Cheong Xin Chan

Publications

• 29.75

  Impact points

  Cyanophora paradoxa genome elucidates origin of photosynthesis in algae and plants.

  Dana C Price, Cheong Xin Chan, Hwan Su Yoon, Eun Chan Yang, Huan Qiu, Andreas P M Weber, Rainer Schwacke, Jeferson Gross, Nicolas A Blouin, Chris Lane, [......], Maria Cecilia Arias, Bernard Henrissat, Pedro M Coutinho, Stefan A Rensing, Aikaterini Symeonidi, Harshavardhan Doddapaneni, Beverley R Green, Veeran D Rajah, Jeffrey Boore, Debashish Bhattacharya

  Science (New York, N.Y.). 02/2012; 335(6070):843-7.

  The primary endosymbiotic origin of the plastid in eukaryotes more than 1 billion years ago led to the evolution of algae and plants. We analyzed draft genome and transcriptome data from the basally diverging alga Cyanophora paradoxa and provide evidence for a single origin of the primary plastid in... [more] The primary endosymbiotic origin of the plastid in eukaryotes more than 1 billion years ago led to the evolution of algae and plants. We analyzed draft genome and transcriptome data from the basally diverging alga Cyanophora paradoxa and provide evidence for a single origin of the primary plastid in the eukaryote supergroup Plantae. C. paradoxa retains ancestral features of starch biosynthesis, fermentation, and plastid protein translocation common to plants and algae but lacks typical eukaryotic light-harvesting complex proteins. Traces of an ancient link to parasites such as Chlamydiae were found in the genomes of C. paradoxa and other Plantae. Apparently, Chlamydia-like bacteria donated genes that allow export of photosynthate from the plastid and its polymerization into storage polysaccharide in the cytosol.
• 6.24

  Impact points

  Analysis of Porphyra Membrane Transporters Demonstrates Gene Transfer among Photosynthetic Eukaryotes and Numerous Sodium-Coupled Transport Systems.

  Cheong Xin Chan, Simone Zäuner, Glen Wheeler, Arthur R Grossman, Simon E Prochnik, Nicolas A Blouin, Yunyun Zhuang, Christoph Benning, Gry Mine Berg, Charles Yarish, Renée L Eriksen, Anita S Klein, Senjie Lin, Ira Levine, Susan H Brawley, Debashish Bhattacharya

  Plant physiology. 02/2012; 158(4):2001-12.

  Membrane transporters play a central role in many cellular processes that rely on the movement of ions and organic molecules between the environment and the cell, and between cellular compartments. Transporters have been well characterized in plants and green algae, but little is known about transpo... [more] Membrane transporters play a central role in many cellular processes that rely on the movement of ions and organic molecules between the environment and the cell, and between cellular compartments. Transporters have been well characterized in plants and green algae, but little is known about transporters or their evolutionary histories in the red algae. Here we examined 482 expressed sequence tag contigs that encode putative membrane transporters in the economically important red seaweed Porphyra (Bangiophyceae, Rhodophyta). These contigs are part of a comprehensive transcriptome dataset from Porphyra umbilicalis and Porphyra purpurea. Using phylogenomics, we identified 30 trees that support the expected monophyly of red and green algae/plants (i.e. the Plantae hypothesis) and 19 expressed sequence tag contigs that show evidence of endosymbiotic/horizontal gene transfer involving stramenopiles. The majority (77%) of analyzed contigs encode transporters with unresolved phylogenies, demonstrating the difficulty in resolving the evolutionary history of genes. We observed molecular features of many sodium-coupled transport systems in marine algae, and the potential for coregulation of Porphyra transporter genes that are associated with fatty acid biosynthesis and intracellular lipid trafficking. Although both the tissue-specific and subcellular locations of the encoded proteins require further investigation, our study provides red algal gene candidates associated with transport functions and novel insights into the biology and evolution of these transporters.
• 3.94

  Impact points

  Lateral transfer of genes and gene fragments in Staphylococcus extends beyond mobile elements.

  Cheong Xin Chan, Robert G Beiko, Mark A Ragan

  Journal of bacteriology. 05/2011; 193(15):3964-77.

  The widespread presence of antibiotic resistance and virulence among Staphylococcus isolates has been attributed in part to lateral genetic transfer (LGT), but little is known about the broader extent of LGT within this genus. Here we report the first systematic study of the modularity of genetic tr... [more] The widespread presence of antibiotic resistance and virulence among Staphylococcus isolates has been attributed in part to lateral genetic transfer (LGT), but little is known about the broader extent of LGT within this genus. Here we report the first systematic study of the modularity of genetic transfer among 13 Staphylococcus genomes covering four distinct named species. Using a topology-based phylogenetic approach, we found, among 1,354 sets of homologous genes examined, strong evidence of LGT in 368 (27.1%) gene sets, and weaker evidence in another 259 (19.1%). Within-gene and whole-gene transfer contribute almost equally to the topological discordance of these gene sets against a reference phylogeny. Comparing genetic transfer in single-copy and in multicopy gene sets, we observed a higher frequency of LGT in the latter, and a substantial functional bias in cases of whole-gene transfer (little such bias was observed in cases of fragmentary genetic transfer). We found evidence that lateral transfer, particularly of entire genes, impacts not only functions related to antibiotic, drug, and heavy-metal resistance, as well as membrane transport, but also core informational and metabolic functions not associated with mobile elements. Although patterns of sequence similarity support the cohesion of recognized species, LGT within S. aureus appears frequently to disrupt clonal complexes. Our results demonstrate that LGT and gene duplication play important parts in functional innovation in staphylococcal genomes.

• Non-random sharing of Plantae genes.

  Cheong Xin Chan, Debashish Bhattacharya

  Communicative & integrative biology. 05/2011; 4(3):361-3.

  The power of eukaryote genomics relies strongly on taxon sampling. This point was underlined in a recent analysis of red algal genome evolution in which we tested the Plantae hypothesis that posits the monophyly of red, green (including plants) and glaucophyte algae. The inclusion of novel genome da... [more] The power of eukaryote genomics relies strongly on taxon sampling. This point was underlined in a recent analysis of red algal genome evolution in which we tested the Plantae hypothesis that posits the monophyly of red, green (including plants) and glaucophyte algae. The inclusion of novel genome data from two mesophilic red algae enabled us to robustly demonstrate the sisterhood of red and green algae in the tree of life. Perhaps more exciting was the finding that >1,800 putative genes in the unicellular red alga Porphyridium cruentum showed evidence of gene-sharing with diverse lineages of eukaryotes and prokaryotes. Here we assessed the correlation between the putative functions of these shared genes and their susceptibility to transfer. It turns out that genes involved in complex interactive networks such as biological regulation and transcription/translation are less susceptible to endosymbiotic or horizontal gene transfer, when compared to genes with metabolic and transporter functions.
• 6.24

  Impact points

  Plastid origin and evolution: new models provide insights into old problems.

  Cheong Xin Chan, Jeferson Gross, Hwan Su Yoon, Debashish Bhattacharya

  Plant physiology. 02/2011; 155(4):1552-60.

  Algae are defined by their photosynthetic organelles (plastids) that have had multiple independent origins in different phyla. These instances of organelle transfer significantly complicate inference of the tree of life for eukaryotes because the intracellular gene transfer (endosymbiotic gene trans... [more] Algae are defined by their photosynthetic organelles (plastids) that have had multiple independent origins in different phyla. These instances of organelle transfer significantly complicate inference of the tree of life for eukaryotes because the intracellular gene transfer (endosymbiotic gene transfer, EGT) associated with each round of endosymbiosis generates highly chimeric algal nuclear genomes. In this Update we review the current state in the field of endosymbiosis research with a focus on the use of the photosynthetic amoeba Paulinella to advance our knowledge of plastid evolution and current ideas about the origin of the plastid translocons. These research areas have been revolutionized by the advent of modern genomic approaches.
• 10.99

  Impact points

  Red and green algal monophyly and extensive gene sharing found in a rich repertoire of red algal genes.

  Cheong Xin Chan, Eun Chan Yang, Titas Banerjee, Hwan Su Yoon, Patrick T Martone, José M Estevez, Debashish Bhattacharya

  Current biology : CB. 02/2011; 21(4):328-33.

  The Plantae comprising red, green (including land plants), and glaucophyte algae are postulated to have a single common ancestor that is the founding lineage of photosynthetic eukaryotes. However, recent multiprotein phylogenies provide little or no support for this hypothesis. This may reflect limi... [more] The Plantae comprising red, green (including land plants), and glaucophyte algae are postulated to have a single common ancestor that is the founding lineage of photosynthetic eukaryotes. However, recent multiprotein phylogenies provide little or no support for this hypothesis. This may reflect limited complete genome data available for red algae, currently only the highly reduced genome of Cyanidioschyzon merolae, a reticulate gene ancestry, or variable gene divergence rates that mislead phylogenetic inference. Here, using novel genome data from the mesophilic Porphyridium cruentum and Calliarthron tuberculosum, we analyze 60,000 novel red algal genes to test the monophyly of red + green (RG) algae and their extent of gene sharing with other lineages. Using a gene-by-gene approach, we find an emerging signal of RG monophyly (supported by ∼50% of the examined protein phylogenies) that increases with the number of distinct phyla and terminal taxa in the analysis. A total of 1,808 phylogenies show evidence of gene sharing between Plantae and other lineages. We demonstrate that a rich mesophilic red algal gene repertoire is crucial for testing controversial issues in eukaryote evolution and for understanding the complex patterns of gene inheritance in protists.

• Plastid origin and evolution

  Cheong Xin Chan, Debashish Bhattacharya

  Encyclopedia of Life Sciences (eLS). 01/2011; http://www.els.net/:doi:10.1002/9780470015902.a002363.

  Plastids (or chloroplasts in plants) are organelles within which photosynthesis takes place in eukaryotes. The origin of the widespread plastid traces back to a cyanobacterium that was engulfed and retained by a heterotrophic protist through a process termed primary endosymbiosis. Subsequent (serial... [more] Plastids (or chloroplasts in plants) are organelles within which photosynthesis takes place in eukaryotes. The origin of the widespread plastid traces back to a cyanobacterium that was engulfed and retained by a heterotrophic protist through a process termed primary endosymbiosis. Subsequent (serial) events of endosymbiosis, involving red and green algae and potentially other eukaryotes, yielded the so-called ‘complex’ plastids found in photosynthetic taxa such as diatoms, dinoflagellates and euglenids. The field of plastid research also includes nonphotosynthetic organelles (apicoplasts) within the parasitic apicomplexans and the temporary sequestration (‘theft’) of plastids by heterotrophic organisms (kleptoplasty) such as the sea slug Elysia chlorotica. The gain and loss of plastids, and nonlineal gene transfer (associated with endosymbiosis) are key aspects of algal evolution that have decisive impacts on inference of their phylogenetic positions in the tree of life. Deciphering plastid origin therefore provides general insights into the evolution of eukaryote lineages.
• 4.41

  Impact points

  Red and green algal origin of diatom membrane transporters: insights into environmental adaptation and cell evolution.

  Cheong Xin Chan, Adrian Reyes-Prieto, Debashish Bhattacharya

  PloS one. 01/2011; 6(12):e29138.

  Membrane transporters (MTs) facilitate the movement of molecules between cellular compartments. The evolutionary history of these key components of eukaryote genomes remains unclear. Many photosynthetic microbial eukaryotes (e.g., diatoms, haptophytes, and dinoflagellates) appear to have undergone s... [more] Membrane transporters (MTs) facilitate the movement of molecules between cellular compartments. The evolutionary history of these key components of eukaryote genomes remains unclear. Many photosynthetic microbial eukaryotes (e.g., diatoms, haptophytes, and dinoflagellates) appear to have undergone serial endosymbiosis and thereby recruited foreign genes through endosymbiotic/horizontal gene transfer (E/HGT). Here we used the diatoms Thalassiosira pseudonana and Phaeodactylum tricornutum as models to examine the evolutionary origin of MTs in this important group of marine primary producers. Using phylogenomics, we used 1,014 diatom MTs as query against a broadly sampled protein sequence database that includes novel genome data from the mesophilic red algae Porphyridium cruentum and Calliarthron tuberculosum, and the stramenopile Ectocarpus siliculosus. Our conservative approach resulted in 879 maximum likelihood trees of which 399 genes show a non-lineal history between diatoms and other eukaryotes and prokaryotes (at the bootstrap value ≥70%). Of the eukaryote-derived MTs, 172 (ca. 25% of 697 examined phylogenies) have members of both red/green algae as sister groups, with 103 putatively arising from green algae, 19 from red algae, and 50 have an unresolved affiliation to red and/or green algae. We used topology tests to analyze the most convincing cases of non-lineal gene history in which red and/or green algae were nested within stramenopiles. This analysis showed that ca. 6% of all trees (our most conservative estimate) support an algal origin of MTs in stramenopiles with the majority derived from green algae. Our findings demonstrate the complex evolutionary history of photosynthetic eukaryotes and indicate a reticulate origin of MT genes in diatoms. We postulate that the algal-derived MTs acquired via E/HGT provided diatoms and other related microbial eukaryotes the ability to persist under conditions of fluctuating ocean chemistry, likely contributing to their great success in marine environments.
• 4.41

  Impact points

  Are protein domains modules of lateral genetic transfer?

  Cheong Xin Chan, Aaron E Darling, Robert G Beiko, Mark A Ragan

  PLoS ONE. 02/2009; 4(2):e4524.

  BACKGROUND: In prokaryotes and some eukaryotes, genetic material can be transferred laterally among unrelated lineages and recombined into new host genomes, providing metabolic and physiological novelty. Although the process is usually framed in terms of gene sharing (e.g. lateral gene transfer, LGT... [more] BACKGROUND: In prokaryotes and some eukaryotes, genetic material can be transferred laterally among unrelated lineages and recombined into new host genomes, providing metabolic and physiological novelty. Although the process is usually framed in terms of gene sharing (e.g. lateral gene transfer, LGT), there is little reason to imagine that the units of transfer and recombination correspond to entire, intact genes. Proteins often consist of one or more spatially compact structural regions (domains) which may fold autonomously and which, singly or in combination, confer the protein's specific functions. As LGT is frequent in strongly selective environments and natural selection is based on function, we hypothesized that domains might also serve as modules of genetic transfer, i.e. that regions of DNA that are transferred and recombined between lineages might encode intact structural domains of proteins. METHODOLOGY/PRINCIPAL FINDINGS: We selected 1,462 orthologous gene sets representing 144 prokaryotic genomes, and applied a rigorous two-stage approach to identify recombination breakpoints within these sequences. Recombination breakpoints are very significantly over-represented in gene sets within which protein domain-encoding regions have been annotated. Within these gene sets, breakpoints significantly avoid the domain-encoding regions (domons), except where these regions constitute most of the sequence length. Recombination breakpoints that fall within longer domons are distributed uniformly at random, but those that fall within shorter domons may show a slight tendency to avoid the domon midpoint. As we find no evidence for differential selection against nucleotide substitutions following the recombination event, any bias against disruption of domains must be a consequence of the recombination event per se. CONCLUSIONS/SIGNIFICANCE: This is the first systematic study relating the units of LGT to structural features at the protein level. Many genes have been interrupted by recombination following inter-lineage genetic transfer, during which the regions within these genes that encode protein domains have not been preferentially preserved intact. Protein domains are units of function, but domons are not modules of transfer and recombination. Our results demonstrate that LGT can remodel even the most functionally conservative modules within genomes.

• Lateral transfer of genes and gene fragments in prokaryotes.

  Cheong Xin Chan, Robert G Beiko, Aaron E Darling, Mark A Ragan

  Genome biology and evolution. 01/2009; 1:429-38.

  Lateral genetic transfer (LGT) involves the movement of genetic material from one lineage into another and its subsequent incorporation into the new host genome via genetic recombination. Studies in individual taxa have indicated lateral origins for stretches of DNA of greatly varying length, from a... [more] Lateral genetic transfer (LGT) involves the movement of genetic material from one lineage into another and its subsequent incorporation into the new host genome via genetic recombination. Studies in individual taxa have indicated lateral origins for stretches of DNA of greatly varying length, from a few nucleotides to chromosome size. Here we analyze 1,462 sets of single-copy, putatively orthologous genes from 144 fully sequenced prokaryote genomes, asking to what extent complete genes and fragments of genes have been transferred and recombined in LGT. Using a rigorous phylogenetic approach, we find evidence for LGT in at least 476 (32.6%) of these 1,462 gene sets: 286 (19.6%) clearly show one or more "observable recombination breakpoints" within the boundaries of the open reading frame, while a further 190 (13.0%) yield trees that are topologically incongruent with the reference tree but do not contain a recombination breakpoint within the open reading frame. We refer to these gene sets as observable recombination breakpoint positive (ORB(+)) and negative (ORB(-)) respectively. The latter are prima facie instances of lateral transfer of an entire gene or beyond. We observe little functional bias between ORB(+) and ORB(-) gene sets, but find that incorporation of entire genes is potentially more frequent in pathogens than in nonpathogens. As ORB(+) gene sets are about 50% more common than ORB(-) sets in our data, the transfer of gene fragments has been relatively frequent, and the frequency of LGT may have been systematically underestimated in phylogenetic studies.

• A phylogenomic approach for studying plastid endosymbiosis.

  Ahmed Moustafa, Cheong Xin Chan, Megan Danforth, David Zear, Hiba Ahmed, Nagnath Jadhav, Trevor Savage, Debashish Bhattacharya

  Genome informatics. International Conference on Genome Informatics. 01/2008; 21:165-76.

  Gene transfer is a major contributing factor to functional innovation in genomes. Endosymbiotic gene transfer (EGT) is a specific instance of lateral gene transfer (LGT) in which genetic materials are acquired by the host genome from an endosymbiont that has been engulfed and retained in the cytopla... [more] Gene transfer is a major contributing factor to functional innovation in genomes. Endosymbiotic gene transfer (EGT) is a specific instance of lateral gene transfer (LGT) in which genetic materials are acquired by the host genome from an endosymbiont that has been engulfed and retained in the cytoplasm. Here we present a comprehensive approach for detecting gene transfer within a phylogenetic framework. We applied the approach to examine EGT of red algal genes into Thalassiosira pseudonana, a free-living diatom for which a complete genome sequence has recently been determined. Out of 11,390 predicted protein-coding sequences from the genome of T. pseudonana, 124 (1.1%, clustered into 80 gene families) are inferred to be of red algal origin (bootstrap support >or= 75%). Of these 80 gene families, 22 (27.5%) encode novel, unknown functions. We found 21.3% of the gene families to putatively encode non-plastid-targeted proteins. Our results suggest that EGT of red algal genes provides a relatively minor contribution to the nuclear genome of the diatom, but the transferred genes have functions that extend beyond photosynthesis. This assertion awaits experimental validation. Whereas the current study is focused within the context of secondary endosymbiosis, our approach can be applied to large-scale detection of gene transfer in any system.

• Genetic transfer in Staphylococcus: a case study of 13 genomes

  Cheong Xin Chan, Robert G Beiko, Mark A Ragan

  10/2007;

  The widespread presence of antibiotic resistance and virulence among Staphylococcus isolates has been attributed to lateral genetic transfer (LGT) between different strains or species. However, there has been very little study of the extent of LGT in Staphylococcus species using a phylogenetic appro... [more] The widespread presence of antibiotic resistance and virulence among Staphylococcus isolates has been attributed to lateral genetic transfer (LGT) between different strains or species. However, there has been very little study of the extent of LGT in Staphylococcus species using a phylogenetic approach, particularly of the units of such genetic transfer. Here we report the first systematic study of the units of genetic transfer in 13 Staphylococcus genomes, using a rigorous phylogenetic approach. We found clear evidence of LGT in 26.1% of the 1354 homologous gene families examined, and possibly more in another 17.9% of the total families. Within-gene and whole-gene transfer contribute almost equally to the discordance of these gene families against a reference phylogeny. Comparing genetic transfer in single-copy and in multi-copy gene families, we found little functional bias in cases of within-gene (fragmentary) genetic transfer but substantial functional bias in cases of whole-gene (non-fragmentary) genetic transfer, and we observed a higher frequency of LGT in multi-copy gene families. Our results demonstrate that LGT and gene duplication play an important part among the factors that contribute to functional innovation in staphylococcal genomes.

• Units of genetic transfer in prokaryotes

  Cheong Xin Chan, Robert G Beiko, Mark A Ragan

  10/2007;

  The transfer of genetic materials across species (lateral genetic transfer, LGT) contributes to genomic and physiological innovation in prokaryotes. The extent of LGT in prokaryotes has been examined in a number of studies, but the unit of transfer has not been studied in a rigorous manner. Using a ... [more] The transfer of genetic materials across species (lateral genetic transfer, LGT) contributes to genomic and physiological innovation in prokaryotes. The extent of LGT in prokaryotes has been examined in a number of studies, but the unit of transfer has not been studied in a rigorous manner. Using a rigorous phylogenetic approach, we analysed the units of LGT within families of single-copy genes obtained from 144 fully sequenced prokaryote genomes. A total of 30.3% of these gene families show evidence of LGT. We found that the transfer of gene fragments has been more frequent than the transfer of entire genes, suggesting the extent of LGT has been underestimated. We found little functional bias between within-gene (fragmentary) and whole-gene (non-fragmentary) genetic transfer, but non-fragmentary transfer has been more frequent into pathogens than into non-pathogens. As gene families that contain probable paralogs were excluded from the current study, our results may still underestimate the extent of LGT; nonetheless this is the most-comprehensive study to date of the unit of LGT among prokaryote genomes.

• Protein domains as units of genetic transfer

  Cheong Xin Chan, Robert G Beiko, Aaron E Darling, Mark A Ragan

  10/2007;

  Genomes evolve as modules. In prokaryotes (and some eukaryotes), genetic material can be transferred between species and integrated into the genome via homologous or illegitimate recombination. There is little reason to imagine that the units of transfer correspond to entire genes; however, such uni... [more] Genomes evolve as modules. In prokaryotes (and some eukaryotes), genetic material can be transferred between species and integrated into the genome via homologous or illegitimate recombination. There is little reason to imagine that the units of transfer correspond to entire genes; however, such units have not been rigorously characterized. We examined fragmentary genetic transfers in single-copy gene families from 144 prokaryotic genomes and found that breakpoints are located significantly closer to the boundaries of genomic regions that encode annotated structural domains of proteins than expected by chance, particularly when recombining sequences are more divergent. This correlation results from recombination events themselves and not from differential nucleotide substitution. We report the first systematic study relating genetic recombination to structural features at the protein level.

• A two-phase approach for detecting recombination in nucleotide sequences

  Cheong Xin Chan, Robert G Beiko, Mark A Ragan

  10/2007;

  Genetic recombination can produce heterogeneous phylogenetic histories within a set of homologous genes. Delineating recombination events is important in the study of molecular evolution, as inference of such events provides a clearer picture of the phylogenetic relationships among different gene se... [more] Genetic recombination can produce heterogeneous phylogenetic histories within a set of homologous genes. Delineating recombination events is important in the study of molecular evolution, as inference of such events provides a clearer picture of the phylogenetic relationships among different gene sequences or genomes. Nevertheless, detecting recombination events can be a daunting task, as the performance of different recombinationdetecting approaches can vary, depending on evolutionary events that take place after recombination. We recently evaluated the effects of postrecombination events on the prediction accuracy of recombination-detecting approaches using simulated nucleotide sequence data. The main conclusion, supported by other studies, is that one should not depend on a single method when searching for recombination events. In this paper, we introduce a two-phase strategy, applying three statistical measures to detect the occurrence of recombination events, and a Bayesian phylogenetic approach in delineating breakpoints of such events in nucleotide sequences. We evaluate the performance of these approaches using simulated data, and demonstrate the applicability of this strategy to empirical data. The two-phase strategy proves to be time-efficient when applied to large datasets, and yields high-confidence results.
• 9.88

  Impact points

  Trends in seaweed research.

  Cheong Xin Chan, Chai-Ling Ho, Siew-Moi Phang

  Trends in plant science. 05/2006; 11(4):165-6.
• 3.43

  Impact points

  Detecting recombination in evolving nucleotide sequences.

  Cheong Xin Chan, Robert G Beiko, Mark A Ragan

  BMC bioinformatics. 02/2006; 7:412.

  BACKGROUND: Genetic recombination can produce heterogeneous phylogenetic histories within a set of homologous genes. These recombination events can be obscured by subsequent residue substitutions, which consequently complicate their detection. While there are many algorithms for the identification o... [more] BACKGROUND: Genetic recombination can produce heterogeneous phylogenetic histories within a set of homologous genes. These recombination events can be obscured by subsequent residue substitutions, which consequently complicate their detection. While there are many algorithms for the identification of recombination events, little is known about the effects of subsequent substitutions on the accuracy of available recombination-detection approaches. RESULTS: We assessed the effect of subsequent substitutions on the detection of simulated recombination events within sets of four nucleotide sequences under a homogeneous evolutionary model. The amount of subsequent substitutions per site, prior evolutionary history of the sequences, and reciprocality or non-reciprocality of the recombination event all affected the accuracy of the recombination-detecting programs examined. Bayesian phylogenetic-based approaches showed high accuracy in detecting evidence of recombination event and in identifying recombination breakpoints. These approaches were less sensitive to parameter settings than other methods we tested, making them easier to apply to various data sets in a consistent manner. CONCLUSION: Post-recombination substitutions tend to diminish the predictive accuracy of recombination-detecting programs. The best method for detecting recombined regions is not necessarily the most accurate in identifying recombination breakpoints. For difficult detection problems involving highly divergent sequences or large data sets, different types of approach can be run in succession to increase efficiency, and can potentially yield better predictive accuracy than any single method used in isolation.
• 4.93

  Impact points

  A word-oriented approach to alignment validation.

  Robert G Beiko, Cheong Xin Chan, Mark A Ragan

  Bioinformatics (Oxford, England). 06/2005; 21(10):2230-9.

  MOTIVATION: Multiple sequence alignment at the level of whole proteomes requires a high degree of automation, precluding the use of traditional validation methods such as manual curation. Since evolutionary models are too general to describe the history of each residue in a protein family, there is ... [more] MOTIVATION: Multiple sequence alignment at the level of whole proteomes requires a high degree of automation, precluding the use of traditional validation methods such as manual curation. Since evolutionary models are too general to describe the history of each residue in a protein family, there is no single algorithm/model combination that can yield a biologically or evolutionarily optimal alignment. We propose a 'shotgun' strategy where many different algorithms are used to align the same family, and the best of these alignments is then chosen with a reliable objective function. We present WOOF, a novel 'word-oriented' objective function that relies on the identification and scoring of conserved amino acid patterns (words) between pairs of sequences. RESULTS: Tests on a subset of reference protein alignments from BAliBASE showed that WOOF tended to rank the (manually curated) reference alignment highest among 1060 alternative (automatically generated) alignments for a majority of protein families. Among the automated alignments, there was a strong positive relationship between the WOOF score and similarity to the reference alignment. The speed of WOOF and its independence from explicit considerations of three-dimensional structure make it an excellent tool for analyzing large numbers of protein families. AVAILABILITY: On request from the authors.

• Units Of Genetic Transfer In Prokaryotes

  Cheong Xin Chan

  The transfer of genetic material and integration of the material into a genome via recombination are important in gene repair, maintenance of genetic variation, and initiation of DNA replication in prokaryotes. Lateral transfer of genetic materials between two species creates mosaic phylogenetic rel... [more] The transfer of genetic material and integration of the material into a genome via recombination are important in gene repair, maintenance of genetic variation, and initiation of DNA replication in prokaryotes. Lateral transfer of genetic materials between two species creates mosaic phylogenetic relationships in different regions across genomes, complicating the inference of a single species phylogeny based on gene sequences. To date, most studies of genetic transfer in prokaryotes have been restricted by the implicit assumption that the units of genetic transfer are whole genes. This thesis documents the implementation of a rigorous phylogenetic approach in the first systematic study of the unit of genetic transfer in prokaryotes. Two core aspects of the thesis are reviewed in detail: (a) the modelling of sequence changes in the study of molecular evolution, and (b) the detection of recombination (thus genetic transfer) in molecular sequences. A ‘shotgun’ strategy is adopted to obtain optimal sequence alignments for subsequent analysis of genetic transfer, in which multiple alignments resulting from various algorithms were validated using a novel pattern-centric objective function presented in this work. A two-phase strategy is introduced to detect recombination at large scale: simple statistical tests are used to detect phylogenetic discrepancies within a group of sequences, and a rigorous Bayesian phylogenetic approach is then used to locate more precisely the breakpoints at which the recombination occurred. To formulate this strategy, an extensive benchmark study on various recombination-detecting approaches was conducted using simulated sequence data, focusing on the effects of subsequent evolutionary events in obscuring recombination. The alignment and recombination-detection strategies were applied to analyse the units of genetic transfer in (a) single-copy gene families from 144 prokaryote genomes and in (b) single-copy and multicopy gene families from 13 Staphylococcus genomes. In prokaryotes, within-gene (fragmentary) genetic transfer is generally more frequent than whole-gene transfer in singlecopy gene families. In Staphylococcus, however, both within-gene and whole-gene transfer contribute almost evenly. The units of fragmentary genetic transfer are found to correlate with protein structural features. A significant functional bias of whole-gene transfer was observed in single-copy and in multi-copy gene families of Staphylococcus, suggesting that fixation of an exogenous gene is influenced by the presence of similar gene copies in the target genome. This work demonstrates that units of genetic transfer in prokaryotes are not restricted to whole genes, and the extent of genetic transfer in prokaryotes could have been underestimated. The results support the view that both genetic transfer and gene duplication contribute to functional innovation in prokaryote genomes.

• Large-scale detection of recombination in nucleotide sequences

  Cheong Xin Chan, Robert G Beiko, Mark A Ragan

  Genetic recombination following a genetic transfer event can produce heterogeneous phylogenctic histories within sets of genes that share a common ancestral origin. Delineating recombination events will enhance our understanding in genome evolution. However, the task of detecting recombination is no... [more] Genetic recombination following a genetic transfer event can produce heterogeneous phylogenctic histories within sets of genes that share a common ancestral origin. Delineating recombination events will enhance our understanding in genome evolution. However, the task of detecting recombination is not trivial due to effect of more-recent evolutionary changes that can obscure such event from detection. In this paper, we demonstrate the use of a two-phase strategy for detecting recombination events on a large-scale dataset.