Host genetic determinants of microbiota-dependent nutrition revealed by genome-wide analysis of Drosophila melanogaster

被引:69
作者
Dobson, Adam J. [1 ]
Chaston, John M. [1 ]
Newell, Peter D. [1 ]
Donahue, Leanne [1 ]
Hermann, Sara L. [1 ]
Sannino, David R. [2 ]
Westmiller, Stephanie [1 ]
Wong, Adam C. -N. [1 ]
Clark, Andrew G. [3 ]
Lazzaro, Brian P. [1 ]
Douglas, Angela E. [1 ,3 ]
机构
[1] Cornell Univ, Dept Entomol, Ithaca, NY 14853 USA
[2] Cornell Univ, Dept Microbiol, Ithaca, NY 14853 USA
[3] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA
关键词
GUT MICROBIOTA; NATURAL VARIATION; HOMEOSTASIS; CELL; NEUROBEACHIN; ARCHITECTURE; ASSOCIATION; PROBIOTICS; HOMOLOG;
D O I
10.1038/ncomms7312
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Animals bear communities of gut microorganisms with substantial effects on animal nutrition, but the host genetic basis of these effects is unknown. Here we use Drosophila to demonstrate substantial among-genotype variation in the effects of eliminating the gut microbiota on five host nutritional indices (weight, protein, lipid, glucose and glycogen contents); this includes variation in both the magnitude and direction of microbiota-dependent effects. Genome-wide association studies to identify the genetic basis of the microbiota-dependent variation reveal polymorphisms in largely non-overlapping sets of genes associated with variation in the nutritional traits, including strong representation of conserved genes functioning in signalling. Key genes identified by the GWA study are validated by loss-of-function mutations that altered microbiota-dependent nutritional effects. We conclude that the microbiota interacts with the animal at multiple points in the signalling and regulatory networks that determine animal nutrition. These interactions with the microbiota are probably conserved across animals, including humans.
引用
收藏
页数:7
相关论文
共 51 条
[2]   Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors [J].
Benson, Andrew K. ;
Kelly, Scott A. ;
Legge, Ryan ;
Ma, Fangrui ;
Low, Soo Jen ;
Kim, Jaehyoung ;
Zhang, Min ;
Oh, Phaik Lyn ;
Nehrenberg, Derrick ;
Hua, Kunjie ;
Kachman, Stephen D. ;
Moriyama, Etsuko N. ;
Walter, Jens ;
Peterson, Daniel A. ;
Pomp, Daniel .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (44) :18933-18938
[3]   Slit/Robo Signaling Regulates Cell Fate Decisions in the Intestinal Stem Cell Lineage of Drosophila [J].
Biteau, Benoit ;
Jasper, Heinrich .
CELL REPORTS, 2014, 7 (06) :1867-1875
[4]   Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4 [J].
Böhni, R ;
Riesgo-Escovar, J ;
Oldham, S ;
Brogiolo, W ;
Stocker, H ;
Andruss, BF ;
Beckingham, K ;
Hafen, E .
CELL, 1999, 97 (07) :865-875
[5]   Microbiota-Induced Changes in Drosophila melanogaster Host Gene Expression and Gut Morphology [J].
Broderick, Nichole A. ;
Buchon, Nicolas ;
Lemaitre, Bruno .
MBIO, 2014, 5 (03)
[6]   Gut-associated microbes of Drosophila melanogaster [J].
Broderick, Nichole A. ;
Lemaitre, Bruno .
GUT MICROBES, 2012, 3 (04) :307-321
[7]   Genome-wide association mapping of natural variation in odour-guided behaviour in Drosophila [J].
Brown, E. B. ;
Layne, J. E. ;
Zhu, C. ;
Jegga, A. G. ;
Rollmann, S. M. .
GENES BRAIN AND BEHAVIOR, 2013, 12 (05) :503-515
[8]   IDENTIFICATION OF APHID (HOMOPTERA, APHIDIDAE) SPECIES AND CLONES BY RANDOM AMPLIFIED POLYMORPHIC DNA [J].
CENIS, JL ;
PEREZ, P ;
FERERES, A .
ANNALS OF THE ENTOMOLOGICAL SOCIETY OF AMERICA, 1993, 86 (05) :545-550
[9]   Bacterial Communities of Diverse Drosophila Species: Ecological Context of a Host-Microbe Model System [J].
Chandler, James Angus ;
Lang, Jenna Morgan ;
Bhatnagar, Srijak ;
Eisen, Jonathan A. ;
Kopp, Artyom .
PLOS GENETICS, 2011, 7 (09)
[10]   Innate immune recognition of the microbiota promotes host-microbial symbiosis [J].
Chu, Hiutung ;
Mazmanian, Sarkis K. .
NATURE IMMUNOLOGY, 2013, 14 (07) :668-675