The influence of genetics on future crop production strategies: from traits to genes, and genes to traits

This paper discusses how a genetical approach to plant physiology can contribute to research underpinning the production of new crop varieties. It highlights the interactions between genetics and plant breeding and how the current advances in genetics and the new science of genomics can contribute to our understanding of the genetical control of key agronomic traits ‐ the process of ‘translating’ traits to identified and mapped genes. Advances in genomics, such as the sequencing of whole genomes and expressed sequence tags, are producing information on genes and gene structures, but without knowing their function. A great deal more biology will be necessary to translate gene structure to function ‐ the process of translating genes to traits. Combining these ‘forward’ and ‘reverse’ genetic approaches will allow us to get comprehensive knowledge of the biology of agronomic traits at the physiological, biochemical and molecular levels, so that the ‘circuitry’ of our crop plants can be elucidated. This will enable plant breeders to manipulate crop phenotype using marker‐assisted breeding or genetic engineering approaches with a precision not previously possible.     

MicroRNA 与肿瘤的研究进展

microRNA是近年来发现的与基因表达调控相关的一类非编码小分子单链RNA,长度约21-22个碱基对构成,通过与靶mRNA碱基对特异结合,引起靶mRNA降解或翻译抑制,调控基因转录后的表达。microRNA通过干预基因表达,从而对细胞的分化、增殖、凋亡、新陈代谢等多项生命活动进行调控。microRNA的表达异常可以引起细胞的分化、增殖、凋亡的异常,这与肿瘤的发生、发展关系密切。其作为一个新的分子生物学标志,在肿瘤的诊断、治疗中有着重要的潜在价值。     

World of small RNAs: from ribozymes to siRNA and miRNA

RNAs, besides bridging genetic information to proteins, the major determinants of bio-structures and functions, serve as active regulators of gene expression. Initiated nearly 20 years ago with ribozymes (the small RNAs with catalytic activity providing fine tuning of gene expression and function, used as molecular scissors and tools for gene discovery), an era of more complex and coordinated gene regulation by small RNAs, siRNA, and miRNA has recently started. Simple nucleotide complementarity results in highly ordered and regulated events, such as assembly of RNA and proteins, resulting in gene silencing either by mRNA degradation or suppression of translation. This article reviews our contributions to the understanding of structure, the function of small RNAs, their use in biotechnology, and the understanding of phenotypes such as apoptosis, metastasis, and differentiation.     

Using single‐cell genomics to understand developmental processes and cell fate decisions

High‐throughput ‐omics techniques have revolutionised biology, allowing for thorough and unbiased characterisation of the molecular states of biological systems. However, cellular decision‐making is inherently a unicellular process to which “bulk” ‐omics techniques are poorly suited, as they capture ensemble averages of cell states. Recently developed single‐cell methods bridge this gap, allowing high‐throughput molecular surveys of individual cells. In this review, we cover core concepts of analysis of single‐cell gene expression data and highlight areas of developmental biology where single‐cell techniques have made important contributions. These include understanding of cell‐to‐cell heterogeneity, the tracing of differentiation pathways, quantification of gene expression from specific alleles, and the future directions of cell lineage tracing and spatial gene expression analysis.     

Improved understanding of gene expression regulation using systems biology

This article reviews the current state of systems biology approaches, including the experimental tools used to generate ‘omic’ data and computational frameworks to interpret this data. Through illustrative examples, systems biology approaches to understand gene expression and gene expression regulation are discussed. Some of the challenges facing this field and the future opportunities in the systems biology era are highlighted.     

The Piwi‐piRNA pathway: road to immortality

Despite its medical, social, and economic significance, understanding what primarily causes aging, that is, the mechanisms of the aging process, remains a fundamental and fascinating problem in biology. Accumulating evidence indicates that a small RNA‐based gene regulatory machinery, the Piwi‐piRNA pathway, represents a shared feature of nonaging (potentially immortal) biological systems, including the germline, somatic cancer stem cells, and certain ‘lower’ eukaryotic organisms like the planarian flatworm and freshwater hydra. The pathway primarily functions to repress the activity of mobile genetic elements, also called transposable elements (TEs) or ‘jumping genes’, which are capable of moving from one genomic locus to another, thereby causing insertional mutations. TEs become increasingly active and multiply in the genomes of somatic cells as the organism ages. These characteristics of TEs highlight their decisive mutagenic role in the progressive disintegration of genetic information, a molecular hallmark associated with aging. Hence, TE‐mediated genomic instability may substantially contribute to the aging process.     

Mitochondria and metazoan epigenesis

In eukaryotes, mitochondrial activity controls ATP production, calcium dynamics, and redox state, thereby establishing physiological parameters governing the transduction of biochemical signals that regulate nuclear gene expression. However, these activities are commonly assumed to fulfill a ‘housekeeping’ function: necessary for life, but an epiphenomenon devoid of causal agency in the developmental flow of genetic information. Moreover, it is difficult to perturb mitochondrial function without generally affecting cell viability. For these reasons little is known about the extent of mitochondrial influence on gene activity in early development. Recent discoveries pertaining to the redox regulation of key developmental signaling systems together with the fact that mitochondria are often asymmetrically distributed in animal embryos suggests that they may contribute spatial information underlying differential specification of cell fate. In many cases such asymmetries correlate with localization of genetic determinants (i.e., mRNAs or proteins), particularly in embryos that rely heavily on cell-autonomous means of cell fate specification. In such embryos the localized genetic determinants play a dominant role, and any developmental information contributed by the mitochondria themselves is likely to be less obvious and more difficult to isolate experimentally. Hence, ‘regulative’ embryos that make more extensive use of conditional cell fate specification are better suited to experimental investigation of mitochondrial impacts on developmental gene regulation. Recent studies of the sea urchin embryo, which is a paradigmatic example of such a system, suggest that anisotropic distribution of mitochondria provides a source gradient of spatial information that directs epigenetic specification of the secondary axis via Nodal–Lefty signaling.     

Gene therapy for peripheral arterial disease

Our understanding of the molecular biology of vascular disease is rapidly expanding, and this scientific growth has brought with it new opportunities for therapeutic intervention at the molecular and genetic levels. Although our tools for genetic manipulation in vivo and our knowledge of potential molecular targets are still crude and incomplete, the early application of these concepts to clinical problems is already underway, both in the pre-clinical and clinical arenas. The treatment of peripheral vascular disease, although greatly improved over recent decades by surgical and minimally-invasive techniques, remains limited by vascular proliferative lesions and by our inability to modulate the progression of native disease. This review explores some of the evolving concepts of therapeutic gene manipulation and their initial application in the peripheral circulation.