Academic journal article Genetics

Effects of Recombination on Complex Regulatory Circuits

Academic journal article Genetics

Effects of Recombination on Complex Regulatory Circuits

Article excerpt

ABSTRACT

Mutation and recombination are the two main forces generating genetic variation. Most of this variation may be deleterious. Because recombination can reorganize entire genes and genetic circuits, it may have much greater consequences than point mutations. We here explore the effects of recombination on models of transcriptional regulation circuits that play important roles in embryonic development. We show that recombination has weaker deleterious effects on the expression phenotypes of these circuits than mutations. In addition, if a population of such circuits evolves under the influence of mutation and recombination, we find that three key properties emerge: (1) deleterious effects of mutations are reduced dramatically; (2) the diversity of genotypes in the population is greatly increased, a feature that may be important for phenotypic innovation; and (3) cis-regulatory complexes appear. These are combinations of regulatory interactions that influence the expression of one gene and that mitigate deleterious recombination effects.

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MUTATION and recombination are the two main forces generating genetic variation, the raw material that natural selection feeds upon. Although a small fraction of the variation generated by mutation and recombination yields evolutionary innovations, the majority of this variation may be deleterious. Recombination can rearrange entire genes and even larger units of organization. It thus has potentially much greater effects on the phenotype than mutations, in particular point mutations of single nucleotides.

Its potentially large deleterious effects on well-adapted genotypes notwithstanding, recombination is clearly very successful evolutionarily, as the near ubiquity of sexual reproduction in eukaryotes attests (Birky 1996; Judson and Normark 1996; Schon et al. 1998). The reasons for this ubiquity are less clear. (For reviews see Barton and Charlesworth 1998; Otto and Lenormand 2002; Otto and Gerstein 2006.) It is undeniable that sexual reproduction and recombination have clear benefits to individuals or populations. For example, they can help a population avoid the consequences of Muller's ratchet, which is the accumulation of slightly deleterious mutations caused by genetic drift in finite populations (Muller 1964). Second, recombination can help bring together beneficial mutations from different individuals that would otherwise have to arise and go to fixation sequentially in an asexual population (Fisher 1930; Muller 1932). It can thus help speed up adaptive evolution during periods of directional selection where a population is far from a fitness optimum (Keightley and Otto 2006). Additionally, it may cause the more rapid elimination of deleterious mutations (Kondrashov 1998). These and many other benefits of sex may depend on multiple details of how mutations and selection affect the fitness of individuals and the mean fitness of a population. For example, sex can be advantageous for the elimination of deleterious mutations when the combined negative effects of several such mutations on fitness are stronger than the sum or the product of their individual effects (Otto and Feldman 1997; Kondrashov 1998). The question whether these conditions are often met has received considerable attention (Bonhoeffer et al. 2004; Kouyos et al. 2006, 2007; Sanjuan and Elena 2006; Sanjuan et al. 2006).

Against these and other potential advantages of sex stand two major disadvantages. The first is that populations of sexually reproducing and anisogamous organisms are vulnerable to the invasion of asexual variants where only females bear offspring. If an asexual female variant arose that reproduced at the same rate as sexually reproducing females, this variant would double in frequency every generation, because it produces only female offspring. It would thus have a reproductive advantage over sexually reproducing females (Maynard Smith 1978). …

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