Adaptation to high ethanol reveals complex evolutionary pathways

Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts

Endogeneity and the family involvement–firm performance relationship: on the daunting search for instrumental variables

One of the predominant themes in the family business literature is the relationship between family involvement in ownership, management and governance and firm performance. Empirical research in this field is typically plagued by tricky endogeneity problems. From a statistical point of view, endogeneity is a major concern as it violates the central Ordinary Least Squares assumption that the regressor is uncorrelated with the error term, giving rise to inconsistent and biased estimates. A common remedy for this problem is the use of instrumental-variables (IVs) techniques. However, finding suitable IVs that satisfy the conditions of both ‘validity’ and ‘relevance’ is a real challenge. This recurrent difficulty invited us to provide family business scholars with a structured discussion of the problem and to make a number of suggestions for practical solutions, which rely on recent developments in applied econometrics to cope with instruments that turn out to be 'imperfect' and/or 'wea

Exploring open innovation in entrepreneurial private family firms in low- and medium-technology industries

Four cases of open innovation in private family SMEs in low- and medium-technology industries are considered inorder to examine the ways in which family firms can both foster their willingness and use their ability to engage inopen innovation activities. Our cases illustrate how family SMEs can successfully engage in open innovation byhandling multiple and conflicting goals within the family firm in particular ways and by taking up orchestration roleswithin their own open innovation networks to minimize concern for the loss of control

Opvolging van de CEO en eigendomsoverdracht in het familiebedrijf: economische consequenties

status: publishe