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Comparative Genomic Analysis of Integral Membrane Transport Proteins in Ciliates

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Comparative Genomic Analysis of Integral Membrane Transport Proteins in Ciliates UC San Diego UC San Diego Previously Published Works Title Comparative genomic analysis of integral membrane transport proteins in ciliates. Permalink https://escholarship.org/uc/item/3g98s19z Journal The Journal of eukaryotic microbiology, 62(2) ISSN 1066-5234 Authors Kumar, Ujjwal Saier, Milton H Publication Date 2015-03-01 DOI 10.1111/jeu.12156 Peer reviewed eScholarship.org Powered by the California Digital Library University of California The Journal of Published by the International Society of Eukaryotic Microbiology Protistologists Journal of Eukaryotic Microbiology ISSN 1066-5234 ORIGINAL ARTICLE Comparative Genomic Analysis of Integral Membrane Transport Proteins in Ciliates Ujjwal Kumar & Milton H. Saier Jr Division of Biological Sciences, University of California at San Diego, La Jolla, California Keywords ABSTRACT Channels; evolution; genome analyses; secondary carriers. Integral membrane transport proteins homologous to those found in the Transporter Classification Database (TCDB; www.tcdb.org) were identified and Correspondence bioinformatically characterized by transporter class, family, and substrate speci- M. H. Saier Jr, Division of Biological ficity in three ciliates, Paramecium tetraurelia (Para), Tetrahymena thermophila Sciences, University of California at San (Tetra), and Ichthyophthirius multifiliis (Ich). In these three organisms, 1,326 of Diego, La Jolla, CA 92093-0116, USA 39,600 proteins (3.4%), 1,017 of 24,800 proteins (4.2%), and 504 out of 8,100 Telephone number: +858-534-4084; proteins (6.2%) integral membrane transport proteins were identified, respec- FAX number: +858-534-7108; tively. Thus, an inverse relationship was observed between the % transporters e-mail: [email protected] identified and the number of total proteins per genome reported. This surpris- ing observation provides insight into the evolutionary process, giving rise to Received: 5 December 2013; revised 23 genome reduction following whole genome duplication (as in the case of Para) April 2014; accepted April 28, 2014. or during pathogenic association with a host organism (Ich). Of these transport proteins in Para and Tetra, about 41% were channels (more than any other doi:10.1111/jeu.12156 type of organism studied), 31% were secondary carriers (fewer than most eukaryotes) and 26% were primary active transporters, mostly ATP-hydrolysis driven (more than most other eukaryotes). In Ich, the number of channels was selectively reduced by 66%, relative to Para and Tetra. Para has four times more inorganic anion transporters than Tetra, and Ich has nonselectively lost most of these. Tetra and Ich preferentially transport sugars and monocarboxy- lates while Para prefers di- and tricarboxylates. These observations serve to characterize the transport proteins of these related ciliates, providing insight into their nutrition and metabolism. CILIATES are unicellular eukaryotes named for the hair-like important discoveries in disciplines ranging from basic cellu- cilia that cover their bodies. They are found in many aqua- lar and molecular processes to complex genomics (Bracht tic environments ranging from coastal waters to hydro- et al. 2013; Coyne et al. 2012). Although unicellular, they thermal vents. They play important ecological roles in their share many of the same genes as multicellular organisms, environments by preying on smaller microorganisms such and they have many large and complex organelles that can as bacteria, algae, yeast, and other ciliates, providing food be targeted for study (Beisson et al. 2010a,b). for invertebrates, fish larvae and protozoans, thus allowing All ciliates have two nuclei, a large somatic nucleus, the nutrient transfer to larger organisms (Dopheide et al. macronucleus, wherein the genes are expressed, and a 2009). The nearly 5,000 known ciliate species comprise a small silent germline nucleus, the micronucleus, which is major portion of the planet’s plankton (Caron et al. 2012). used exclusively in reproduction (Prescott 1994). Their ma- These organisms have adopted a range of life styles cronuclei can be restructured, fragmented, scrambled, including heterotrophic, photosynthetic, aerobic, anaerobic, rejoined, degraded, rebuilt and amplified in various ways, free living, symbiotic, and parasitic (Coyne et al. 2011; mediated in part by transposons that are controlled epige- Ricard et al. 2008). netically (Nowacki et al. 2008, 2010; Swart et al. 2013; Yao Ciliates, such as Tetrahymena thermophila (Tetra) and et al. 2003). Lastly, Both Tetra and Para are easy to cul- Paramecium tetraurelia (Para) in particular, are important ture and have rapid rates of reproduction (Cassidy-Hanley model organisms that have been used to make numerous 2012). © 2014 The Author(s) Journal of Eukaryotic Microbiology © 2014 International Society of Protistologists Journal of Eukaryotic Microbiology 2015, 62, 167–187 167 Ciliate Transporters Kumar & Saier Ichthyophthirius multifiliis (Ich) is a parasitic ciliate that sequences of T. thermophila strain SB210, P. tetraurelia is closely related to Tetra (Alvarez-Pellitero 2008). Ich’s strain d4-2 and I. multifiliis strain d were used (Aury et al. parasitic lifestyle has resulted in a greatly reduced genome 2006; Coyne et al. 2011; Eisen et al. 2006). Each as compared to Tetra. Ich parasitizes a wide range of fish, sequence in the proteomes was used as a query and causing White Spot Disease (Dickerson and Clark 1998). It blasted against TCDB using the program, G-BLAST (Reddy invades the epidermis of fish and eventually grows to and Saier 2012). such a large size that it can be seen by the naked eye as G-BLAST is a tool to screen all proteins encoded within a white spot on the surface of the infected fish. Infection a genome against all protein entries in TCDB. The program of the gills can result in the death of the fish by asphyxia- retrieves information for both the query and top hit tion (Coyne et al. 2011). Ich does not need an intermedi- sequences, TC#, protein size in number of amino acyl resi- ate host to reproduce, but it is not known if it can dues, number of transmembrane segments (TMSs), e- reproduce sexually. Ich outbreaks have resulted in exten- value for the query and hit proteins, regions of sequence sive economic loss in both aquaculture and the ornamen- similarity and regions of TMS overlap. The low complexity tal fish industry (Ling et al. 2012). Prevention of these filter was not used as it is normally of value only for larger outbreaks becomes increasingly important as we look to datasets including proteins with multiple repeat elements. fish farming to feed our burgeoning human population In addition, each open reading frame was scanned with (Picon-Camacho et al. 2012). the HMMTOP 2.0 program to predict the number of puta- Transport proteins, comprising 5–10% of an organism’s tive TMSs. The Web-based Hydropathy, Amphipathicity, genome, are essential for cell homeostasis and survival and Topology (WHAT) program (Tusnady and Simon 2001; (Paulsen et al. 2001). They provide vital cellular processes Zhai and Saier 2001) was used with a window size of 19 such as uptake of nutrients, export of wastes, and signal residues and an angle of 100° (as is appropriate for alpha transduction (Lam et al. 2011). A comparative genome helices) to display the hydropathy plot for individual pro- analysis of the transporters found within Tetra, Para, and teins in order to resolve the differences in the numbers of Ich should help elucidate key aspects of their lifestyles TMSs between the proteins retrieved and their TCDB ho- and physiology (Barabote et al. 2007; Lorca et al. 2007; mologs. The plot generated by WHAT allows the user to Youm and Saier 2012). judge if a program such as HMMTOP has missed a TMS Para is not as closely related to the other two ciliates or has predicted a TMS inappropriately. A cut-off value of and has undergone at least two (possibly three) whole 0.001 was used with the G-BLAST program to eliminate genome duplication events (Aury et al. 2006; Prescott false positives and proteins with unreliable degrees of 1994; Sogin and Silberman 1998), probably one more sequence divergence. duplication than observed for Tetra or Ich (Eisen et al. Proteins with no predicted TMSs were eliminated so 2006). Tetra and Para shared their last common ancestor that only integral membrane proteins, primarily multispan- after the first genome duplication event. Although Tetra ning membrane proteins, were retrieved. Proteins with and Ich are much more closely related, their stark differ- only an N-terminal signal sequence are numerous because ences in lifestyle have produced two very different these proteins include almost all secreted proteins that genomes. By seeing what transporters were lost, retained are exported via the Sec translocase. The topological pre- or expanded, we can gain important insight into the meta- diction programs often miss these TMSs, recording the bolic requirements, means of pathogenicity (in Ich), and proteins to have zero TMSs. Consequently, the numbers adaptability to different environments. of 0 or 1 TMS proteins retrieved were not reliable and In this paper, we analyze the genomes of Para, Tetra, were therefore not always recorded. and Ich for all integral membrane transport proteins that The G-BLAST algorithm, set up with the parameters correspond to currently recognized transporters included described above, is able to recognize all transporter pro- within the Transporter Classification Database (TCDB; tein homologs that are sufficiently similar in sequence to www.tcdb.org; Saier et al. 2006, 2009, 2014; Youm and any sequence in TCDB to give a score of less than (smal- Saier 2012). These systems fall into several classes includ- ler than) 0.001. Every such sequence retrieved was con- ing (1) channels/pores, (2) secondary carriers, (3) primary firmed. It should be noted that transport proteins of active transporters, (4) group translocators, (5) transmem- functions that have not yet been identified may also have brane electron flow carriers, (8) auxiliary transport pro- been excluded from our study, but their identification will teins, and (9) transporters of unknown mechanism of only be possible when such proteins are identified.
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