics. A similar disparity between the transcriptome and the genome was presented as an example in Chapter 1, when gene expression in different organs of H. sapiens and Pan troglodytes was compared (Fig. 1.7). In the present chapter we have seen that the first methodologies to analyse transcriptional profiles shared across species are now being developed.

Is ecological genomics about to make a major contribution to life-history theory? Obviously the genomics revolution has already intruded into the analysis of life histories, but we see four major limitations. In the first place, the outcomes of microarray studies published so far sometimes differ widely between similar studies. This is especially obvious from the appallingly small overlap of genes reported in different studies to be regulated by age in Drosophila. Maybe what is lacking here is is a good definition of the conditions under which test animals are cultured or exposed. Animal physiologists know that physiological responses of animals are influenced by many environmental factors, some of them difficult to standardize, such as food quality, air humidity, microbial infection, pheromones from conspecifics, etc. Consequently, a genome-wide gene-expression profile may partly reflect such non-standardized aspects of the test organism. Only replication across studies and robust statistical analysis can reveal the universal responses among the ones that are just contingent on specific experimental conditions.

A second limitation is that most of the studies conducted to date have focused on a few genetic model species. Although some generalities have been indicated in the sections above, the regulation of aging though the insulin/IGF-1 signalling pathway being a case in point, most of the work is concentrated on C. elegans, Drosophila, and Arabidopsis, species that represent only a tiny fraction of the array of life histories in nature.

Broadening the comparative basis will surely benefit a further integration of life-history theory and ecological genomics.

A third limitation is the focus on laboratory observation. Because any life history, especially mortality, has an important component external to the organism (predation, microbial infection, competition, spatial heterogeneity), which is difficult to mimic in the laboratory, the relevance of geneexpression profiles and mutants only observed in the laboratory can be doubted. An example illustrating this argument is a study by Weinig et al. (2002), who demonstrated several QTLs for flowering time in Arabidopsis that are only expressed under certain field conditions and thus not found in laboratory mutants. A good strategy for ecological genomics may be to exploit the natural variation of genomic programmes in wild organisms and then to work out mutations and expression profiles relating to these 'eco-variable' loci.

Finally, we note that many gene-expression studies have not yet left the descriptive stage. It is one step to draw up an inventory of transcriptional profiles associated with some life-history event, but quite another to explain the causal relationship between these profiles and the life history. Only in the cases of longevity in C. elegans and flowering time in Arabidopsis is such an understanding coming within reach.

Despite these limitations we see a glorious future for a further merger between ecological genomics and life-history theory. This will involve establishing a link between crucial phenotypic phenomena, such as trade-off and plasticity on the one hand and gene expression, pleiotropy, and molecular signalling on the other. We expect that such bifaceted discussion about fundamental concepts of life-history theory will contribute to a smooth transition between evolutionary explanation, the underlying physiology, and molecular genetics.

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