Catálogo de publicaciones - revistas

<jats:p>The spread of modern humans across the globe has led to genetic adaptations to diverse local environments. Recent developments in genomic technologies, statistical analyses, and expanded sampled populations have led to improved identification and fine-mapping of genetic variants associated with adaptations to regional living conditions and dietary practices. Ongoing efforts in sequencing genomes of indigenous populations, accompanied by the growing availability of “-omics” and ancient DNA data, promises a new era in our understanding of recent human evolution and the origins of variable traits and disease risks.</jats:p>

<jats:p>Heritability has traditionally been thought to be a characteristic feature of the genetic material of an organism—notably, its DNA. However, it is now clear that inheritance not based on DNA sequence exists in multiple organisms, with examples found in microbes, plants, and invertebrate and vertebrate animals. In mammals, the molecular mechanisms have been challenging to elucidate, in part due to difficulties in designing robust models and approaches. Here we review some of the evidence, concepts, and potential mechanisms of non–DNA sequence–based transgenerational inheritance. We highlight model systems and discuss whether phenotypes are replicated or reconstructed over successive generations, as well as whether mechanisms operate at transcriptional and/or posttranscriptional levels. Finally, we explore the short- and long-term implications of non–DNA sequence–based inheritance. Understanding the effects of non–DNA sequence–based mechanisms is key to a full appreciation of heritability in health and disease.</jats:p>

<jats:p>Cells of the immune system routinely respond to cues from their local environment and feed back to their surroundings through transient responses, choice of differentiation trajectories, plastic changes in cell state, and malleable adaptation to their tissue of residence. Genomic approaches have opened the way for comprehensive interrogation of such orchestrated responses. Focusing on genomic profiling of transcriptional and epigenetic cell states, we discuss how they are applied to investigate immune cells faced with various environmental cues. We highlight some of the emerging principles on the role of dense regulatory circuitry, epigenetic memory, cell type fluidity, and reuse of regulatory modules in achieving and maintaining appropriate responses to a changing environment. These provide a first step toward a systematic understanding of molecular circuits in complex tissues.</jats:p>

<jats:p>The rising prevalences of type 2 diabetes and obesity constitute major threats to human health globally. Powerful social and economic factors influence the distribution of these diseases among and within populations. These factors act on a substrate of individual predisposition derived from the composite effects of inherited DNA variation and a range of environmental exposures experienced throughout the life course. Although “Western” lifestyle represents a convenient catch-all culprit for such exposures, effective treatment and prevention will be informed by characterization of the most critical, causal environmental factors. In this Review, we examine how burgeoning understanding of the genetic basis of type 2 diabetes and obesity can highlight nongenetic exposures that drive development of these conditions.</jats:p>