The majority of animal genes are required for wild-type fitness

Cell
Arun K RamaniAndrew G Fraser

Abstract

Almost all eukaryotic genes are conserved, suggesting that they have essential functions. However, only a minority of genes have detectable loss-of-function phenotypes in experimental assays, and multiple theories have been proposed to explain this discrepancy. Here, we use RNA-mediated interference in C. elegans to examine how knockdown of any gene affects the overall fitness of worm populations. Whereas previous studies typically assess phenotypes that are detectable by eye after a single generation, we monitored growth quantitatively over several generations. In contrast to previous estimates, we find that, in these multigeneration population assays, the majority of genes affect fitness, and this suggests that genetic networks are not robust to mutation. Our results demonstrate that, in a single environmental condition, most animal genes play essential roles. This is a higher proportion than for yeast genes, and we suggest that the source of negative selection is different in animals and in unicellular eukaryotes.

References

Nov 6, 1998·Nature·L Timmons, A Fire
Nov 21, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·S L Rutherford
Dec 15, 2000·Trends in Ecology & Evolution·Z Yang, J P Bielawski
Mar 10, 2001·Science·J L HartmanL Hartwell
Jun 29, 2001·Nature·A E Hirsh, H B Fraser
Jul 26, 2002·Nature·Guri GiaeverMark Johnston
Aug 15, 2002·Trends in Genetics : TIG·Laurence D Hurst
Nov 26, 2002·Proceedings of the National Academy of Sciences of the United States of America·Maitreya J DunhamDavid Botstein
Feb 26, 2003·Genes & Development·Joris PothofMarcel Tijsterman
Nov 19, 2003·PLoS Biology·Lincoln D SteinRobert H Waterston
Dec 6, 2003·Genome Research·Asher D CutterMelissa Dellos
Feb 7, 2004·Science·Amy Hin Yan TongCharles Boone
Mar 27, 2004·Molecular Biology and Evolution·Nicolas Bierne, Adam Eyre-Walker
May 8, 2004·Nature Reviews. Genetics·Laurence D HurstMartin J Lercher
Nov 3, 2004·Nature Reviews. Genetics·Hiroaki Kitano
Feb 22, 2005·Nature Genetics·Ran KafriYitzhak Pilpel
Apr 1, 2005·Proceedings of the National Academy of Sciences of the United States of America·Dennis P WallMarcus W Feldman
Apr 19, 2006·Nature Reviews. Genetics·Csaba PálMartin J Lercher
Aug 31, 2006·Nature Genetics·David DeutscherEytan Ruppin
Jan 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Caroline SchmitzHarald Hutter
May 19, 2007·Nature Reviews. Genetics·Charles BooneBrenda J Andrews
Sep 21, 2007·Molecular Systems Biology·Hiroaki Kitano
Sep 28, 2007·Journal of Biology·Alexandra B ByrnePeter J Roy
Nov 21, 2007·WormBook : the Online Review of C. Elegans Biology·Kenneth Kemphues
Dec 1, 2007·WormBook : the Online Review of C. Elegans Biology·Theresa Stiernagle
Apr 19, 2008·Science·Maureen E HillenmeyerGuri Giaever
Jul 16, 2008·Nature Methods·David K BreslowJonathan S Weissman
Nov 17, 2009·Nucleic Acids Research·Todd W HarrisPaul W Sternberg
Jan 23, 2010·Science·Michael CostanzoCharles Boone
Apr 24, 2010·Science·Robin D DowellCharles Boone

❮ Previous
Next ❯

Citations

Jul 16, 2013·Nature Methods·Eviatar YeminiWilliam R Schafer
Jan 17, 2014·Proceedings. Biological Sciences·Jeremy C Gray, Asher D Cutter
Apr 12, 2014·Molecular Biology and Evolution·Wei-Chin Ho, Jianzhi Zhang
Apr 30, 2014·Annual Review of Genomics and Human Genetics·Wilfried Haerty, Chris P Ponting
Dec 3, 2015·Critical Reviews in Biochemistry and Molecular Biology·Tianzuo Zhan, Michael Boutros
Apr 10, 2013·Current Opinion in Biotechnology·K A Geiler-SamerotteM L Siegal
Jan 23, 2015·Environmental Science & Technology·Sang-Kyu JungWeiwei Zhong
Oct 9, 2013·Journal of Molecular Evolution·Richard Jovelin
Jan 2, 2015·Scientific Reports·Daniel SchottCraig P Hunter
Oct 9, 2016·Plant Science : an International Journal of Experimental Plant Biology·Martine Devic, Thomas Roscoe
Apr 8, 2017·Journal of Evolutionary Biology·M T RutterA E Strand
Nov 10, 2017·PLoS Genetics·June H Tan, Andrew G Fraser
Jun 4, 2019·The Plant Journal : for Cell and Molecular Biology·Matthew T RutterAllan E Strand
Sep 13, 2014·G3 : Genes - Genomes - Genetics·Xinyang BingThomas J S Merritt
Oct 17, 2017·Nature Reviews. Genetics·Giulia RancatiNorman Pavelka
Jul 22, 2018·Evolutionary Applications·Gregoire LeroyJinliang Wang
Jul 20, 2019·Nature Communications·Jörn M SchmiedelBen Lehner

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.