Sequenciamento do genoma do camundongo demonstra mais diferenças com o genoma humano do que se estimava

Mais distantes – O camundongo (Mus musculus) é o principal modelo animal usado como base para a pesquisa de doenças que atingem o homem, mas até onde vão as semelhanças entre os dois organismos?

Para um grupo internacional de pesquisadores, o melhor entendimento da biologia do camundongo somente seria possível a partir da disponibilidade do genoma completo do roedor. E é justamente isso que acaba de ser concluído.

Em artigo publicado na PLoS Biology, cientistas que compõem o Consórcio para Sequenciamento do Genoma do Camundongo descrevem o sequenciamento e comparam o genoma resultante com o humano. Segundo o estudo, há mais diferenças genéticas do que se imaginava.

Essas grandes diferenças, apontam os pesquisadores, refletem muitas das particularidades que distinguem as duas espécies. Um quinto dos genes do camundongo é composto de cópias novas que surgiram nos últimos 90 milhões de anos.

“Nosso retrato do genoma do camundongo até então estava incompleto. Quando conseguimos juntar todas as peças que faltavam no quebra-cabeça percebemos que estávamos deixando de lado um grande número de genes encontrados apenas no camundongo, e não em humanos”, disse Leo Goodstadt, da Universidade de Oxford, no Reino Unido, um dos autores do estudo.

Do outro lado, o estudo verificou que homem e camundongo têm em comum cerca de 80% de seus genes e a identificação de tais genes amplia diretamente a capacidade de empregar alvos específicos e mais adequados para o estudo de doenças humanas.

O sequenciamento permite distinguir exatamente como separar a biologia humana da biologia do camundongo. Ao preencher as lacunas deixadas por versões anteriores do genoma do roedor da família dos murídeos, os pesquisadores do consórcio conseguiram identificar muitos genes até então desconhecidos.

Na comparação com o mais recente esboço do sequenciamento que foi publicado, o genoma completo apresenta 11.259 genes que são específicos do camundongo – não compartilhados com o homem.

Segundo o estudo, muitos dos genes agora descobertos estão evoluindo em velocidade absolutamente inusitada, provavelmente como resultado de uma espécie de combate evolucionário entre o camundongo e suas células reprodutivas.

“O grande esforço coletivo para completar o sequenciamento valeu a pena. A partir de agora, as novas descobertas que serão feitas permitirão deixar de lado equívocos que vínhamos cometendo e revelar muitos segredos da biologia do camundongo”, disse Deanna Church, dos Institutos Nacionais de Saúde dos Estados Unidos, outra autora da pesquisa.

O artigo Lineage-specific biology revealed by a finished genome assembly of the mouse, de Celia Garcia e outros, pode ser lido clicando aqui.

Para maiores informações transcrevemos, abaixo, o abstract:

Lineage-Specific Biology Revealed by a Finished Genome Assembly of the Mouse
Deanna M. Church1#*, Leo Goodstadt2#*, LaDeana W. Hillier3, Michael C. Zody4,5, Steve Goldstein6, Xinwe She7, Carol J. Bult8, Richa Agarwala1, Joshua L. Cherry1, Michael DiCuccio1, Wratko Hlavina1, Yuri Kapustin1, Peter Meric1, Donna Maglott1, Zoë Birtle2, Ana C. Marques2, Tina Graves3, Shiguo Zhou6, Brian Teague6, Konstantinos Potamousis6, Christopher Churas6, Michael Place9, Jill Herschleb6, Ron Runnheim6, Daniel Forrest6, James Amos-Landgraf10, David C. Schwartz6, Ze Cheng7, Kerstin Lindblad-Toh4,5*, Evan E. Eichler7*, Chris P. Ponting2*, The Mouse Genome Sequencing Consortium¶

1 National Center for Biotechnology Information, Bethesda, Maryland, United States of America, 2 MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, 3 The Genome Center at Washington University, St. Louis, Missouri, United States of America, 4 The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America, 5 Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden, 6 Laboratory for Molecular and Computational Genomics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America, 7 Department of Genome Sciences and Howard Hughes Medical Institute, University of Washington, Seattle, Washington, United States of America, 8 The Jackson Laboratory, Bar Harbor, Maine, United States of America, 9 Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America, 10 McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America

Abstract

The mouse (Mus musculus) is the premier animal model for understanding human disease and development. Here we show that a comprehensive understanding of mouse biology is only possible with the availability of a finished, high-quality genome assembly. The finished clone-based assembly of the mouse strain C57BL/6J reported here has over 175,000 fewer gaps and over 139 Mb more of novel sequence, compared with the earlier MGSCv3 draft genome assembly. In a comprehensive analysis of this revised genome sequence, we are now able to define 20,210 protein-coding genes, over a thousand more than predicted in the human genome (19,042 genes). In addition, we identified 439 long, non–protein-coding RNAs with evidence for transcribed orthologs in human. We analyzed the complex and repetitive landscape of 267 Mb of sequence that was missing or misassembled in the previously published assembly, and we provide insights into the reasons for its resistance to sequencing and assembly by whole-genome shotgun approaches. Duplicated regions within newly assembled sequence tend to be of more recent ancestry than duplicates in the published draft, correcting our initial understanding of recent evolution on the mouse lineage. These duplicates appear to be largely composed of sequence regions containing transposable elements and duplicated protein-coding genes; of these, some may be fixed in the mouse population, but at least 40% of segmentally duplicated sequences are copy number variable even among laboratory mouse strains. Mouse lineage-specific regions contain 3,767 genes drawn mainly from rapidly-changing gene families associated with reproductive functions. The finished mouse genome assembly, therefore, greatly improves our understanding of rodent-specific biology and allows the delineation of ancestral biological functions that are shared with human from derived functions that are not.

Author Summary

The availability of an accurate genome sequence provides the bedrock upon which modern biomedical research is based. Here we describe a high-quality assembly, Build 36, of the mouse genome. This assembly was put together by aligning overlapping individual clones representing parts of the genome, and it provides a more complete picture than previous assemblies, because it adds much rodent-specific sequence that was previously unavailable. The addition of these sequences provides insight into both the genomic architecture and the gene complement of the mouse. In particular, it highlights recent gene duplications and the expansion of certain gene families during rodent evolution. An improved understanding of the mouse genome and thus mouse biology will enhance the utility of the mouse as a model for human disease.

Citation: Church DM, Goodstadt L, Hillier LW, Zody MC, Goldstein S, et al. (2009) Lineage-Specific Biology Revealed by a Finished Genome Assembly of the Mouse. PLoS Biol 7(5): e1000112. doi:10.1371/journal.pbio.1000112

Academic Editor: Richard J. Roberts, New England Biolabs, United States of America

Received: December 19, 2008; Accepted: April 3, 2009; Published: May 26, 2009

This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

Funding: DMC, RA, JC, MD, DM, WH, YK, and the National Institutes of Health Intramural Sequencing Center were supported by the Intramural Research Program of the NIH. CPP, ZB, and LG were supported by the UK Medical Research Council. ACM was supported by the Swiss National Science Foundation. EEE, XS, and ZC were supported in part by National Institutes of Health grant HG002385. EEE is an investigator of the Howard Hughes Medical Institute. The Genome Center at Washington University, The Human Genome Sequencing Center at the Baylor College of Medicine, and The Broad Institute of Harvard and MIT are supported by genome sequencing grants from National Human Genome Research Institute. Chromosomes 2, 4, 11 and X were completed with funding from the Wellcome Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: EST, expressed sequence tag; ncRNA, noncoding RNA; SSR, simple sequence repeat; TPF, tiling path file; VR, vomeronasal receptors; WGSA, Whole Genome Sequence and Assembly

* E-mail: church{at}ncbi.nlm.nih.gov (DMC); plos{at}llew.org.uk (LG); kersli{at}broad.mit.edu (KL-T); eee{at}gs.washington.edu (EEE); chris.ponting{at}dpag.ox.ac.uk (CPP)

# These authors contributed equally to this work.

¶ Membership of The Mouse Genome Sequencing Consortium is provided in the Acknowledgments.

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Matéria da Agência FAPESP, publicada pelo EcoDebate, com informações complementares, 28/05/2008.

[EcoDebate, 28/05/2009]

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