Quantifying fitness distributions and phenotypic relationships in recombinant yeast populations

doi:10.1073/pnas.0704037104

Quantifying fitness distributions and phenotypic relationships in recombinant yeast populations

*Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138;
^§Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138; and
^†Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA 02142

Contributed by Stuart L. Schreiber, May 2, 2007 (received for review August 31, 2006)

Abstract

Studies of the role of sex in evolution typically involve a longitudinal comparison of a single ancestor to several intermediate descendants and to one terminally evolved descendant after many generations of adaptation under a given selective regime. Here we take a complementary, statistical approach to sex in evolution, by describing the distribution of phenotypic similarity in a population of yeast F₁ meiotic recombinants. By applying graph theory to fitness measurements of thousands of Saccharomyces cerevisiae recombinants treated with 10 mechanistically distinct, growth-inhibitory small-molecule perturbagens (SMPs), we show that the network of phenotypic similarity among F₁ recombinants exhibits a scale-free degree distribution. F₁ recombinants are often phenotypically unique and sometimes exceptional, and their fitness strengths are unevenly distributed across the 10 compound treatments. By contrast, highly phenotypically similar F₁ recombinants constitute failing hubs that display below-average fitness across all compound treatments and are candidate substrates for purifying selection. Comparison of the F₁ generation with the parental strains reveals that (i) there is a specialist more fit in any given single condition than any of the parents but (ii) only rarely are there generalists that exhibit greater fitness than both parental strains across a majority of conditions. This analysis allows us to evaluate and to gain better theoretical understanding of the costs and benefits of sex in the F₁ generation.

Footnotes

^‡To whom correspondence may be addressed. E-mail: perlst{at}fas.harvard.edu, deeds{at}fas.harvard.edu, or stuart_schreiber{at}harvard.edu
Author contributions: E.O.P. and E.J.D. contributed equally to this work; E.O.P. and E.J.D. designed research; E.O.P. and E.J.D. performed research; E.O.P., E.J.D., E.I.S., and S.L.S. contributed new reagents/analytic tools; E.O.P., E.J.D., O.A., E.I.S., and S.L.S. analyzed data; and E.O.P., E.J.D., E.I.S., and S.L.S. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0704037104/DC1.
Abbreviations:

SMPs,

small-molecule perturbagens;

TBR,

true benefit ratio;

GC,

giant component.