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Current Opinion in Genetics & Development

Zijun Sun, Yusuke Toyama
Epithelium undergoes complex deformations during morphogenesis. Many of these deformations rely on the remodelling of apical cell junctions by actomyosin-based contractile force and this has been a major research interest for many years. Recent studies have shown that cells can use additional mechanisms that are not directly driven by actomyosin contractility to alter cell shape and movement, in three-dimensional (3D) space and time. In this review, we focus on a number of these mechanisms, including basolateral cellular protrusion, lateral shift of cell polarity, cytoplasmic flow, regulation of cell volume, and force transmission between cell-cell adhesion and cell-extracellular matrix adhesion, and describe how they underlie Drosophila epithelia deformations...
September 11, 2018: Current Opinion in Genetics & Development
Noah Snyder-Mackler, Amanda J Lea
Both the social and physical environment shape health, reproduction, and survival across many species, and identifying how these effects manifest at the molecular level has long been a priority in medicine and evolutionary biology. The recent rise of functional genomics has enabled researchers to gain new insights into how environmental inputs shape variation in gene regulation, and consequently, downstream organism-level traits. Here, we discuss recent work on this topic, as well as key knowledge gaps. Research in this area spans a wide range of taxa, but we focus our review on mammalian species because of their close evolutionary proximity to humans and because of their relevance for understanding human health...
August 21, 2018: Current Opinion in Genetics & Development
Gillian M Belbin, Maria A Nieves-Colón, Eimear E Kenny, Andres Moreno-Estrada, Christopher R Gignoux
Hispanic/Latino (H/L) populations, although linked by culture and aspects of shared history, reflect the complexity of history and migration influencing the Americas. The original settlement by indigenous Americans, followed by postcolonial admixture from multiple continents, has yielded localized genetic patterns. In addition, numerous H/L populations appear to have signatures of pre-colonization and post-colonization bottlenecks, indicating that tens of millions of H/Ls may harbor signatures of founder effects today...
August 17, 2018: Current Opinion in Genetics & Development
R Marisol Herrera-Perez, Karen E Kasza
Epithelial cell rearrangements and cell shape changes are fundamental mechanisms by which cells build and shape elaborate and diverse tissue architectures from simple tissue sheets. These cell behaviors are regulated by a complex interplay between physical and biochemical mechanisms, many of which have been uncovered in recent studies in Drosophila. While the regulation of these cell behaviors is still under investigation, emerging technologies are being used to gain experimental control over these behaviors, opening new possibilities for designing and engineering tissue structures...
August 10, 2018: Current Opinion in Genetics & Development
Etienne Patin, Lluis Quintana-Murci
Central Africa, a forested region that supports an exceptionally high biodiversity, hosts the world's largest group of hunter-gatherers, who live in close proximity with groups that have adopted agriculture over the past 5000 years. Our understanding of the prehistory of these populations has been dramatically hampered by the almost total absence of fossil remains in this region, a limitation that has recently been circumvented by population genomics approaches. Different studies have estimated that ancestors of rainforest hunter-gatherers and Bantu-speaking farmers separated more than 60 000 years ago, supporting the occurrence of ancient population structure in Africa since the Late Pleistocene...
August 10, 2018: Current Opinion in Genetics & Development
Krishna R Veeramah
There has been an undercurrent of intellectual tension between geneticists studying human population history and archaeologists for almost 40 years. The rapid development of paleogenomics, with geneticists working on the very material discovered by archaeologists, appears to have recently heightened this tension. The relationship between these two fields thus far has largely been of a multidisciplinary nature, with archaeologists providing the raw materials for sequencing, as well as a scaffold of hypotheses based on interpretation of archaeological cultures from which the geneticists can ground their inferences from the genomic data...
August 3, 2018: Current Opinion in Genetics & Development
Guy B Blanchard, Jocelyn Étienne, Nicole Gorfinkiel
We review recent developments in the understanding of the biomechanics of apicomedial actomyosin and how its contractility can tense and deform tissue. Myosin pulses are driven by a biochemical oscillator but how they are modulated by the mechanical context remains unclear. On the other hand, the emergence of tissue behaviour is highly dependent on the material properties of actin, on how strongly components are connected and on the influence of neighbouring tissues. We further review the use of constitutive equations in exploring the mechanics of epithelial apices dominated by apicomedial Myosin contractility...
August 1, 2018: Current Opinion in Genetics & Development
Melissa Ilardo, Rasmus Nielsen
Modern humans inhabit most of earth's harshest environments and display a wide array of lifestyles. Biological adaptations, in addition to technological innovations, have enabled these geographical and cultural explorations. The study of these adaptations helps not only to fundamentally understand our evolution as a species, but also may have increasing relevance as genomics transforms fields such as personalized medicine. Here we review three cultural and environmental shifts that have brought about adaptations in modern humans; the arctic, high altitudes, and a subsistence dependent on breath-hold diving...
August 1, 2018: Current Opinion in Genetics & Development
Jeffrey P Spence, Matthias Steinrücken, Jonathan Terhorst, Yun S Song
Studying how diverse human populations are related is of historical and anthropological interest, in addition to providing a realistic null model for testing for signatures of natural selection or disease associations. Furthermore, understanding the demographic histories of other species is playing an increasingly important role in conservation genetics. A number of statistical methods have been developed to infer population demographic histories using whole-genome sequence data, with recent advances focusing on allowing for more flexible modeling choices, scaling to larger data sets, and increasing statistical power...
July 26, 2018: Current Opinion in Genetics & Development
Niall P Cooke, Shigeki Nakagome
Approximate Bayesian Computation (ABC) is a flexible statistical tool widely applied to addressing a variety of questions regarding the origin and evolution of humans. The significant growth of genomic scale data from diverse geographic populations has facilitated the use of ABC in modelling the complex processes that underlie human demography and local adaptation. However, a fundamental issue still remains in how to efficiently capture patterns of genetic variation with a set of summary statistics in order to achieve better approximation of Bayesian inference...
July 17, 2018: Current Opinion in Genetics & Development
Anna L Gosling, Elizabeth A Matisoo-Smith
Understanding the timing and processes involved in the human settlement of Australia and the Pacific has significance for addressing some key debates relating to human origins and population expansions worldwide. Despite this, for many years, Pacific populations were seriously under-represented in genetic studies of human origins. The last 15 years, however, have seen some major genetic studies involving Australian and Pacific populations which have shed light on their origins and interactions, and the last five years have seen some major developments that are challenging long-held concepts of Pacific settlement...
July 17, 2018: Current Opinion in Genetics & Development
Stephanie L Schnorr
Variation of the human microbiome is a multidimensional value depending on the question of interest. Unlike traditional human genetics, which most often deals with variation at the level of genes or genetic sequences, microbiome variation may be most relevant at the functional level and can be interrogated a number of ways. Most common methods are marker gene metataxonomic surveys or shotgun metagenomic sequencing, however more direct indicators of microbial activity that are gaining popularity include metabolomic and metatranscriptomic surveys...
July 13, 2018: Current Opinion in Genetics & Development
Hidehiko Hashimoto, Edwin Munro
A fundamental challenge in developmental biology is to understand how forces produced by individual cells are patterned in space and time and then integrated to produce stereotyped changes in tissue-level or embryo-level morphology. Ascidians offer a unique opportunity to address this challenge by studying how small groups of cells collectively execute complex, but highly stereotyped morphogenetic movements. Here we highlight recent progress and open questions in the study of ascidian morphogenesis, emphasizing the dynamic interplay of cell fate determination, cellular force generation and tissue-level mechanics...
July 11, 2018: Current Opinion in Genetics & Development
Hiroshi Koyama, Toshihiko Fujimori
Tubular organs and tissues often show various morphological fold patterns in their luminal epithelia. Computational studies have revealed that these patterns could be explained by mechanical deformation of the epithelia. However, experimental validations of this are sparse, and the mechanisms linking genetic and cellular functions to fold mechanics are poorly understood. In the oviduct of the female reproductive tract, the epithelium forms multiple well-aligned straight folds. Disruption of Celsr1, a planar cell polarity-related gene, causes ectopically-branched folds in mice...
July 10, 2018: Current Opinion in Genetics & Development
Connie J Mulligan
Epigenetic variation represents a unique aspect of human biological variation that can shed light on our evolutionary history as well as the etiology of human disease. DNA methylation is the most commonly studied type of epigenetic modification and can alter gene expression without changing the underlying DNA sequence. DNA methylation occurs throughout all living organisms although its function seems to have evolved from genome defense in fungi, bacteria and plants to a more complex role in gene regulation and cellular differentiation in animals...
July 4, 2018: Current Opinion in Genetics & Development
Alice Malivert, Olivier Hamant, Gwyneth Ingram
In land plants, the aerial epidermis is essential for growth control, protection and environmental interactions. Epidermal cell fate is specified early during embryogenesis and maintained throughout plant life. Molecular actors of epidermal specification have been characterized, but how epidermal fate is maintained during growth remains unclear. DEFECTIVE KERNEL 1 (DEK1) is required for epidermal cell fate maintenance during both embryonic and post-embryonic plant development. The activation of a mechanosensitive Ca2+ channel was recently shown to depend on DEK1, suggesting that the interpretation of mechanical cues could be critical for maintaining epidermal cell fate...
July 4, 2018: Current Opinion in Genetics & Development
Hiroyuki Uechi, Erina Kuranaga
The shape and structure of tissues are generated by the dynamic behavior of various cell collectives during morphogenesis. These behaviors include collective cell movement, in which cells move coordinately in a given direction while maintaining cell-cell attachments throughout the collective. For a cell collective to acquire mobility, the cell collective generates forces, and the cells in the front sense extrinsic cues to decide the direction of the movement. However, some collectives that fill a confined space move even though they lack such front cells...
July 4, 2018: Current Opinion in Genetics & Development
Ralf Jauch
Cellular reprogramming using cocktails of transcription factors (TFs) affirms the epigenetic and developmental plasticity of mammalian cells. It demonstrates the ability of TFs to 'read' genetic information and to rewire regulatory networks in different cellular contexts. Silenced chromatin is not an impediment to the genome engagement by ectopically expressed TFs. Reprogramming TFs have been identified in diverse structural families that lack shared domains or sequence motifs. Interestingly, the reprogramming activity of non-redundant paralogous TFs can be switched with a few point mutations...
July 3, 2018: Current Opinion in Genetics & Development
Joaquin Sanz, Haley E Randolph, Luis B Barreiro
Humans display remarkable immune response variation when exposed to identical immune challenges. However, our understanding of the genetic, evolutionary, and environmental factors that impact this inter-individual and inter-population immune response heterogeneity is still in its early days. In this review, we discuss three fundamental questions concerning the recent evolution of the human immune system: the degree to which individuals from different populations vary in their innate immune responses, the genetic variants accounting for such differences, and the evolutionary mechanisms that led to the establishment of these variants in modern human populations...
June 28, 2018: Current Opinion in Genetics & Development
Iosif Lazaridis
I review the evolutionary history of human populations in Europe with an emphasis on what has been learned in recent years through the study of ancient DNA. Human populations in Europe ∼430-39kya (archaic Europeans) included Neandertals and their ancestors, who were genetically differentiated from other archaic Eurasians (such as the Denisovans of Siberia), as well as modern humans. Modern humans arrived to Europe by ∼45kya, and are first genetically attested by ∼39kya when they were still mixing with Neandertals...
June 27, 2018: Current Opinion in Genetics & Development
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