Mutational Pleiotropy and the Strength of Stabilizing Selection Within and Between
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A Comprehensive Study of Metabolite Genetics Reveals Strong Pleiotropy and Heterogeneity Across Time and Context
ARTICLE https://doi.org/10.1038/s41467-019-12703-7 OPEN A comprehensive study of metabolite genetics reveals strong pleiotropy and heterogeneity across time and context Apolline Gallois1,12, Joel Mefford2,12, Arthur Ko 3, Amaury Vaysse 1, Hanna Julienne1, Mika Ala-Korpela4,5,6,7,8,9, Markku Laakso 10, Noah Zaitlen2,12*, Päivi Pajukanta 3,12*& Hugues Aschard 1,11,12* 1234567890():,; Genetic studies of metabolites have identified thousands of variants, many of which are associated with downstream metabolic and obesogenic disorders. However, these studies have relied on univariate analyses, reducing power and limiting context-specific under- standing. Here we aim to provide an integrated perspective of the genetic basis of meta- bolites by leveraging the Finnish Metabolic Syndrome In Men (METSIM) cohort, a unique genetic resource which contains metabolic measurements, mostly lipids, across distinct time points as well as information on statin usage. We increase effective sample size by an average of two-fold by applying the Covariates for Multi-phenotype Studies (CMS) approach, identifying 588 significant SNP-metabolite associations, including 228 new associations. Our analysis pinpoints a small number of master metabolic regulator genes, balancing the relative proportion of dozens of metabolite levels. We further identify associations to changes in metabolic levels across time as well as genetic interactions with statin at both the master metabolic regulator and genome-wide level. 1 Department of Computational Biology - USR 3756 CNRS, Institut Pasteur, Paris, France. 2 Department of Medicine, University of California, San Francisco, CA, USA. 3 Department of Human Genetics, University of California, Los Angeles, CA, USA. -
An Introgression Analysis of Quantitative Trait Loci That Contribute to a Morphological Difference Between Drosophila Simulans and D
Copyight 0 1997 by the Genetics Societv of America An Introgression Analysis of Quantitative Trait Loci That Contribute to a Morphological Difference Between Drosophila simulans and D. mauritiana Cathy C. Laurie, John R. True, Jianjun Liu and John M. Mercer Department of Zoology, Duke University, Durham, North Carolina 27708 Manuscript received August 12, 1996 Accepted for publication October 29, 1996 ABSTRACT Drosophila simulans and D. maum'tiana differ markedly in morphology of the posterior lobe, a male- specific genitalic structure. Bothsize and shapeof the lobe can be quantifiedby a morphometric variable, PC1, derived from principal components and Fourier analyses. The genetic architectureof the species difference in PC1 was investigated previously by composite interval mapping, which revealed largely additive inheritance, with a minimum of eight quantitative trait loci (QTL) affecting the trait. This analysis was extended by introgression of marked segments of the maun'tiana third chromosome into a simulans background by repeated backcrossing. Thetwo types of experiment are consistentin suggesting that several QTL on the third chromosome may have effects in the range of 10-15% of the parental difference andthat all or nearly all QTL have effects in the same direction. Since the parental difference is large (30.4 environmental standard deviations), effects of this magnitude can produce alternative homozygotes with little overlap in phenotype. However, these estimates may not reflect the effects of individual loci, since each interval or introgressed segment may contain multiple QTL. The consistent direction of allelic effects suggests a history of directional selection on the posterior lobe. HE genetic analysis of a quantitative trait usually ual genes that affect continuously variable traits. -
Evolution by Natural Selection, Formulated Independently by Charles Darwin and Alfred Russel Wallace
UNIT 4 EVOLUTIONARY PATT EVOLUTIONARY E RNS AND PROC E SS E Evolution by Natural S 22 Selection Natural selection In this chapter you will learn that explains how Evolution is one of the most populations become important ideas in modern biology well suited to their environments over time. The shape and by reviewing by asking by applying coloration of leafy sea The rise of What is the evidence for evolution? Evolution in action: dragons (a fish closely evolutionary thought two case studies related to seahorses) 22.1 22.4 are heritable traits that with regard to help them to hide from predators. The pattern of evolution: The process of species have changed evolution by natural and are related 22.2 selection 22.3 keeping in mind Common myths about natural selection and adaptation 22.5 his chapter is about one of the great ideas in science: the theory of evolution by natural selection, formulated independently by Charles Darwin and Alfred Russel Wallace. The theory explains how T populations—individuals of the same species that live in the same area at the same time—have come to be adapted to environments ranging from arctic tundra to tropical wet forest. It revealed one of the five key attributes of life: Populations of organisms evolve. In other words, the heritable characteris- This chapter is part of the tics of populations change over time (Chapter 1). Big Picture. See how on Evolution by natural selection is one of the best supported and most important theories in the history pages 516–517. of scientific research. -
Microevolution and the Genetics of Populations Microevolution Refers to Varieties Within a Given Type
Chapter 8: Evolution Lesson 8.3: Microevolution and the Genetics of Populations Microevolution refers to varieties within a given type. Change happens within a group, but the descendant is clearly of the same type as the ancestor. This might better be called variation, or adaptation, but the changes are "horizontal" in effect, not "vertical." Such changes might be accomplished by "natural selection," in which a trait within the present variety is selected as the best for a given set of conditions, or accomplished by "artificial selection," such as when dog breeders produce a new breed of dog. Lesson Objectives ● Distinguish what is microevolution and how it affects changes in populations. ● Define gene pool, and explain how to calculate allele frequencies. ● State the Hardy-Weinberg theorem ● Identify the five forces of evolution. Vocabulary ● adaptive radiation ● gene pool ● migration ● allele frequency ● genetic drift ● mutation ● artificial selection ● Hardy-Weinberg theorem ● natural selection ● directional selection ● macroevolution ● population genetics ● disruptive selection ● microevolution ● stabilizing selection ● gene flow Introduction Darwin knew that heritable variations are needed for evolution to occur. However, he knew nothing about Mendel’s laws of genetics. Mendel’s laws were rediscovered in the early 1900s. Only then could scientists fully understand the process of evolution. Microevolution is how individual traits within a population change over time. In order for a population to change, some things must be assumed to be true. In other words, there must be some sort of process happening that causes microevolution. The five ways alleles within a population change over time are natural selection, migration (gene flow), mating, mutations, or genetic drift. -
Investigations Into Roles for Endocytosis in LIN-12/Notch
Investigations into roles for endocytosis in LIN-12/Notch signaling and its regulation Jessica Chan Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy under the Executive Committee of the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2020 © 2020 Jessica Chan All Rights Reserved Abstract The LIN-12/Notch signaling pathway is highly conserved in all animals, and is crucial for proper development. It is a key pathway in specifying cell fate in many cellular contexts, and dysregulation of the pathway can have deleterious consequences. Therefore, understanding how LIN-12/Notch signaling is regulated in different contexts has been a main area of interest in the field. Previous studies in different model organisms have identified many modes of regulation of the signaling pathway, one of which is endocytosis of the ligand and receptor. Here, I further investigated the role of endocytosis in LIN-12/Notch signaling in multiple developmental contexts in Caenorhabditis elegans. Work in Drosophila and vertebrates had previously established that ligand-mediated activation of Notch requires ubiquitination of the intracellular domain of the transmembrane ligand and the activity of the endocytic adaptor Epsin in the signaling cell. The consensus in the field is that Epsin-mediated endocytosis of mono-ubiquitinated ligand generates a pulling force that exposes a cleavage site in Notch for an ADAM protease, a critical step in signal transduction. In contrast, in this thesis, I examined two different transmembrane ligands in several different cell contexts and found that activation of LIN-12/Notch and the paralogous GLP-1/Notch in C. -
Nicotinic Receptor Alpha7 Expression During Tooth Morphogenesis Reveals Functional Pleiotropy
Nicotinic Receptor Alpha7 Expression during Tooth Morphogenesis Reveals Functional Pleiotropy Scott W. Rogers1,2*, Lorise C. Gahring1,3 1 Geriatric Research, Education and Clinical Center, Veteran’s Administration, Salt Lake City, Utah, United States of America, 2 Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah, United States of America, 3 Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, United States of America Abstract The expression of nicotinic acetylcholine receptor (nAChR) subtype, alpha7, was investigated in the developing teeth of mice that were modified through homologous recombination to express a bi-cistronic IRES-driven tau-enhanced green fluorescent protein (GFP); alpha7GFP) or IRES-Cre (alpha7Cre). The expression of alpha7GFP was detected first in cells of the condensing mesenchyme at embryonic (E) day E13.5 where it intensifies through E14.5. This expression ends abruptly at E15.5, but was again observed in ameloblasts of incisors at E16.5 or molar ameloblasts by E17.5–E18.5. This expression remains detectable until molar enamel deposition is completed or throughout life as in the constantly erupting mouse incisors. The expression of alpha7GFP also identifies all stages of innervation of the tooth organ. Ablation of the alpha7-cell lineage using a conditional alpha7Cre6ROSA26-LoxP(diphtheria toxin A) strategy substantially reduced the mesenchyme and this corresponded with excessive epithelium overgrowth consistent with an instructive role by these cells during ectoderm patterning. However, alpha7knock-out (KO) mice exhibited normal tooth size and shape indicating that under normal conditions alpha7 expression is dispensable to this process. -
Patterns and Power of Phenotypic Selection in Nature
Articles Patterns and Power of Phenotypic Selection in Nature JOEL G. KINGSOLVER AND DAVID W. PFENNIG Phenotypic selection occurs when individuals with certain characteristics produce more surviving offspring than individuals with other characteristics. Although selection is regarded as the chief engine of evolutionary change, scientists have only recently begun to measure its action in the wild. These studies raise numerous questions: How strong is selection, and do different types of traits experience different patterns of selection? Is selection on traits that affect mating success as strong as selection on traits that affect survival? Does selection tend to favor larger body size, and, if so, what are its consequences? We explore these questions and discuss the pitfalls and future prospects of measuring selection in natural populations. Keywords: adaptive landscape, Cope’s rule, natural selection, rapid evolution, sexual selection henotypic selection occurs when individuals with selection on traits that affect survival stronger than on those Pdifferent characteristics (i.e., different phenotypes) that affect only mating success? In this article, we explore these differ in their survival, fecundity, or mating success. The idea and other questions about the patterns and power of phe- of phenotypic selection traces back to Darwin and Wallace notypic selection in nature. (1858), and selection is widely accepted as the primary cause of adaptive evolution within natural populations.Yet Darwin What is selection, and how does it work? never attempted to measure selection in nature, and in the Selection is the nonrandom differential survival or repro- century following the publication of On the Origin of Species duction of phenotypically different individuals. -
An Introduction to Quantitative Genetics I Heather a Lawson Advanced Genetics Spring2018 Outline
An Introduction to Quantitative Genetics I Heather A Lawson Advanced Genetics Spring2018 Outline • What is Quantitative Genetics? • Genotypic Values and Genetic Effects • Heritability • Linkage Disequilibrium and Genome-Wide Association Quantitative Genetics • The theory of the statistical relationship between genotypic variation and phenotypic variation. 1. What is the cause of phenotypic variation in natural populations? 2. What is the genetic architecture and molecular basis of phenotypic variation in natural populations? • Genotype • The genetic constitution of an organism or cell; also refers to the specific set of alleles inherited at a locus • Phenotype • Any measureable characteristic of an individual, such as height, arm length, test score, hair color, disease status, migration of proteins or DNA in a gel, etc. Nature Versus Nurture • Is a phenotype the result of genes or the environment? • False dichotomy • If NATURE: my genes made me do it! • If NURTURE: my mother made me do it! • The features of an organisms are due to an interaction of the individual’s genotype and environment Genetic Architecture: “sum” of the genetic effects upon a phenotype, including additive,dominance and parent-of-origin effects of several genes, pleiotropy and epistasis Different genetic architectures Different effects on the phenotype Types of Traits • Monogenic traits (rare) • Discrete binary characters • Modified by genetic and environmental background • Polygenic traits (common) • Discrete (e.g. bristle number on flies) or continuous (human height) -
Synthetic Morphogenesis
Downloaded from http://cshperspectives.cshlp.org/ on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Synthetic Morphogenesis Brian P. Teague, Patrick Guye, and Ron Weiss Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Correspondence: [email protected] Throughout biology, function is intimately linked with form. Across scales ranging from subcellular to multiorganismal, the identity and organization of a biological structure’s subunits dictate its properties. The field of molecular morphogenesis has traditionally been concerned with describing these links, decoding the molecular mechanisms that give rise to the shape and structure of cells, tissues, organs, and organisms. Recent advances in synthetic biology promise unprecedented control over these molecular mechanisms; this opens the path to not just probing morphogenesis but directing it. This review explores several frontiers in the nascent field of synthetic morphogenesis, including programmable tissues and organs, synthetic biomaterials and programmable matter, and engineering complex morphogenic systems de novo. We will discuss each frontier’s objectives, current approaches, constraints and challenges, and future potential. hat is the underlying basis of biological 2014). As the mechanistic underpinnings of Wstructure? Speculations were based on these processes are elucidated, opportunities macroscopic observation until the 17th century, arise to use this knowledge to direct mor- when Antonie van Leeuwenhoek and Robert phogenesis toward novel, useful ends. We call Hooke discovered that organisms were com- this emerging field of endeavor “synthetic mor- posed of microscopic cells (Harris 1999), and phogenesis.” Inspired by and based on natural that the size and shape of the cells affected the morphogenic systems, synthetic morphogenesis properties of the structures they formed. -
Impact of Epistasis and Pleiotropy on Evolutionary Adaptation
Downloaded from rspb.royalsocietypublishing.org on June 22, 2011 Impact of epistasis and pleiotropy on evolutionary adaptation Bjørn Østman, Arend Hintze and Christoph Adami Proc. R. Soc. B published online 22 June 2011 doi: 10.1098/rspb.2011.0870 Supplementary data "Data Supplement" http://rspb.royalsocietypublishing.org/content/suppl/2011/06/18/rspb.2011.0870.DC1.h tml References This article cites 72 articles, 18 of which can be accessed free http://rspb.royalsocietypublishing.org/content/early/2011/06/18/rspb.2011.0870.full.ht ml#ref-list-1 P<P Published online 22 June 2011 in advance of the print journal. Subject collections Articles on similar topics can be found in the following collections evolution (2744 articles) Receive free email alerts when new articles cite this article - sign up in the box at the top Email alerting service right-hand corner of the article or click here Advance online articles have been peer reviewed and accepted for publication but have not yet appeared in the paper journal (edited, typeset versions may be posted when available prior to final publication). Advance online articles are citable and establish publication priority; they are indexed by PubMed from initial publication. Citations to Advance online articles must include the digital object identifier (DOIs) and date of initial publication. To subscribe to Proc. R. Soc. B go to: http://rspb.royalsocietypublishing.org/subscriptions This journal is © 2011 The Royal Society Downloaded from rspb.royalsocietypublishing.org on June 22, 2011 Proc. R. Soc. B doi:10.1098/rspb.2011.0870 Published online Impact of epistasis and pleiotropy on evolutionary adaptation Bjørn Østman1,2,3,*, Arend Hintze1,3,4 and Christoph Adami1,2,3 1Keck Graduate Institute of Applied Life Sciences, Claremont, CA 91711, USA 2Microbiology and Molecular Genetics, 3BEACON Center for the Study of Evolution in Action, and 4Department of Computer Science and Engineering, Michigan State University, East Lansing, MI 48823, USA Evolutionary adaptation is often likened to climbing a hill or peak. -
Principles of Differentiation and Morphogenesis
Swarthmore College Works Biology Faculty Works Biology 2016 Principles Of Differentiation And Morphogenesis Scott F. Gilbert Swarthmore College, [email protected] R. Rice Follow this and additional works at: https://works.swarthmore.edu/fac-biology Part of the Biology Commons Let us know how access to these works benefits ouy Recommended Citation Scott F. Gilbert and R. Rice. (2016). 3rd. "Principles Of Differentiation And Morphogenesis". Epstein's Inborn Errors Of Development: The Molecular Basis Of Clinical Disorders On Morphogenesis. 9-21. https://works.swarthmore.edu/fac-biology/436 This work is brought to you for free by Swarthmore College Libraries' Works. It has been accepted for inclusion in Biology Faculty Works by an authorized administrator of Works. For more information, please contact [email protected]. 2 Principles of Differentiation and Morphogenesis SCOTT F. GILBERT AND RITVA RICE evelopmental biology is the science connecting genetics with transcription factors, such as TFHA and TFIIH, help stabilize the poly anatomy, making sense out of both. The body builds itself from merase once it is there (Kostrewa et al. 2009). Dthe instructions of the inherited DNA and the cytoplasmic system that Where and when a gene is expressed depends on another regula interprets the DNA into genes and creates intracellular and cellular tory unit of the gene, the enhancer. An enhancer is a DNA sequence networks to generate the observable phenotype. Even ecological fac that can activate or repress the utilization of a promoter, controlling tors such as diet and stress may modify the DNA such that different the efficiency and rate of transcription from that particular promoter. -
Why Do Cave Fish Lose Their Eyes? How Evolution Can Lead to Losing Abilities As Well As Gaining Them
Why Do Cave Fish Lose Their Eyes? How evolution can lead to losing abilities as well as gaining them This StepRead is based on an article provided by the American Museum of Natural History. There are caves deep under the ground where the sun never shines. The only light that enters these caves is from the headlamps of cave explorers. If you went inside of one of these caves and turned off your headlamp, you would see nothing at all. There would be no shadows or shapes, just blackness. In some of these caves, there are organisms that live without light. They include salamanders, crustaceans, and fishes. In fact, more than one hundred species of cave fishes live in darkness for their whole lives. They depend on senses other than sight to hunt, eat, and reproduce. Carlsbad Caverns National Park These fishes have evolved, or developed over many generations, to live without light. Many of these species of fishes are blind or nearly blind. Some of them don’t even have eyes. Yet they all evolved from fishes that could see. Somehow, over millions of years, these fishes both lost the ability to see and gained the ability to live without sight. How did that happen? How can evolution cause a species to lose a trait? It’s a mystery that scientists have been trying to solve. Their search for an answer gives us a fascinating look at how evolution works. Regressive Evolution We usually think of evolution as a process in which species gain new traits. But in cave fishes we have an example of regressive evolution.