Genome sequence of Synechococcus CC9311: Insights
into adaptation to a coastal environment
Brian Palenik*, Qinghu Ren†, Chris L. Dupont*, Garry S. Myers†, John F. Heidelberg†, Jonathan H. Badger†,
Ramana Madupu†, William C. Nelson†, Lauren M. Brinkac†, Robert J. Dodson†, A. Scott Durkin†, Sean C. Daugherty†,
Stephen A. Sullivan†, Hoda Khouri†, Yasmin Mohamoud†, Rebecca Halpin†, and Ian T. Paulsen†‡
*Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92093; and†The Institute for Genomic Research,
Rockville, MD 20850
Edited by Robert Haselkorn, University of Chicago, Chicago, IL, and approved July 10, 2006 (received for review April 11, 2006)
Coastal aquatic environments are typically more highly productive
and dynamic than open ocean ones. Despite these differences,
cyanobacteria from the genus Synechococcus are important pri-
mary producers in both types of ecosystems. We have found that
the genome of a coastal cyanobacterium, Synechococcus sp. strain
CC9311, has significant differences from an open ocean strain,
Synechococcus sp. strain WH8102, and these are consistent with
the differences between their respective environments. CC9311
has a greater capacity to sense and respond to changes in its
(coastal) environment. It has a much larger capacity to transport,
store, use, or export metals, especially iron and copper. In contrast,
phosphate acquisition seems less important, consistent with the
higher concentration of phosphate in coastal environments.
CC9311 is predicted to have differences in its outer membrane
lipopolysaccharide, and this may be characteristic of the speciation
horizontally transferred genes are markedly different between the
coastal and open ocean genomes and suggest a more prominent
role for phages in horizontal gene transfer in oligotrophic
cyanobacteria ? genomics ? marine
nutrients from deeper depths and inputs from land and sedi-
ments. The higher nutrient concentrations lead to higher pri-
mary productivity. The spectral quality of light is typically
different because of the presence of terrestrial material and algal
biomass. These conditions contrast strongly with the low-
nutrient blue-light-dominated ecosystems of the open ocean.
Although each coastal environment has unique elements, these
generalizations help us understand the adaptations likely to be
found in coastal compared to open ocean microorganisms.
Some adaptations of photosynthetic microorganisms to the
open ocean vs. coastal environment have included adaptations
vs. open ocean Synechococcus have been well documented (1–4).
In terms of nutrients, Carpenter (5) noted that coastal phyto-
plankton (diatom) species had a higher Ks (half-saturation
constant for transport) for nitrate, whereas related open ocean
diatom species had a lower Ks. The minimum amount of iron and
other metals for growth of open ocean phytoplankton is less than
that needed for coastal species, suggesting that adaptation to in
situ metal levels is a significant factor in phytoplankton specia-
tion (6–8). Recently, it has been shown, again in diatoms, that
adaptation to low iron in the open ocean involves changes in the
cellular concentration of the iron-rich photosynthetic reaction
center proteins of photosystem I (9) and the use of plastocyanin,
a copper containing protein, instead of iron (10).
We report here the genome sequence of Synechococcus sp.
strain CC9311. This organism was isolated from the edge of
California Current after nitrate enrichment and low light incu-
bation (11). Strains related to CC9311 have been isolated from
oastal waters typically have higher nutrient concentrations
than open ocean waters because of wind-driven upwelling of
coastal environments such as Vineyard Sound (12, 13) and have
been highly represented in rpoC gene sequence libraries of
Southern California coastal waters and in the water column of
the California Current when it displayed a coastal type chloro-
phyll profile (ref. 14; B.P., unpublished work). CC9311 possesses
an ability to adapt to light quality (blue to green light ratios) not
seen in open ocean Synechococcus strains such as WH8102,
further indicating a coastal ecosystem niche for this strain (12).
The availability of the genome sequence of CC9311 (Fig. 1)
allows us to compare it to the genome sequence of Synechococ-
cus sp. strain WH8102 (15), an open ocean strain, and to begin
to understand the adaptation of bacterial genomes to the coastal
vs. open ocean environments.
Results and Discussion
Gene Regulation and Two-Component Regulatory Systems. One of
the insights from the genome of the open ocean Synechococcus
WH8102 was that it and other open ocean cyanobacteria have
minimal regulatory systems, particularly two-component regu-
latory systems consisting of a sensor and response regulator pair
(15–17). There are only five histidine kinase sensors and nine
response regulators in WH8102, and it was suggested that this
was due to adaptation to a relatively constant ecosystem. As one
would predict from adaptation to the more variable coastal
environment, CC9311 has nearly double this number, with 11
histidine kinase sensors and 17 response regulators (Fig. 2).
Interestingly, these additional systems occur in pairs in the
genome, which is not always the case in WH8102. The function
of these sensors is not predictable from their sequences at this
time but may regulate the more complex metal metabolism in
Despite the presence of additional sensor kinases, based on
BLAST and phylogenetic analyses, CC9311 apparently lacks a
phosphate sensor-response regulator system seen in other cya-
nobacteria and bacteria in general (18). Consistent with this,
several alkaline phosphatases present in WH8102 are absent,
and CC9311 has fewer periplasmic phosphate-binding proteins
used in ABC transporter systems. These differences between the
open ocean and coastal Synechococcus types likely reflect the
higher phosphate concentrations in coastal environments com-
pared to some surface ocean environments where phosphate can
Metals and CC9311. CC9311 has a number of metal enzymes or
cofactors not found in WH8102, suggesting that it has a greater
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The sequence reported in this paper has been deposited in the GenBank
database (accession no. CP000435). The Synechococcus CC9311 strain has been deposited
in the Provasoli–Guillard National Center for Culture of Marine Phytoplankton (http:??
ccmp.bigelow.org) under catalog no. CCMP2515.
‡To whom correspondence should be addressed. E-mail: email@example.com.
© 2006 by The National Academy of Sciences of the USA
September 5, 2006 ?
vol. 103 ?
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use for iron (Fig. 3). This is consistent with higher metal quotas
(6), and adds a mechanistic basis to these previous studies.
Iron-dependent metalloenzymes unique to CC9311 include a
cytochrome P450-like encoding ORF (sync?2424), two addi-
tional cytochrome c molecules (sync?1753 and sync?1742), and
one or two additional ferrodoxins (sync?1953 and sync?0980, the
latter truncated). It also has a putative iron-dependent alcohol
CC9311 appears to have a greater use for copper than
WH8102, because it has a copper zinc superoxide dismutase
not seen in marine cyanobacteria (sync?1771) until this work
(CC9902 and CC9605; http:??genome.jgi-psf.org?mic?home.
html). It has a putative multicopper oxidase (sync?1489), which
could be involved in oxidation of organic compounds or detox-
ifying high levels of reduced copper (19). Interestingly, it has
same clade as CC9311, was more resistant to copper than
oligotrophic strains (20) .
For other metal usage, there appears to be a putative vana-
dium-dependent bromoperoxidase (sync?2681). The latter gene
is very interesting, because it is highly similar to one in marine
red algae. In red algae, this enzyme generates brominated
compounds using hydrogen peroxide (21, 22). Cyanobacteria
have been shown to produce brominated compounds such as
bromodiphenyl ethers through an unknown mechanism, with the
best-studied case being a filamentous cyanobacterial symbiont of
a sponge (23). These brominated compounds have been found
recently to cause leakage of fungal cell membranes (24), but the
role of brominated compounds, if any, in CC9311 is open to
Possibly because of its more intensive use of metals, CC9311
has some metal transporters not seen in WH8102, including an
FeoA?B transporter for iron(II) (sync?0681-0682). Total iron
concentrations are higher in coastal environments, and reduced
iron(II) may be more abundant as well, because it is likely
produced from photochemical reactions of iron and organic
matter (25, 26). CC9311 also has three cation-dependent efflux
transporters (sync?0686, sync?1861, and sync?1510) compared to
two in WH8102, suggesting that it may have an increased
capacity to export toxic metal levels if needed.
In contrast, the oligotrophic ocean strain WH8102 has systems
predicted for the efflux of arsenite (preceded by its reduction)
and chromate (15) that are not found in CC9311. It has been
suggested that high arsenate to phosphate ratios in oligotrophic
regions result in the need of microorganisms to deal with excess
Coastal Synechococcus strain CC9311 has a greatly enhanced
a gene for bacterial metallothionein (sync?1081, sync?2426,
sync?0853, and sync?2379) compared to one in Synechococcus
WH8102 and none in some Prochlorococcus strains. Gene am-
plification of smtA has been found in freshwater Synechococcus
PCC6301 in response to higher trace metal levels such as
cadmium (28). However, in this case, smtA copies occur in
tandem, not disbursed throughout the genome as seen in
CC9311 also has a greatly enhanced capacity specifically for
iron storage. It has five copies of bacterial ferritin (sync?0854,
sync?0687, sync?1077, sync?1539, and sync?0680) compared to
one in most cyanobacterial genomes including Synechococcus
WH8102. It also has a ferritin-related protein DpsA (DNA-
later is not found in WH8102 but is found in some Prochloro-
coccus strains (PMT2218 in MIT9313).
It is unclear whether the greatly enhanced transport and metal
storage capacity for iron and other metals in CC9311 is due to
a greater need for metals, the need to respond to excess metal
levels, or the possibility that the cells see episodic metal con-
centrations. Iron concentrations in California coastal environ-
ments can vary from limiting to replete with rapid fluctuations
(29), thus the ability to store iron may be advantageous. Taken
together, these results suggest a much more metal-dependent
ecological strategy for CC9311 (Fig. 3 and Table 1, which is
published as supporting information on the PNAS web site).
Organic Nitrogen and Other Transporters. CC9311 and WH8102
also differ in other aspects of their membrane transporter
exposed to in their different environments. Interestingly,
CC9311 has multiple AMT family ammonia transporters and
based on this, ammonia is arguably its most important nitrogen
source, but determining this will require in situ gene expression
studies. CC9311 encodes a TRAP family dicarboxylate trans-
porter as well as a DASS family transporter that may also be
specific for carboxylates and a formate?nitrite transporter that is
not present in WH8102. CC9311 also encodes a second type of
predicted urea transporter and two APC-type amino acid trans-
porters that are not present in WH8102. These capabilities are
consistent with the coastal isolate CC9311 being exposed to
more organic matter than its oligotrophic ocean relative
WH8102. There is a significant expansion of mechanosensitive
ion channels in CC9311, which has five MscS and two MscL
members compared with only two MScS channels in WH8102.
Mechanosensitive ion channels can function as ‘‘emergency
structure. The outer scale designates coordinates in base pairs. The first circle
shows predicted coding regions on the plus strand, color coded by role
categories: violet, amino acid biosynthesis; light blue, biosynthesis of cofac-
tors, prosthetic groups, and carriers; light green, cell envelope; red, cellular
light gray, energy metabolism; magenta, fatty acid, and phospholipid metab-
olism; pink, protein synthesis and fate; orange, purines, pyrimidines, nucleo-
sides, and nucleotides; olive, regulatory functions and signal transduction;
dark green, transcription; teal, transport, and binding proteins; gray, un-
known function; salmon, other categories; and blue, hypothetical proteins.
The second circle shows predicted coding regions on the minus strand color
coded by role categories. The third circle shows in red the set of 1,730 genes
conserved between Synechococcus CC9311 and WH8102, the fourth circle
shows percentage G?C in relation to the mean G?C in a 2,000-bp window in
black, and the fifth circle shows the trinucleotide composition in black.
www.pnas.org?cgi?doi?10.1073?pnas.0602963103Palenik et al.
relief valves’’ during conditions of osmotic shock, implying that
the coastal isolate CC9311 may be subject to a more osmotically
challenging environment (30).
Light and CC9311. The predicted ORFs associated with photosyn-
thesis and light harvesting are relatively similar to WH8102. One
exception is the much greater number of high light-inducible
protein (HLIP) gene family members in CC9311 (with 14)
compared to WH8102 (with eight). Increased HLIP content has
been associated with cyanobacteria found in high light environ-
ments (16), thus these results predict that CC9311 would have
the capacity to live in high light surface waters or under changing
light conditions found during mixing of the water column.
Some differences in the ORFs clustered in the phycobilisome-
encoding region were found between WH8102 and CC9311, and
these may play a role in the type IV chromatic light adaptation
discovered in CC9311 (12). The genome sequence identifies two
ORFs (sync?0485 and sync?0486) as phycobiliprotein lyases not
found in WH8102; such proteins were predicted to be involved
in chromatic adaptation in a recent biochemical study (31).
These ORFs clearly merit further attention.
Horizontal Gene Transfer. Strains WH8102 and CC9311 share
1,730 ORFs. Mapping these on the CC9311 genome indicated
they were unevenly distributed, with a number of intervening
regions that essentially lacked any genes conserved with
WH8102 (Fig. 1). Analysis of these regions indicated that some
(?116 ORFs with 19 regions of ?3 kb) displayed an atypical
trinucleotide composition and GC percentage, suggesting they
may be novel genomic ‘‘islands’’ relatively recently acquired by
CC9311 (Table 2, which is published as supporting information
(15) had also identified putative similar islands based on their
atypical nucleotide content. These WH8102 putative islands also
essentially lacked any of the 1,730 conserved Synechococcus
The putative genomic islands with atypical nucleotide content
of gene function. The majority of the WH8102 islands consist
largely of hypothetical genes, often flanked by phage integrase
genes, suggesting they may be of phage origin. In contrast, none
of the CC9311 islands contain phage integrase genes or other
identifiable phage genes. It has been hypothesized that lysogenic
phages would be more common in nutrient-poor environments
such as the open ocean (discussed in ref. 32). The residual
phage-related genes in open ocean WH8102 but not CC9311 are
some of the first data consistent with this hypothesis.
Both genomes have unique islands consisting of different
polysaccharide biosynthesis genes that may be important in
changing cell surface characteristics, perhaps in response to
phage or grazing selection pressure. Other islands unique to
CC9311 encode an ABC secretion system and an RTX family
toxin homologue, a predicted secreted nuclease and protease,
and some two-component regulatory system genes. Some of the
MED4 (PMMxxxx), and SS120 (Proxxxx). This maximum-likelihood phylogenetic tree was generated by using PHYLIP, and bootstrap values are indicated next to
the branch nodes. Orthologous clusters conserved in all of the cyanobacteria shown are highlighted by lines on the side, the phosphate sensor is labeled, and
the divergent sensors unique to CC9311 are highlighted with asterisks.
Phylogenetic tree of sensor kinases from Synechococcus CC9311 (sync?xxxx), and WH8102 (SYNWxxxx), Prochlorococcus marinus MI9313 (PMTxxxx),
Palenik et al. PNAS ?
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previously mentioned metal metabolism genes, including a fer-
ritin and ferrous iron transport genes, are also found in these
islands. The presence of metal-related (especially iron) genes in
these islands with atypical codon usage is interesting, because it
suggests that metal usage may also be under strong selection.
Genes with new physiological capabilities for metal use may be
highly favored and maintained in CC9311, if acquired through
horizontal gene transfer.
Cell Surfaces: LPS and Pili. CC9311 (relative to WH8102) is missing
the genes for the synthesis of KDO, a molecule necessary for the
biosynthesis of a typical LPS, and is missing genes for one
pathway for the biosynthesis of the sugar rhamnose, a potential
component of LPS. The genes for the synthesis of lipid A, the
lipid part of LPS, were found. At its simplest level, this suggests
that CC9311 has differences in its LPS compared to WH8102.
Preliminary LPS analyses suggest this to be the case (B.P., B.
Brahamsha, P. Azadi, and S. Snyder, unpublished work). A
greatly altered LPS could drastically change the sensitivity of
CC9311 to particular phages; because of its abundance at the cell
surface, LPS is often a phage receptor (33).
Thus it may have pili that would be available for twitching
motility or DNA uptake. Both of these could be potentially
useful in coastal ecosystems where CC9311 is more likely to
encounter surfaces or DNA than in the open ocean. In contrast,
CC9311 is missing two major cell surface proteins (SwmA and
SwmB) involved in swimming motility in WH8102 (34, 35). The
use of the CC9311 genome and other nonmotile Synechococcus
genomes will help determine genes unique to WH8102 and thus
other genes that could be involved in its unique form of
swimming motility. However, our examination of these WH8102
‘‘unique’’ genes so far has not yielded clues, because many of
these genes are annotated only as hypothetical or conserved
Summary. The coastal strain CC9311 has dramatic differences in
gene complement compared to the open ocean strain WH8102.
Many of these differences are consistent with adaptation to a
coastal environment. Because the genus marine Synechococcus
contains multiple clades (potential species), it will be interesting
to see which of these coastal?open ocean differences will be
conserved across all clades or whether, even within coastal
clades, different strategies exist for adapting to this complex
Genome Sequencing, Annotation, and Characteristics. The complete
genome sequence of Synechococcus CC9311 was determined by
indicating the direction of transport. Metal-binding proteins and metalloenzymes are shown inside the cell, and the number of copies of each system is shown
in parentheses or within the protein. The color shading of the proteins indicates their distribution: magenta, present in both WH8102 and CC9311; red, present
only in CC9311; and blue, present only in WH8102. Hatching indicates that the gene is located in a region with atypical trinucleotide content.
www.pnas.org?cgi?doi?10.1073?pnas.0602963103Palenik et al.
using the whole-genome shotgun method (36). Physical and Download full-text
sequencing gaps were closed by using a combination of primer
walking, generation and sequencing of transposon-tagged librar-
ies of large-insert clones, and multiplex PCR (37). Identification
of putative protein-encoding genes and annotation of the ge-
nome were performed as described (38). An initial set of ORFs
predicted to encode proteins was initially identified by using
GLIMMER (39). ORFs consisting of ?30 codons and those
containing overlaps were eliminated. Frame shifts and point
mutations were corrected or designated ‘‘authentic.’’ Functional
assignment, identification of membrane-spanning domains, and
determination of paralogous gene families were performed as
generated by using the methods described (38). The CC9311
genome was found to be composed of one circular chromosome
of 2,606,748 bp (Fig. 1), with an average GC content of 52.5%.
A total of 3,065 ORFs, 2 rRNA operons, and 44 tRNAs were
identified within the CC9311 genome.
Trinucleotide Composition. Distribution of all 64 trinucleotides (3
mers) was determined, and the 3-mer distribution in 2,000-bp
windows that overlapped by half their length (1,000 bp) across
the genome was computed. For each window, we computed the
?2statistic on the difference between its 3-mer content and that
of the whole chromosome. A large value for ?2indicates the
chromosome. Probability values for this analysis are based on
assumptions that the DNA composition is relatively uniform
throughout the genome, and that 3-mer composition is indepen-
dent. Because these assumptions may be incorrect, we prefer to
interpret high ?2values as indicators of regions on the chromo-
some that appear unusual and demand further scrutiny.
Comparative Genomics. The Synechococcus CC9311 and WH8102
genomes were compared at the nucleotide level by suffix tree
analysis by using MUMmer (40), and their ORFs were compared
by a reciprocal best BLAST match analysis by using an E-value
cutoff of 10?5.
We thank The Institute for Genomic Research faculty, sequencing
facility, and informatics group for expert advice and assistance. This
work was supported by National Science Foundation Grant EF0333162.
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