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Transposon Insertion Sequencing, a Global Measure of Gene Function. 转座子插入测序,基因功能的全局测量。
IF 11.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2020-11-23 Epub Date: 2020-09-04 DOI: 10.1146/annurev-genet-112618-043838
Tim van Opijnen, Henry L Levin

The goal of genomics and systems biology is to understand how complex systems of factors assemble into pathways and structures that combine to form living organisms. Great advances in understanding biological processes result from determining the function of individual genes, a process that has classically relied on characterizing single mutations. Advances in DNA sequencing has made available the complete set of genetic instructions for an astonishing and growing number of species. To understand the function of this ever-increasing number of genes, a high-throughput method was developed that in a single experiment can measure the function of genes across the genome of an organism. This occurred approximately 10 years ago, when high-throughput DNA sequencing was combined with advances in transposon-mediated mutagenesis in a method termed transposon insertion sequencing (TIS). In the subsequent years, TIS succeeded in addressing fundamental questions regarding the genes of bacteria, many of which have been shown to play central roles in bacterial infections that result in major human diseases. The field of TIS has matured and resulted in studies of hundreds of species that include significant innovations with a number of transposons. Here, we summarize a number of TIS experiments to provide an understanding of the method and explanation of approaches that are instructive when designing a study. Importantly, we emphasize critical aspects of a TIS experiment and highlight the extension and applicability of TIS into nonbacterial species such as yeast.

基因组学和系统生物学的目标是了解复杂的因素系统如何组合成途径和结构,从而形成活的有机体。理解生物过程的巨大进步源于确定单个基因的功能,这一过程传统上依赖于描述单个突变。DNA测序技术的进步已经为数量惊人且不断增长的物种提供了一整套遗传指令。为了了解这种数量不断增加的基因的功能,一种高通量的方法被开发出来,在一个单一的实验中可以测量整个生物体基因组中基因的功能。这种情况大约发生在10年前,当时高通量DNA测序与转座子介导突变的进展相结合,这种方法被称为转座子插入测序(TIS)。在随后的几年里,TIS成功地解决了有关细菌基因的基本问题,其中许多基因已被证明在导致重大人类疾病的细菌感染中发挥核心作用。TIS领域已经成熟,并对数百个物种进行了研究,其中包括许多转座子的重大创新。在这里,我们总结了一些TIS实验,以提供对方法的理解和方法的解释,这些方法在设计研究时具有指导意义。重要的是,我们强调了TIS实验的关键方面,并强调了TIS在酵母等非细菌物种中的扩展和适用性。
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引用次数: 19
Human genetics. 人类遗传学。
IF 11.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2020-02-02 DOI: 10.1146/annurev.ge.04.120170.000245
V A McKusick
Prerequisites A good knowledge of Catalan and Spanish is indispensable, vehicular languages in which the classes will take place. It is advisable that the students have a good knowledge of English, since many of the information sources of this subject are in this language. It is convenient that the student has achieved basic skills in cell biology, biochemistry and molecular biology. It is convenient that the student knows the basic principles of genetics.
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引用次数: 2
Behavioral Genetics 行为遗传学
IF 11.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2020-02-02 DOI: 10.1002/9780470114735.hawley01624
B. Y C A T H E R I N E B A K
An introduction to how genes and environments interact through development to shape differences in mood, personality, and intelligence A tool to inform public discussion of behavioral genetic research and its broader social implications
介绍基因和环境如何在发展过程中相互作用,形成情绪、个性和智力的差异。这是一种工具,可以为公众讨论行为基因研究及其更广泛的社会影响提供信息
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引用次数: 282
Standard Deviations: The Biological Bases of Transmission Ratio Distortion. 标准偏差:传动比失真的生物学基础。
IF 11.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2019-12-03 DOI: 10.1146/annurev-genet-112618-043905
L. Fishman, Mariah McIntosh
The rule of Mendelian inheritance is remarkably robust, but deviations from the equal transmission of alternative alleles at a locus [a.k.a. transmission ratio distortion (TRD)] are also commonly observed in genetic mapping populations. Such TRD reveals locus-specific selection acting at some point between the diploid heterozygous parents and progeny genotyping and therefore can provide novel insight into otherwise-hidden genetic and evolutionary processes. Most of the classic selfish genetic elements were discovered through their biasing of transmission, but many unselfish evolutionary and developmental processes can also generate TRD. In this review, we describe methodologies for detecting TRD in mapping populations, detail the arenas and genetic interactions that shape TRD during plant and animal reproduction, and summarize patterns of TRD from across the genetic mapping literature. Finally, we point to new experimental approaches that can accelerate both detection of TRD and characterization of the underlying genetic mechanisms. Expected final online publication date for the Annual Review of Genetics, Volume 53 is November 23, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
孟德尔遗传的规律是非常稳健的,但在遗传作图群体中也经常观察到在一个基因座上偏离替代等位基因的平等传递[也称为传递比畸变(TRD)]。这样的TRD揭示了在二倍体杂合子亲本和后代基因分型之间的某个点上起作用的位点特异性选择,因此可以为其他隐藏的遗传和进化过程提供新的见解。大多数经典的自私遗传元素都是通过它们的传播偏差发现的,但许多无私的进化和发育过程也会产生TRD。在这篇综述中,我们描述了在图谱群体中检测TRD的方法,详细介绍了在植物和动物繁殖过程中形成TRD的领域和遗传相互作用,并总结了遗传图谱文献中TRD的模式。最后,我们指出了新的实验方法,可以加速TRD的检测和潜在遗传机制的表征。《遗传学年度评论》第53卷预计最终在线出版日期为2019年11月23日。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。
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引用次数: 36
The Microbiome and Aging. 微生物组与衰老。
IF 11.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2019-12-03 DOI: 10.1146/annurev-genet-112618-043650
Bianca Bana, F. Cabreiro
Aging is a natural process of organismal decay that underpins the development of myriad diseases and disorders. Extensive efforts have been made to understand the biology of aging and its regulation, but most studies focus solely on the host organism. Considering the pivotal role of the microbiota in host health and metabolism, we propose viewing the host and its microbiota as a single biological entity whose aging phenotype is influenced by the complex interplay between host and bacterial genetics. In this review we present how the microbiota changes as the host ages, but also how the intricate relationship between host and indigenous bacteria impacts organismal aging and life span. In addition, we highlight other microbiota-dependent mechanisms that potentially regulate aging, and present experimental animal models for addressing these questions. Importantly, we propose microbiome dysbiosis as an additional hallmark and biomarker of aging. Expected final online publication date for the Annual Review of Genetics, Volume 53 is November 23, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
衰老是一个有机物腐烂的自然过程,是无数疾病和病症发展的基础。人们已经做出了广泛的努力来理解衰老的生物学及其调控,但大多数研究只关注宿主生物。考虑到微生物群在宿主健康和代谢中的关键作用,我们建议将宿主及其微生物群视为一个单一的生物实体,其衰老表型受到宿主和细菌遗传学之间复杂相互作用的影响。在这篇综述中,我们介绍了微生物群如何随着宿主年龄的增长而变化,以及宿主和本土细菌之间的复杂关系如何影响生物体的衰老和寿命。此外,我们强调了其他可能调节衰老的微生物群依赖性机制,并提出了解决这些问题的实验动物模型。重要的是,我们提出微生物组失调是衰老的一个额外标志和生物标志。《遗传学年度评论》第53卷预计最终在线出版日期为2019年11月23日。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。
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引用次数: 110
Cell Size Control in Plants. 植物细胞大小的控制。
IF 11.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2019-12-03 DOI: 10.1146/annurev-genet-112618-043602
Marco D'Ario, R. Sablowski
The genetic control of the characteristic cell sizes of different species and tissues is a long-standing enigma. Plants are convenient for studying this question in a multicellular context, as their cells do not move and are easily tracked and measured from organ initiation in the meristems to subsequent morphogenesis and differentiation. In this article, we discuss cell size control in plants compared with other organisms. As seen from yeast cells to mammalian cells, size homeostasis is maintained cell autonomously in the shoot meristem. In developing organs, vacuolization contributes to cell size heterogeneity and may resolve conflicts between growth control at the cellular and organ levels. Molecular mechanisms for cell size control have implications for how cell size responds to changes in ploidy, which are particularly important in plant development and evolution. We also discuss comparatively the functional consequences of cell size and their potential repercussions at higher scales, including genome evolution. Expected final online publication date for the Annual Review of Genetics, Volume 53 is November 23, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
不同物种和组织的特征细胞大小的遗传控制是一个长期的谜。植物在多细胞环境中便于研究这个问题,因为它们的细胞不移动,并且从分生组织的器官起始到随后的形态发生和分化,很容易被跟踪和测量。在这篇文章中,我们讨论了植物的细胞大小控制与其他生物的比较。从酵母细胞到哺乳动物细胞,茎分生组织的大小平衡是由细胞自主维持的。在发育器官中,空泡化有助于细胞大小的异质性,并可能解决细胞和器官水平上生长控制之间的冲突。细胞大小控制的分子机制涉及细胞大小如何响应倍性的变化,这在植物的发育和进化中尤为重要。我们还比较地讨论了细胞大小的功能后果及其在更高尺度上的潜在影响,包括基因组进化。《遗传学年度评论》第53卷的最终在线出版日期预计为2019年11月23日。修订后的估计数请参阅http://www.annualreviews.org/page/journal/pubdates。
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引用次数: 29
Zebrafish Pigment Pattern Formation: Insights into the Development and Evolution of Adult Form. 斑马鱼色素模式的形成:对成年形态的发展和进化的见解。
IF 11.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2019-12-03 DOI: 10.1146/annurev-genet-112618-043741
Larissa B. Patterson, D. Parichy
Vertebrate pigment patterns are diverse and fascinating adult traits that offer protection from the environment and allow animals to attract mates and avoid predators. Pigment patterns in fish are among the most amenable traits for studying the cellular basis of adult form, as the cells that produce diverse patterns are readily visible in the skin during development. The genetic basis of pigment pattern development has been most studied in the zebrafish, Danio rerio. Zebrafish adults have alternating dark and light horizontal stripes, resulting from the precise arrangement of three main classes of pigment cells: black melanophores, yellow xanthophores, and iridescent iridophores. The coordination of adult pigment cell lineage specification and differentiation with specific cellular interactions and morphogenetic behaviors is necessary for stripe development. Besides providing a nice example of pattern formation responsible for an adult trait of zebrafish, stripe-forming mechanisms also provide a conceptual framework for posing testable hypotheses about pattern diversification more broadly. Here, we summarize what is known about lineages and molecular interactions required for pattern formation in zebrafish, we review some of what is known about pattern diversification in Danio, and we speculate on how patterns in more distant teleosts may have evolved to produce a stunningly diverse array of patterns in nature. Expected final online publication date for the Annual Review of Genetics, Volume 53 is November 23, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
脊椎动物的色素模式是多样而迷人的成年特征,可以保护动物免受环境的侵害,并使动物能够吸引配偶和躲避捕食者。鱼类的色素模式是研究成体细胞基础最合适的特征之一,因为在发育过程中,在皮肤上很容易看到产生不同模式的细胞。色素模式发育的遗传基础在斑马鱼(Danio rerio)中研究得最多。成年斑马鱼有交替的深色和浅色水平条纹,这是由三种主要色素细胞的精确排列造成的:黑色的黑色素细胞、黄色的黄素细胞和彩虹色的色素细胞。成体色素细胞谱系的分化与特定的细胞相互作用和形态发生行为的协调是条纹发育的必要条件。条纹形成机制除了为斑马鱼的成年特征提供了一个很好的模式形成例子外,还为提出更广泛的模式多样化的可测试假设提供了一个概念框架。在这里,我们总结了斑马鱼模式形成所需的已知谱系和分子相互作用,我们回顾了丹尼奥模式多样化的一些已知情况,我们推测了更远的硬骨鱼的模式是如何进化到自然界中产生惊人的多样化模式的。《遗传学年度评论》第53卷的最终在线出版日期预计为2019年11月23日。修订后的估计数请参阅http://www.annualreviews.org/page/journal/pubdates。
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引用次数: 90
Mechanisms of DNA Uptake by Naturally Competent Bacteria. 自然适能细菌摄取DNA的机制。
IF 11.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2019-12-03 DOI: 10.1146/annurev-genet-112618-043641
David Dubnau, Melanie Blokesch

Transformation is a widespread mechanism of horizontal gene transfer in bacteria. DNA uptake to the periplasmic compartment requires a DNA-uptake pilus and the DNA-binding protein ComEA. In the gram-negative bacteria, DNA is first pulled toward the outer membrane by retraction of the pilus and then taken up by binding to periplasmic ComEA, acting as a Brownian ratchet to prevent backward diffusion. A similar mechanism probably operates in the gram-positive bacteria as well, but these systems have been less well characterized. Transport, defined as movement of a single strand of transforming DNA to the cytosol, requires the channel protein ComEC. Although less is understood about this process, it may be driven by proton symport. In this review we also describe various phenomena that are coordinated with the expression of competence for transformation, such as fratricide, the kin-discriminatory killing of neighboring cells, and competence-mediated growth arrest.

转化是细菌中广泛存在的水平基因转移机制。DNA摄取到质周室需要DNA摄取毛和DNA结合蛋白ComEA。在革兰氏阴性菌中,DNA首先通过菌毛的收缩被拉向外膜,然后与质周ComEA结合,起到布朗棘轮的作用,防止向后扩散。类似的机制可能也在革兰氏阳性细菌中起作用,但这些系统的特征不太明显。运输,定义为单链转化DNA到细胞质的运动,需要通道蛋白ComEC。虽然对这一过程的了解较少,但它可能是由质子对称驱动的。在这篇综述中,我们还描述了与转化能力表达相协调的各种现象,如自相残杀、对邻近细胞的亲缘歧视杀死和能力介导的生长停滞。
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引用次数: 103
Genetic Factors in Mammalian Prion Diseases. 哺乳动物朊病毒疾病的遗传因素。
IF 11.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2019-12-03 DOI: 10.1146/annurev-genet-120213-092352
S. Mead, S. Lloyd, J. Collinge
Mammalian prion diseases are a group of neurodegenerative conditions caused by infection of the central nervous system with proteinaceous agents called prions, including sporadic, variant, and iatrogenic Creutzfeldt-Jakob disease; kuru; inherited prion disease; sheep scrapie; bovine spongiform encephalopathy; and chronic wasting disease. Prions are composed of misfolded and multimeric forms of the normal cellular prion protein (PrP). Prion diseases require host expression of the prion protein gene (PRNP) and a range of other cellular functions to support their propagation and toxicity. Inherited forms of prion disease are caused by mutation of PRNP, whereas acquired and sporadically occurring mammalian prion diseases are controlled by powerful genetic risk and modifying factors. Whereas some PrP amino acid variants cause the disease, others confer protection, dramatically altered incubation times, or changes in the clinical phenotype. Multiple mechanisms, including interference with homotypic protein interactions and the selection of the permissible prion strains in a host, play a role. Several non-PRNP factors have now been uncovered that provide insights into pathways of disease susceptibility or neurotoxicity. Expected final online publication date for the Annual Review of Genetics, Volume 53 is November 23, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
哺乳动物朊病毒病是一组由朊病毒感染中枢神经系统引起的神经退行性疾病,包括散发性、变异型和医源性克雅氏病;库鲁病;遗传性朊病毒病;羊痒病;牛海绵状脑病;慢性消耗性疾病。朊病毒是由正常细胞朊蛋白(PrP)的错误折叠和多聚形式组成的。朊病毒疾病需要宿主表达朊蛋白基因(PRNP)和一系列其他细胞功能来支持其繁殖和毒性。遗传形式的朊病毒疾病是由PRNP突变引起的,而获得性和零星发生的哺乳动物朊病毒疾病是由强大的遗传风险和修饰因素控制的。虽然一些PrP氨基酸变异导致疾病,但其他变异赋予保护作用,显著改变潜伏期,或改变临床表型。多种机制,包括干扰同型蛋白相互作用和宿主中允许的朊病毒菌株的选择,发挥了作用。现在已经发现了几个非prnp因素,为疾病易感性或神经毒性的途径提供了见解。《遗传学年度评论》第53卷的最终在线出版日期预计为2019年11月23日。修订后的估计数请参阅http://www.annualreviews.org/page/journal/pubdates。
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引用次数: 57
The foraging Gene and Its Behavioral Effects: Pleiotropy and Plasticity. 觅食基因及其行为效应:立体性和可塑性。
IF 11.1 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2019-12-03 DOI: 10.1146/annurev-genet-112618-043536
I. Anreiter, M. Sokolowski
The Drosophila melanogaster foraging ( for) gene is a well-established example of a gene with major effects on behavior and natural variation. This gene is best known for underlying the behavioral strategies of rover and sitter foraging larvae, having been mapped and named for this phenotype. Nevertheless, in the last three decades an extensive array of studies describing for's role as a modifier of behavior in a wide range of phenotypes, in both Drosophila and other organisms, has emerged. Furthermore, recent work reveals new insights into the genetic and molecular underpinnings of how for affects these phenotypes. In this article, we discuss the history of the for gene and its role in natural variation in behavior, plasticity, and behavioral pleiotropy, with special attention to recent findings on the molecular structure and transcriptional regulation of this gene. Expected final online publication date for the Annual Review of Genetics, Volume 53 is November 23, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
果蝇觅食(for)基因是对行为和自然变异有重大影响的基因的一个公认的例子。这一基因最为人所知的是,它是流浪者和保姆觅食幼虫的行为策略的基础,已被绘制并命名为这种表型。尽管如此,在过去的三十年中,大量的研究描述了在果蝇和其他生物体中,作为一种广泛的表现型的行为调节剂的作用。此外,最近的工作揭示了对如何影响这些表型的遗传和分子基础的新见解。在这篇文章中,我们讨论了for基因的历史及其在行为、可塑性和行为多效性的自然变异中的作用,并特别关注了该基因的分子结构和转录调控的最新发现。《遗传学年度评论》第53卷的最终在线出版日期预计为2019年11月23日。修订后的估计数请参阅http://www.annualreviews.org/page/journal/pubdates。
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引用次数: 45
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Annual review of genetics
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