Trends in Genetics最新文献

N6-methyladenosine (m6A) regulates retrotransposon activity, shifting between repression and activation across different species and developmental stages. It promotes RNA decay, sequestration, or stability, influencing genome integrity, adaptation, and disease. This article explores the dual role of m6A in retrotransposon control, highlighting its evolutionary significance in genome regulation and cellular differentiation.

LINE-1 (long interspersed nuclear element 1, L1) retrotransposons constitute ~17% of human DNA (~0.5 million genomic L1 copies) and exhibit context-dependent expression in different cell lines. Recent studies reveal that L1 is under multilayered control by diverse factors that either collaborate or compete with each other to ensure precise L1 activity. Remarkably, L1s have been co-opted as various transcription-dependent regulatory elements, such as promoters, enhancers, and topologically associating domain (TAD) boundaries, that regulate gene expression in zygotic genome activation, aging, cancer, and other disorders. This review highlights the regulation of L1 and its regulatory functions that influence disease and development.

DNA methylation clocks, which measure biological age by analyzing age-related DNA methylation patterns, offer powerful biomarkers of aging. But as a recent preprint highlights, current models underperform in diverse populations. The next generation of clocks must prioritize equity to avoid reinforcing disparities in precision aging and disease risk prediction.

Metabolites are chemically heterogeneous and difficult to quantify in easily read formats. Recently, Tan and Fraser demonstrated that metabolites can be readily quantified by pairing aptamer function with DNA sequencing. This reflects a larger trend of sequencing for assessing biomolecule abundances, further leading to sequencing being a universal analytical tool.

How does genomic information unfold, to give rise to self-constructing living organisms with problem-solving capacities at all levels of organization? We review recent progress that unifies work in developmental genetics and machine learning (ML) to understand mapping of genes to traits. We emphasize the deep symmetries between evolution and learning, which cast the genome as instantiating a generative model. The layer of physiological computations between genotype and phenotype provides a powerful degree of plasticity and robustness, not merely complexity and indirect mapping, which strongly impacts individual and evolutionary-scale dynamics. Ideas from ML and neuroscience now provide a versatile, quantitative formalism for understanding what evolution learns and how developmental and regenerative morphogenesis interpret the deep lessons of the past to solve new problems. This emerging understanding of the informational architecture of living material is poised to impact not only genetics and evolutionary developmental biology but also regenerative medicine and synthetic morphoengineering.

MicroRNAs (miRNAs) are key regulators of gene expression and control cellular functions in physiological and pathophysiological states. miRNAs play important roles in disease, stress, and development, and are now being investigated for therapeutic approaches. Alternative processing of miRNAs during biogenesis results in the generation of miRNA isoforms (isomiRs) which further diversify miRNA gene regulation. Single-cell RNA-sequencing (scsRNA-seq) technologies, together with computational strategies, enable exploration of miRNAs, isomiRs, and interacting RNAs at the cellular level. By integration with other miRNA-associated single-cell modalities, miRNA roles can be resolved at different stages of processing and regulation. In this review we discuss (i) single-cell experimental assays that measure miRNA and isomiR abundances, and (ii) computational methods for their analysis to investigate the mechanisms of miRNA biogenesis and post-transcriptional regulation.

Genetic databases drive research by enabling open access. Recently, parties to the Convention on Biological Diversity agreed on new rules for sharing benefits from the use of digital sequence information (DSI) which upholds open access, and also imposed new requirements for data depositors, database managers, and users.

Human accelerated regions (HARs) are the fastest-evolving sequences in the human genome since the divergence from chimpanzees. Some of these regions are suspected to have contributed to the evolution of unique human brain features. Recently, Cui et al. conducted a large-scale study identifying which HARs may have influenced neuronal function.

Handedness (i.e., the preference to use either the left or the right hand for fine motor tasks) is a widely investigated trait. Handedness heritability is consistently estimated to be 25%. After decades of research, recent large-scale genome-wide association and exome sequencing studies have identified multiple genes associated with handedness and highlighted tubulin genes. Tubulin genes play a role in several processes during brain development that may be relevant for handedness ontogenesis, including axon guidance, axon growth, and forming the inner structure of motile cilia. Moreover, tubulin genes are associated with several psychiatric disorders. This finding therefore may offer insights into biological pathways mediating the link between handedness, brain asymmetries, and psychiatric traits.

How does the genome encode the form of the organism? What is the nature of this genomic code? Inspired by recent work in machine learning and neuroscience, we propose that the genome encodes a generative model of the organism. In this scheme, by analogy with variational autoencoders (VAEs), the genome comprises a connectionist network, embodying a compressed space of 'latent variables', with weights that get encoded by the learning algorithm of evolution and decoded through the processes of development. The generative model analogy accounts for the complex, distributed genetic architecture of most traits and the emergent robustness and evolvability of developmental processes, while also offering a conception that lends itself to formalization.