pleiotropy and complexity

    Pleiotropy, the condition when a single mutation in a gene affects multiple distinct phenotypic traits, has bold implications for the development and maintenance of complex organisms.  It has been speculated to motivate a tendency towards cis-regulatory change-bias in morphological evolution (contrasted to actual protein sequence changes), because such regulatory changes exhibit less antagonistic pleiotropy.  Furthermore, such antagonistic pleiotropy is speculated to lie behind the evolution of senescence (the theory posits that alleles beneficial to development and reproduction are deleterious after the reproductive age and cause senescence).  Ultimately, pleiotropy heavily affects morphological evolution through the wide phenotypic effect many SNPs can have on an organism.  Though many authors have asserted that pleiotropy charges organisms a "cost of complexity", Wang et al (2010) poses several reasons for why pleiotropy might not hinder the development of complex forms, and might actually drive it.

    In an effort to explore pleiotropy across a broad phylogenetic scale, the authors compiled five (quite large) datasets in Saccharomyces cerevisiae (3), Caenorhabditis elegans (1), and Mus musculus (1).  In all five datasets the authors observed that most genes affect only a small fraction of traits and only a minority of genes affect many traits--with the median degree of pleiotropy varying from 1-7 in the datasets.  The authors predicted, from their data, that the median number of traits affected by a gene is no greater than a few percent of the total number of traits in an organism. Their observations, along with several others (referenced in the study), indicate a general patter of low pleiotropy in eukaryotes, which disagrees with the assumption of many models which evaluate the effects of such pleiotropy on complex organisms.  Also, their datasets, once evaluated, indicate that gene networks are highly modular (i.e. gene-networks are mechanically insular and largely have much higher within-module effects than between-module effects), and that genes that are highly pleiotropic have high per-trait effects.  These conclusions lead to a different conclusion regarding the 'cost of complexity' than previously indicated by other authors.

    Ultimately, the authors find that three features of pleiotropy/eukaryotes that "substantially alleviate the cost of complexity in adaptive evolution".  They conclude that 1)  as addressed, the lower-than-previously-indicated level of pleiotropy in complex organisms means that mutations do not normally affect many traits simultaneously, 2)  high modularity in gene networks (and gene network memberships) reduces the probability that a random mutation is deleterious ("because the mutation is likely to affect a set of related traits in the same direction rather than a set of unrelated traits in random directions"), and 3) the greater per-trait effect size for more pleiotropic mutations causes a greater probability of fixation and a larger amount of fitness gain when a beneficial mutation occurs in a more complex organism than in a less complex organism.  These conclusions, drawn from five extensive datasets, seem to support the evolution of "moderately-complex" organisms and argue against the conclusions of previous authors which would suggest that pleiotropy stands against the observed biotic complexity in our world.


-Wang, Liao and Zhang (2010). Genomic patterns of pleiotropy and the evolution of complexity. PNAS. 107 (42): 18034-18039
-Williams GC (1957) Pleiotropy, natural selectioon, and the evolution of senescence. Evolution. 11: 398-411