CRISPR-Cas9 genome editing can and has altered human genomes, bringing bioethical debates about this capability to the forefront of philosophical and policy considerations. Here, I consider the underexplored implications of CRISPR-Cas9 gene drives for heritable human genome editing. Modification gene drives applied to heritable human genome editing would introduce a novel form of involuntary eugenic practice that I term guerrilla eugenics. Once introduced into a genome, stealth genetic editing by a gene drive genetic element would occur each subsequent generation irrespective (...) of whether reproductive partners consent to it and irrespective of whether the genetic change confers any benefit. By overriding the ability to ‘opt in’ to genome editing, gene drives compromise the autonomy of carrier individuals and their reproductive partners to choose to use or avoid genome editing and impose additional burdens on those who hope to ‘opt out’ of further genome editing. High incidence of an initially rare gene drive in small human communities could occur within 200 years, with evolutionary fixation globally in a timeframe that is thousands of times sooner than achievable by non-drive germline editing. Following any introduction of heritable gene drives into human genomes, practices intended for surveillance or reversal also create fundamental ethical problems. Current policy guidelines do not comment explicitly on gene drives in humans. These considerations motivate an explicit moratorium as being warranted on gene drive development in heritable human genome editing. (shrink)

It is tempting to invoke organismal selection as perpetually optimizing the function of any given gene. However, natural selection can drive genic functional change without improvement of biochemical activity, even to the extinction of gene activity. Detrimental mutations can creep in owing to linkage with other selectively favored loci. Selection can promote functional degradation, irrespective of genetic drift, when adaptation occurs by loss of gene function. Even stabilizing selection on a trait can lead to divergence of the underlying molecular constituents. (...) Selfish genetic elements can also proliferate independent of any functional benefits to the host genome. Here we review the logic and evidence for these diverse processes acting in genome evolution. This collection of distinct evolutionary phenomena – while operating through easily understandable mechanisms – all contribute to the seemingly counterintuitive notion that maintenance or improvement of a gene's biochemical function sometimes do not determine its evolutionary fate. (shrink)

Recent research has filled many gaps about Caenorhabditis natural history, simultaneously exposing how much remains to be discovered. This awareness now provides means of connecting ecological and evolutionary theory with diverse biological patterns within and among species in terms of adaptation, sexual selection, breeding systems, speciation, and other phenomena. Moreover, the heralded laboratory tractability of C. elegans, and Caenorhabditis species generally, provides a powerful case study for experimental hypothesis testing about evolutionary and ecological processes to levels of detail unparalleled by (...) most study systems. Here, I synthesize pertinent theory with what we know and suspect about Caenorhabditis natural history for salient features of biodiversity, phenotypes, population dynamics, and interactions within and between species. I identify topics of pressing concern to advance Caenorhabditis biology and to study general evolutionary processes, including the key opportunities to tackle problems in dispersal dynamics, competition, and the dimensionality of niche space. (shrink)