The Sorcerer II Global Ocean Sampling expedition: expanding the universe of protein families.
Metagenomics projects based on shotgun sequencing of populations of micro-organisms yield insight into protein families. We used sequence similarity clustering to explore proteins with a comprehensive dataset consisting of sequences from available databases together with 6.12 million proteins predicted from an assembly of 7.7 million Global Ocean Sampling (GOS) sequences. The GOS dataset covers nearly all known prokaryotic protein families. A total of 3,995 medium- and large-sized clusters consisting of only GOS sequences are identified, out of which 1,700 have no detectable homology to known families. The GOS-only clusters contain a higher than expected proportion of sequences of viral origin, thus reflecting a poor sampling of viral diversity until now. Protein domain distributions in the GOS dataset and current protein databases show distinct biases. Several protein domains that were previously categorized as kingdom specific are shown to have GOS examples in other kingdoms. About 6,000 sequences (ORFans) from the literature that heretofore lacked similarity to known proteins have matches in the GOS data. The GOS dataset is also used to improve remote homology detection. Overall, besides nearly doubling the number of current proteins, the predicted GOS proteins also add a great deal of diversity to known protein families and shed light on their evolution. These observations are illustrated using several protein families, including phosphatases, proteases, ultraviolet-irradiation DNA damage repair enzymes, glutamine synthetase, and RuBisCO. The diversity added by GOS data has implications for choosing targets for experimental structure characterization as part of structural genomics efforts. Our analysis indicates that new families are being discovered at a rate that is linear or almost linear with the addition of new sequences, implying that we are still far from discovering all protein families in nature.
Yooseph
Shibu
S
J. Craig Venter Institute, Rockville, Maryland, United States of America. Shibu.Yooseph@venterinstitute.org
Sutton
Granger
G
Rusch
Douglas B
DB
Halpern
Aaron L
AL
Williamson
Shannon J
SJ
Remington
Karin
K
Eisen
Jonathan A
JA
Heidelberg
Karla B
KB
Manning
Gerard
G
Li
Weizhong
W
Jaroszewski
Lukasz
L
Cieplak
Piotr
P
Miller
Christopher S
CS
Li
Huiying
H
Mashiyama
Susan T
ST
Joachimiak
Marcin P
MP
van Belle
Christopher
C
Chandonia
John-Marc
JM
Soergel
David A
DA
Zhai
Yufeng
Y
Natarajan
Kannan
K
Lee
Shaun
S
Raphael
Benjamin J
BJ
Bafna
Vineet
V
Friedman
Robert
R
Brenner
Steven E
SE
Godzik
Adam
A
Eisenberg
David
D
Dixon
Jack E
JE
Taylor
Susan S
SS
Strausberg
Robert L
RL
Frazier
Marvin
M
Venter
J Craig
JC
D020224:Expressed Sequence Tags; D009792:Oceans and Seas; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D014871:Water Microbiology
D011506:Proteins