title: The Sorcerer II Global Ocean Sampling expedition: expanding the universe of protein families.
abstract: 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.
authors.affiliation: J. Craig Venter Institute, Rockville, Maryland, United States of America. Shibu.Yooseph@venterinstitute.org
authors.forename: Shibu
authors.initials: S
authors.lastname: Yooseph
authors.forename: Granger
authors.initials: G
authors.lastname: Sutton
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Rusch
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Halpern
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Williamson
authors.forename: Karin
authors.initials: K
authors.lastname: Remington
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Eisen
authors.forename: Karla B
authors.initials: KB
authors.lastname: Heidelberg
authors.forename: Gerard
authors.initials: G
authors.lastname: Manning
authors.forename: Weizhong
authors.initials: W
authors.lastname: Li
authors.forename: Lukasz
authors.initials: L
authors.lastname: Jaroszewski
authors.forename: Piotr
authors.initials: P
authors.lastname: Cieplak
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Miller
authors.forename: Huiying
authors.initials: H
authors.lastname: Li
authors.forename: Susan T
authors.initials: ST
authors.lastname: Mashiyama
authors.forename: Marcin P
authors.initials: MP
authors.lastname: Joachimiak
authors.forename: Christopher
authors.initials: C
authors.lastname: van Belle
authors.forename: John-Marc
authors.initials: JM
authors.lastname: Chandonia
authors.forename: David A
authors.initials: DA
authors.lastname: Soergel
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhai
authors.forename: Kannan
authors.initials: K
authors.lastname: Natarajan
authors.forename: Shaun
authors.initials: S
authors.lastname: Lee
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Raphael
authors.forename: Vineet
authors.initials: V
authors.lastname: Bafna
authors.forename: Robert
authors.initials: R
authors.lastname: Friedman
authors.forename: Steven E
authors.initials: SE
authors.lastname: Brenner
authors.forename: Adam
authors.initials: A
authors.lastname: Godzik
authors.forename: David
authors.initials: D
authors.lastname: Eisenberg
authors.forename: Jack E
authors.initials: JE
authors.lastname: Dixon
authors.forename: Susan S
authors.initials: SS
authors.lastname: Taylor
authors.forename: Robert L
authors.initials: RL
authors.lastname: Strausberg
authors.forename: Marvin
authors.initials: M
authors.lastname: Frazier
authors.forename: J Craig
authors.initials: JC
authors.lastname: Venter
mesh_terms: D020224:Expressed Sequence Tags; D009792:Oceans and Seas; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D014871:Water Microbiology
chemical_list: D011506:Proteins