PMID- 22355105
OWN - NLM
STAT- MEDLINE
DCOM- 20120504
LR  - 20220310
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 10
DP  - 2012 Mar 6
TI  - Hypervariable loci in the human gut virome.
PG  - 3962-6
LID - 10.1073/pnas.1119061109 [doi]
AB  - Genetic variation is critical in microbial immune evasion and drug resistance, 
      but variation has rarely been studied in complex heterogeneous communities such 
      as the human microbiome. To begin to study natural variation, we analyzed DNA 
      viruses present in the lower gastrointestinal tract of 12 human volunteers by 
      determining 48 billion bases of viral DNA sequence. Viral genomes mostly showed 
      low variation, but 51 loci of  approximately 100 bp showed extremely high variation, so that up 
      to 96% of the viral genomes encoded unique amino acid sequences. Some hotspots of 
      hypervariation were in genes homologous to the bacteriophage BPP-1 viral 
      tail-fiber gene, which is known to be hypermutagenized by a unique 
      reverse-transcriptase (RT)-based mechanism. Unexpectedly, other hypervariable 
      loci in our data were in previously undescribed gene types, including genes 
      encoding predicted Ig-superfamily proteins. Most of the hypervariable loci were 
      linked to genes encoding RTs of a single clade, which we find is the most 
      abundant clade among gut viruses but only a minor component of bacterial RT 
      populations. Hypervariation was targeted to 5'-AAY-3' asparagine codons, which 
      allows maximal chemical diversification of the encoded amino acids while avoiding 
      formation of stop codons. These findings document widespread targeted 
      hypervariation in the human gut virome, identify previously undescribed types of 
      genes targeted for hypervariation, clarify association with RT gene clades, and 
      motivate studies of hypervariation in the full human microbiome.
FAU - Minot, Samuel
AU  - Minot S
AD  - Department of Microbiology, Perelman School of Medicine at the University of 
      Pennsylvania, Philadelphia, PA 19104, USA.
FAU - Grunberg, Stephanie
AU  - Grunberg S
FAU - Wu, Gary D
AU  - Wu GD
FAU - Lewis, James D
AU  - Lewis JD
FAU - Bushman, Frederic D
AU  - Bushman FD
LA  - eng
GR  - UH2 DK083981/DK/NIDDK NIH HHS/United States
GR  - T32AI060516/AI/NIAID NIH HHS/United States
GR  - UH2DK083981/DK/NIDDK NIH HHS/United States
GR  - P30 DK050306/DK/NIDDK NIH HHS/United States
GR  - S10 RR024525/RR/NCRR NIH HHS/United States
GR  - T32 AI060516/AI/NIAID NIH HHS/United States
GR  - R01 AI039368/AI/NIAID NIH HHS/United States
GR  - UL1RR024134/RR/NCRR NIH HHS/United States
GR  - AI39368/AI/NIAID NIH HHS/United States
GR  - S10RR024525/RR/NCRR NIH HHS/United States
GR  - UL1 RR024134/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120221
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Codon)
RN  - 0 (RNA, Ribosomal, 16S)
SB  - IM
MH  - Base Sequence
MH  - Codon
MH  - Contig Mapping
MH  - Gastrointestinal Tract/microbiology/*virology
MH  - *Genetic Variation
MH  - *Genome, Viral
MH  - Humans
MH  - Metagenome
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - Open Reading Frames
MH  - RNA, Ribosomal, 16S/metabolism
MH  - Sequence Analysis, DNA
PMC - PMC3309749
COIS- The authors declare no conflict of interest.
EDAT- 2012/02/23 06:00
MHDA- 2012/05/05 06:00
PMCR- 2012/09/06
CRDT- 2012/02/23 06:00
PHST- 2012/02/23 06:00 [entrez]
PHST- 2012/02/23 06:00 [pubmed]
PHST- 2012/05/05 06:00 [medline]
PHST- 2012/09/06 00:00 [pmc-release]
AID - 1119061109 [pii]
AID - 201119061 [pii]
AID - 10.1073/pnas.1119061109 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3962-6. doi: 
      10.1073/pnas.1119061109. Epub 2012 Feb 21.