Todays genome projects aim at elucidating the function of all genes in a genome to eventually obtain a complete knowledge of all genetic pathways in a cell and an organism. However, targeted mutations of genes do not always reveal phenotypes. Also, there are a large proportion of fast evolving genes in eukaryotic organisms, which do not appear to have been detected by classic genetic screens (1, 2). This could partially be explained by a high degree of redundancy between gene functions (3, 4). However, another explanation comes from population genetical theory. In a large population, very weak selection coefficients are sufficient to fix alleles of genes which convey an adaptive advantage. The exact relationship can be derived from Kimuras theory of neutral evolution, which states that adaptation can take effect when the fitness difference conveyed by a new allele is larger than 1/(2 Ne) (Ne is the effective population size).Thus, it is possible that there are genes that have only a small effect on the fitness of an individual, but are nonetheless important for long term fitness within a population. Since typical laboratory experiments look only at individual fitness, the full function of these genes can not be elucidated. In fact, this consideration applies for all genes, even to those which have strong effects on the phenotype of individuals. Even for those it is likely that they have additional aspects of function which can only be revealed, if fitness is measured within the framework of a larger reference population. At its limit, one has to conclude that the understanding of the full function of a gene requires to set up experiments that involve the entire living population of a species. Any experiment smaller than that would imply a remaining uncertainty towards the true function of a gene. In my talk I will present the concrete examples that suggest that these considerations are true and suggest new experimental approaches.

1.      Schmid & Tautz, PNAS 94, 9746 (1997)
2.      Tautz & Schmid, Proc Roy Soc B 353, 231 (1998)
3.      Tautz, Bioessays 14, 263 (1992)
4.      Novak et al.,  Nature 388, 167 (1997)

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