Genetic mosaicism has long been linked to aging, and several hypotheses have been proposed to explain the potential connections between mosaicism and susceptibility to cancer. It has been proposed that mosaicism may disrupt tissue homeostasis by affecting intercellular communications and releasing microenvironmental constraints within tissues. The underlying mechanisms driving these tissue‐level influences remain unidentified, however. Here, we present an evolutionary perspective on the interplay between mosaicism and cancer, suggesting that the tissue‐level impacts of genetic mosaicism can be attributed to Indirect (...) Genetic Effects (IGEs). IGEs can increase the level of cellular stochasticity and phenotypic instability among adjacent cells, thereby elevating the risk of cancer development within the tissue. Moreover, as cells experience phenotypic changes in response to challenging microenvironmental conditions, these changes can initiate a cascade of nongenetic alterations, referred to as Indirect non‐Genetic Effects (InGEs), which in turn catalyze IGEs among surrounding cells. We argue that incorporating both InGEs and IGEs into our understanding of the process of oncogenic transformation could trigger a major paradigm shift in cancer research with far‐reaching implications for practical applications. (shrink)

Enormous phylogenetic variation exists in the number and sizes of introns in protein‐coding genes. Although some consideration has been given to the underlying role of the population‐genetic environment in defining such patterns, the influence of the intracellular environment remains virtually unexplored. Drawing from observations on interactions between co‐transcriptional processes involved in splicing and mRNA 3′‐end formation, a mechanistic model is proposed for splice‐site recognition that challenges the commonly accepted intron‐ and exon‐definition models. Under the suggested model, splicing factors that outcompete (...) 3′‐end processing factors for access to intronic binding sites concurrently favor the recruitment of 3′‐end processing factors at the pre‐mRNA tail. This hypothesis sheds new light on observations such as the intron‐mediated enhancement of gene expression and the negative correlation between intron length and levels of gene expression. (shrink)

Dietary changes can alter the human microbiome with potential detrimental consequences for health. Given that environment, health, and evolution are interconnected, we ask: Could diet‐driven microbiome perturbations have consequences that extend beyond their immediate impact on human health? We address this question in the context of the urgent health challenges posed by global climate change. Drawing on recent studies, we propose that not only can diet‐driven microbiome changes lead to dysbiosis, they can also shape life‐history traits and fuel human evolution. (...) We posit that dietary shifts prompt mismatched microbiome‐host genetics configurations that modulate human longevity and reproductive success. These mismatches can also induce a heritable intra‐holobiont stress response, which encourages the holobiont to re‐establish equilibrium within the changed nutritional environment. Thus, while mismatches between climate change‐related genetic and epigenetic configurations within the holobiont increase the risk and severity of diseases, they may also affect life‐history traits and facilitate adaptive responses. These propositions form a framework that can help systematize and address climate‐related dietary challenges for policy and health interventions. (shrink)