Constructive Neutral Evolution 20 Years Later.

Evolution has led to a great diversity that ranges from elegant simplicity to ornate complexity. Many complex features are often assumed to be more functional or adaptive than their simpler alternatives. However, in 1999, Arlin Stolzfus published a paper in the Journal of Molecular Evolution that outlined a framework in which complexity can arise through a series of non-adaptive steps. He called this framework Constructive Neutral Evolution (CNE). Despite its two-decade-old roots, many evolutionary biologists still appear to be unaware of this explanatory framework for the origins of complexity. In this perspective piece, we explain the theory of CNE and how it changes the order of events in narratives that describe the evolution of complexity. We also provide an extensive list of cellular features that may have become more complex through CNE. We end by discussing strategies to determine whether complexity arose through neutral or adaptive processes.

Why and how to study genetic changes with context-dependent effects.

The phenotypic impacts of a genetic change can depend on genetic background (e.g. epistasis), as well as other contexts including environment, developmental stage, cell type, disease state, and higher-order combinations thereof. Recent advances in high-throughput phenotyping are uncovering examples of context dependence faster than genotype-phenotype maps and other core concepts are changing to reflect the dynamic nature of biological systems. Here, we review several approaches to study context dependence and their findings. In our opinion, these findings encourage more studies that examine the spectrum of effects a genetic change may have, as opposed to studies that exclusively measure the impact of a genetic change in a particular context. Studies that elucidate the mechanisms that cause the effects of genetic change to vary with context are of special interest. Previous studies of the mechanisms underlying context dependence have improved predictions of phenotype from genotype and have provided insight about how biological systems function and evolve.