Phylogenetic detection of numerous gene duplications shared by animals, fungi and plants
© Zhou et al.; licensee BioMed Central Ltd. 2010
Received: 1 December 2009
Accepted: 6 April 2010
Published: 6 April 2010
Gene duplication is considered a major driving force for evolution of genetic novelty, thereby facilitating functional divergence and organismal diversity, including the process of speciation. Animals, fungi and plants are major eukaryotic kingdoms and the divergences between them are some of the most significant evolutionary events. Although gene duplications in each lineage have been studied extensively in various contexts, the extent of gene duplication prior to the split of plants and animals/fungi is not clear.
Here, we have studied gene duplications in early eukaryotes by phylogenetic relative dating. We have reconstructed gene families (with one or more orthogroups) with members from both animals/fungi and plants by using two different clustering strategies. Extensive phylogenetic analyses of the gene families show that, among nearly 2,600 orthogroups identified, at least 300 of them still retain duplication that occurred before the divergence of the three kingdoms. We further found evidence that such duplications were also detected in some highly divergent protists, suggesting that these duplication events occurred in the ancestors of most major extant eukaryotic groups.
Our phylogenetic analyses show that numerous gene duplications happened at the early stage of eukaryotic evolution, probably before the separation of known major eukaryotic lineages. We discuss the implication of our results in the contexts of different models of eukaryotic phylogeny. One possible explanation for the large number of gene duplication events is one or more large-scale duplications, possibly whole genome or segmental duplication(s), which provides a genomic basis for the successful radiation of early eukaryotes.
The history of eukaryotic evolution is one of ever-increasing diversity and complexity at multiple levels. The increases in genotypic and phenotypic complexity are usually associated with expansion of gene families. For instance, it has been shown that the diversification of gene families involved in cell differentiation and cell-cell communication contributed to the origination of multicellularity . Other well-known examples are the MADS-box genes in plants  and olfactory receptor genes in animals . These multigene families are subject to birth-and-death evolution and most new genes arise by gene duplication .
Gene duplication has been a ubiquitous phenomenon during eukaryotic history and has contributed to evolutionary innovation by generating additional genetic material for functional divergence and novelty . After gene duplication, one of the duplicates might be released from selective pressure and have the potential to evolve new functions ('neofunctionalization') . Alternatively, the two duplicates can accumulate different degenerative mutations and each retains a subset of the ancestral functions ('subfunctionalization') . In addition, in certain situations, such subfunctionalization can lead to the optimization of subdivided ancestral functions in each duplicate, thus contributing to adaptation . Besides its important role in the evolution of new gene functions, gene duplication also greatly contributes to the speciation process through the divergent resolution of duplicated genes in different populations . Large-scale gene duplication events have been documented in animals and fungi, and are particularly frequent in plants [8–14] and are believed to be associated with dramatic increases in species diversity, such as the radiation of vertebrates and the diversification of flowering plants [15, 16].
Previous phylogenetic studies of individual eukaryotic gene families for transcription regulators, kinesins, and recombinational proteins all indicate that there were duplication events before the split of animals and plants, suggestive of abundant gene duplication during early eukaryotic evolution [30–35]. This notion is also supported by a comparative genomic study, in which the established COG (prokaryotic clusters of orthologous groups) and KOG (eukaryotic clusters of orthologous groups) databases were used to reconstruct gene clusters and to analyze their phylogenies . It was found that the inferred number of genes in the last eukaryotic common ancestor is 1.92-fold higher than in the first eukaryotic common ancestor, leading to the conclusion that early eukaryotes had significantly more gene duplication than prokaryotes during similar periods . However, a systematic investigation of the extent of gene duplication prior to the split of plants and animals/fungi is still lacking. Here, we present extensive phylogenetic analyses of gene families and our results supporting the hypothesis that many of these families had experienced at least one duplication event before the divergence of the three major eukaryotic kingdoms.
Reconstruction of gene clusters with the Markov Clustering Algorithm method
To identify gene duplication in early eukaryotic evolution, we reconstructed gene families from representative eukaryotic and prokaryotic species. The three multicellular eukaryotic kingdoms, plants, animals and fungi, belong to two of the six major eukaryotic supergroups (plants in Archaeplastida; animals and fungi both in Opisthokonta) . According to the 'six supergroups' model of eukaryotic phylogeny (Figure 1b) and other recent phylogenies, the separation of plants and animals/fungi could have been as early as the separation of any major groups of extant eukaryotes. Hence, gene duplications prior to the split of plants and animals/fungi can be placed at an early stage of eukaryotic evolution.
In this study, we included three representatives of Archaeplastida (the flowering plant Arabidopsis thaliana, the moss Physcomitrella patens and the green alga Chlamydomonas reinhardtii), three animals (Homo sapiens, the pufferfish Takifugu rubripes and the sea urchin Strongylocentrotus purpuratus) and two fungi (the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe), which all have nearly complete genome sequences (Table S1 in Additional file 1). According to a widely accepted model for the eukaryotic origin, the ancestral eukaryotic cell was derived from an Archaea-like organism, with additional genes originated from the endosymbiosis of a proteobacterium-like cell, which evolved into the mitochondrion . Therefore, we included genes from three bacteria (Escherichia coli, Rickettsia prowazekii and Bacillus subtilis) and three archaea (Methanosarcina acetivorans, Sulfolobus solfataricus and Pyrobaculum aerophilum) as outgroups (Table S1 in Additional file 1).
The predicted protein sequences from all these 14 species were clustered using the Markov Clustering Algorithm (MCL; see Methods), which is among the most popular clustering methods and has been shown to be reliable . By using a relatively low clustering stringency, 222,436 annotated protein sequences from the 14 representative species were divided into 51,396 gene clusters in total. Among these, 1,394 clusters contained both prokaryotic and eukaryotic genes and 41,444 clusters were eukaryote-specific. In addition, 794 out of the 1,394 clusters and 2,276 out of the 41,444 clusters contained genes from both Archaeplastida and Opisthokonta. The numbers of clusters of other phyletic patterns are summarized in Table S2 in Additional file 1.
Analysis I - MCL clusters with both prokaryotic and eukaryotic genes
Number of orthogroups and early eukaryotic duplications identified in analysis I
Type I orthogroup with duplication
Type I orthogroup total
Type II orthogroup with duplication
Type II orthogroup total
Total orthogroup with duplication
We reasoned that some of the gene duplications identified might be caused by long-branch attraction (LBA) artifacts in phylogenetic reconstruction. For example, in an orthogroup with the phyletic pattern of ((plants, animals, fission yeast) (budding yeast)), it was possible that the fission yeast gene evolved rapidly and was placed at the basal position due to LBA. In this case, a duplication event would be inferred based on the incorrect topology. Therefore, to minimize the impact of LBA, we used a more stringent criterion for the identification of gene duplication before the divergence of plants and animals/fungi: at least one gene from at least one species must be present in each of two paralogous clades. Based on this conservative criterion, we still found about 25% (BS ≥ 50%) or 15% (BS ≥ 70%) of the orthogroups to have experienced an early eukaryotic duplication (Table 1, entries in bold). Also, the ML-aLRT test showed that more than 30% of orthogroups (at support levels of both 50% and 70%) have experienced an early eukaryotic duplication (Table 1, entries in bold). This stringent criterion was also used in analyses II and III (see below). Moreover, we arbitrarily selected a subset of the orthogroups with topologies that were vulnerable to LBA, and added sequences from additional species to further test the impact of LBA. The results showed that phylogenies of most of the orthogroups tested (15 out of 21) still supported early eukaryotic duplication (Table S4 in Additional file 1). Especially, all six orthogroups that initially showed duplication at a support level of 70% still supported early eukaryotic duplication after adding more sequences. These results suggest that our phylogenetic topologies are quite reliable.
Distribution of orthogroups with phyletic patterns supporting early eukaryotic duplication
Analysis II - MCL clusters with eukaryotic genes only
Number of orthogroups and early eukaryotic duplications identified in analysis II
Number of orthogroups with duplication
Percentage out of 1,903 clusters
Analysis III - reanalysis of the KOG-to-COG clusters
To further strengthen our investigation of ancient eukaryotic gene duplication, we wanted to test an independent dataset of gene clusters to evaluate the reliability of the results. We used an existing dataset of gene clusters with both eukaryotic and prokaryotic members that was established with a different methodology from that of our analysis I ; this is our analysis III. In their study, Makarova et al.  used established databases  of prokaryotic clusters of orthologous groups (COGs) and their eukaryotic counterparts (KOGs) to construct KOG-to-COG clusters. A COG was defined by best hits from BLAST analyses with members from at least three relatively distant prokaryotes among a total of 63 species included in the study . Similarly, a KOG contains best hits from at least three eukaryotic species from a group of seven in the earlier study ; the total number of eukaryotes was increased to 11 subsequently . The authors used RPS-BLAST search to find the best COG hit for each KOG and all the KOGs that have the same COG best-hit were assigned to one cluster . In total, they identified 1,092 KOG-to-COG clusters (each with one COG), which covered 2,445 KOGs  (Additional file 2).
Number of orthogroups and early eukaryotic duplications identified in analysis III
Type I orthogroup with duplication
Type I orthogroup total
Type II orthogroup with duplication
Type II orthogroup total
Total orthogroup with duplication
Comparison of gene copy number between human and Arabidopsis
Detection of very ancient eukaryotic gene duplications
In this study, we investigated the extent of eukaryotic gene duplication before the divergence of plants and animals/fungi by constructing gene clusters with members from representative prokaryotic and eukaryotic species and performing comprehensive phylogenetic analyses.
As we sampled only a small number of species from each lineage, additional cluster analyses were performed by adding genes from zebrafish (teleost fish), medaka (teleost fish), Drosophila melanogaster (insect) or the giant clam Lottia gigantean (mollusc), respectively (see Additional file 3 for complete clustering results). We found that adding genes from each of the additional species resulted in very slight changes in gene cluster numbers (Table S7 in Additional file 1). Therefore, we believe that our overall results would not be dramatically affected by inclusion of the additional animal species.
Our analysis I was based on the gene clusters delineated by the MCL method, and revealed that about 25% (BS ≥ 50%) or 15% (BS ≥ 70%) of orthogroups had experienced ancient gene duplication. Higher numbers and percentages of orthogroups that showed ancient gene duplication were reported by the ML-aLRT test (also in analyses II and III), possibly because the bootstrap test is consistently conservative . It is known that, in comparative genomics studies like the ones we performed here, the accuracy of gene family clustering has a great impact on the reliability of subsequent analyses such as phylogenetic reconstruction. Therefore, it is of interest to check whether alternative strategies of gene family clustering would lead to similar results as the MCL approach used in analysis I. COG and its eukaryotic equivalent, KOG, are among the most widely used databases of orthologous gene clusters. In our analysis III, we took the KOG-to-COG clusters identified by Makarova et al.  and analyzed them using the same procedures as used in analysis I. In comparison to analysis I, in analysis III we obtained a very similar percentage of orthogroups showing early eukaryotic duplication, although the total number of orthogroups identified was higher. Interestingly, however, we found that less than half of the orthogroups with duplication overlap between the two analyses. The differences were mainly due to two reasons: first, the prokaryotic members in a particular MCL cluster were not in any COG or the corresponding COG were not in any KOG-to-COG cluster; second, a KOG-to-COG cluster may include sequences of very limited similarity, resulting in a phylogeny different from that of the corresponding MCL cluster. Nonetheless, the fact that different gene family clustering methods (MCL and COG/KOG) and phylogenetic approaches (NJ and ML) all revealed similar percentages of orthogroups that had experienced early eukaryotic duplication still supports the reliability of our results.
One possible bias in our analysis I is that only the eukaryotic genes with detectable prokaryotic homologs were studied. This means that we focused on relatively conserved genes. In consideration of the antiquity of the gene duplication events we are interested in, some eukaryotic genes might lack detectable homologs in the prokaryotes in our study due to gene loss or sequence divergence and thus were not included in our analysis I. For this reason, we also carried out analysis II to analyze the eukaryote-specific MCL gene clusters and found that more than 10% of the 1,903 gene clusters showed early eukaryotic duplication. It is possible that this figure is still an underestimation since some of the ancient duplicates might fail to be clustered together due to a high degree of divergence and would appear as separate gene clusters without early eukaryotic duplication.
Our phylogenetic analyses identified approximately 300 (BS support ≥ 70%) or approximately 500 (aLRT support ≥ 70%) gene duplications in the time window from the origin of eukaryotes to the plants-animals/fungi split. However, the estimation of the length of this time window varies depending on which eukaryotic phylogeny is adopted. According to the 'crown-stem' model of eukaryotic phylogeny (Figure 1a), plants and animals/fungi are members of a crown group and several groups of protists form deep branches in the tree [18, 19]. It was estimated that plants and animals/fungi separated approximately 1,600 million years ago (MYA), and Giardia, which was considered the deepest branch in the eukaryotic tree of life, diverged approximately 2,300 MYA . Given the estimated origin of eukaryotes at approximately 2,700 MYA , the duplication events identified in our study could have taken place during the long time period before the separation of plants and animals/fungi (approximately 1,100 million years). A contrasting picture is depicted by the more recent 'six supergroups' classification of eukaryotes (Figure 1b) [21–23].
In this model and other related models, both the 'unikont-bikont' topology [26, 27] and the recent 'photosynthetic-nonphotosynthetic' bipartition  suggest that the Archaeplastida-Opisthokonta separation might represent the first major split, or at least one of the early splits, in eukaryotic evolution (Figure 1b). In this perspective, the duplication events we identified could be placed during a very early stage of eukaryotic evolution, prior to the divergence of most of the major extant protist groups.
Regardless of whether the 'crown-stem' model, or 'six supergroups' and other similar models are correct, we investigated gene duplications among a wider representation of eukaryotes using phylogenetic analyses with additional sequences from exemplars of divergent major protist groups, Excavata, Amoebozoa, and Chromalveolata (Figure 1b). For most of the gene families with 70% BS support, the duplication likely occurred prior to the separation of these highly divergent protists from plants and/or animals/fungi. Even according to the 'crown-stem' model of early eukaryotic history, these divergent protists separated from plants/animals/fungi at an earlier time. Therefore, irrespective of the models of early eukaryotic phylogeny, these duplications would be placed before any known major eukaryotic divergence. Therefore, our results support many gene duplication events during very early eukaryotic evolution.
Functional implication for early eukaryotic evolution
The gene duplications we detected likely generated raw materials for functional evolution, as proposed before . Indeed, the duplicates from the 300 or more gene duplications we identified would most likely be eliminated if they did not provide selective advantage. Therefore, these early eukaryotic gene duplications could have been of great importance for the success and radiation of early eukaryotes, and thus have been retained in the last common ancestor of extant major eukaryotic groups. If the duplicated gene families are involved in processes that are fundamental to early eukaryotes, which are likely to be also shared by extant eukaryotes, they might show similar evolutionary patterns in different eukaryotic kingdoms. Specifically, copy numbers for genes with highly conserved functions seem to be more stable than the number of genes with more divergent functions (compare RAD51, MSH, and SMC with JmjC and MADS-box genes) [30, 31, 33–35].
In fact, we observed a more positive correlation of gene family size between animals and plants in the families with early eukaryotic duplication than in the families without such duplication (Figure 4). In other words, the families with the early eukaryotic duplication tend to have more similar evolutionary patterns in both plants and animals/fungi than those families without the early duplication, suggesting that these genes might have relatively conserved functions among the three major kingdoms. This idea of functional conservation is also supported by the finding that the (RO)(RO) pattern, in which both duplicates are retained in both the plants and animal/fungi lineages, is the most frequent pattern among all possible patterns.
Also, it is of interest to know whether genes with specific biochemical or molecular functions or involved in specific processes are enriched among the families with duplication. Interestingly, our Gene Ontology (GO) analysis did not reveal any GO terms significantly enriched among the orthogroups with duplication (data not shown). This might suggest that the detected gene duplications, which we propose could have benefited the early eukaryotic ancestor and the ancestors of both the plant and animal/fungi lineages, affected many types of functions and processes, not just a few specialized classes of functions.
A hypothesis for early eukaryotic large-scale duplication
Gene duplication can be generated by several mechanisms, including tandem duplication, transposition and large-scale duplication (for example, segmental/whole genome duplication (WGD)). In principle, the 300 or more gene duplications we identified could be independent events resulting from tandem duplication and transposition. However, in the absence of supporting evidence, such a complex pattern of multiple independent events is not parsimonious. Alternatively, the duplications could be explained by one or a few large-scale duplications. Large-scale duplication, like WGD, is of special interest because it allows the generation of multiple new functional modules with many genes that are unrelated at the sequence level , which would not be likely by other duplication mechanisms. Also, segmental duplications (SDs) are increasingly recognized as frequent phenomena, especially in primate genomes - for example, approximately 5% of the human genome consists of duplicated segments . Therefore, SDs with sufficiently large numbers of genes could also account for the gene duplications we detected. After WGD/SDs, the different fates of duplicated genes in different populations could generate the genetic diversity that then allows both reproductive isolation/speciation and environmental adaptation [47, 48].
The large number of ancient eukaryotic duplication events that we have detected here could have been the result of one or more early eukaryotic large-scale duplications. For relatively recent large-scale duplication events, it is possible to identify syntenic genomic regions . For example, such syntenic regions were found for the most recent WGD in Arabidopsis, poplar and yeast, which likely occurred approximately 100 MYA or more recently [10–12, 50]. However, for older ones such as the WGDs in vertebrate (1R/2R; approximately 525 to 875 MYA ), synteny is no longer detectable due to numerous genome rearrangements and gene loss . If a large-scale duplication was the cause of the ancient gene duplication events identified in this study, this event would have occurred at least 1,600 MYA (possibly even earlier), making it exceedingly unlikely that any synteny can still be detected. Another approach to the detection of large-scale duplication is to analyze the rate of synonymous base substitutions (dS) between paralogous genes, as reported for many plant species [53, 54]. Unfortunately, this method is also not feasible for events older than approximately 150 million years because of the saturation of dS values.
An alternative way to obtain evidence for large-scale duplication is to examine the phylogeny of a large number of gene families, as we have done here. Our results indicate that a significant fraction of the orthogroups in our dataset had experienced duplication before the divergence of the three major eukaryotic kingdoms. By combining the results of analyses I and II, we estimated that the percentage of orthogroups showing duplication before the separation of plants and animals/fungi is over 15% (BS ≥ 50% support level) and 10% (BS ≥ 70% support level), or about 30% (aLRT support ≥ 50%) and 20% (aLRT support ≥ 70%). Similar large-scale phylogenetic analyses showed that, among the duplicate pairs resulting from more recent WGD in vertebrates (1R/2R; approximately 525 to 875 MYA) and yeast (approximately 100 MYA), 26.6% and 20.1% of the pairs survived, respectively [51, 55]. The early eukaryotic duplications we studied were much more ancient than the previously reported large-scale duplications in animals, plants and yeast. Thus, during the at least 1,600 million years of evolution, the duplicate pairs that arose in early eukaryotes might have had a higher chance to be lost or to be too divergent to be recognized. Therefore, it is reasonable to expect that a lower percentage of the duplicate pairs would survive, and our phylogenetic results could support the hypothesis that the duplication events identified here are the remnants of a large-scale duplication (for example, WGD or SDs) in early eukaryotes. In other words, considering the antiquity of the early eukaryotic duplications, the 300 or more duplications we detected probably represent only a small fraction of the real number of duplications in early eukaryotes, which could be in the thousands. Our results could be most parsimoniously interpreted by one or more large-scale duplications, which were likely to be WGD/SDs, rather than thousands of independent duplications.
In this study, we conducted extensive phylogenetic analyses to investigate the extent of gene duplication in early eukaryotic evolution. We have found at least 300 orthogroups that had likely experienced an ancient eukaryotic duplication event prior to the divergence of the major eukaryotic supergroups. Our results provide a better understanding of early eukaryotic evolution in several ways. The identification of numerous ancient eukaryotic gene duplication events suggests that gene duplication played an important role in the evolution of early eukaryotes. The large number of duplicated genes might have allowed large-scale evolution of new gene functions, increasing the chance of greater species diversity in changing environments. In particular, the shared duplications in plants and animals/fungi might have contributed to the three independent origins of multicellularity in these lineages. Furthermore, these ancient duplications could be most simply explained by a hypothesized early eukaryotic WGD/SDs. We further postulate that this/these WGD/SDs might have contributed to the early eukaryotic radiation. Therefore, like the early vertebrate and angiosperm diversifications, the hypothesized WGD/SDs could provide an explanation at the level of genome evolution for the high rate of speciation near the origin of the three major eukaryotic lineages.
Materials and methods
Reconstruction of gene clusters
For analyses I and II, the predicted protein sequences of the 14 representative species were retrieved from public databases (see Table S1 in Additional file 1 for the complete list of data sources). These protein sequences were compared using an all-to-all BLASTP search with a cut-off of 1e-10 . Based on the BLASTP results, MCL clustering was performed with low stringency (inflation value of 1.5) to produce gene clusters . To check the clusters for common domains, the domain architectures of all cluster members were annotated using InterProScan v4.5 (InterPro release 22.0, including both integrated and un-integrated) .
For analysis III, we started from the 1,092 KOG-to-COG clusters identified in the study of Makarova et al. . Since the original KOG database does not cover the genomes of Physcomitrella, Chlamydomonas, Takifugu and Strongylocentrotus, the predicted protein sequences from these four species were assigned to KOGs using BLASTP search. Then the sequences from the 14 representative prokaryotic and eukaryotic species were extracted from each KOG-to-COG cluster to form the dataset for the following phylogenetic analysis.
For all the MCL gene clusters and KOG-to-COG clusters, highly similar sequences (more than 80% identity) from the same species were removed by using BLASTCLUST . Multiple sequence alignments were generated by using MUSCLE 3.6 . The multiple sequence alignments were trimmed by removing poorly aligned regions using trimAl 1.2 with the automated1 option . NJ trees were constructed using PHYLIP 3.68 (JTT model) with 1,000 bootstrap replicates [60, 61]. ML trees were constructed using RAxML 7.2.0 (LG model plus gamma correction) with 100 bootstrap replicates [62, 63]. The best-scoring ML trees were also evaluated with the aLRT method by using Phyml 3.0 [64, 65]. For large clusters with more than 100 sequences, representative sequences were selected based on a preliminary NJ tree. Phylogenetic trees were screened by custom scripts to identify orthogroups and duplication events. All scripts in this study, gene clusters and phylogenetic trees are available upon request.
Gene Ontology analysis
Orthogroups with early eukaryotic duplication were compared with orthogroups that did not have such duplications for overrepresented GO terms . Domains encoded by the majority of orthogroup members were considered representatives for the orthogroup. Then GO annotations of representative InterPro domains were assigned to each orthogroup using InterPro2GO mapping . Subsequently, all GO annotations were mapped to GO slims, a cut-down version of GO, using the map2slim perl script and generic GO slim version 1.2 . The overrepresentation of GO slims was examined using Ontologizer 2.0  with term-for-term analysis and Bonferroni correction for multiple testing.
approximate likelihood ratio test
prokaryotic clusters of orthologous groups
eukaryotic clusters of orthologous groups
Markov Clustering Algorithm
million years ago
whole genome duplication.
We thank Professors Bryan Grenfell, Edward Holmes, Hongzhi Kong, Stephen Schaeffer, and anonymous reviewers for helpful comments. We thank Yuannian Jiao and Professor Claude dePamphilis for discussion on phylogenetic methods. This work was supported by a grant from the US Department of Energy (DE-FG02-02ER15332), the Biology Department, the Eberly College of Sciences, and the Huck Institutes of the Life Sciences, the Pennsylvania State University. XZ was supported in part by NSF Plant Genome Research Program (DEB 0638595, The Ancestral Angiosperm Genome Project). HM was also supported by funds from Fudan University.
- Rokas A: The origins of multicellularity and the early history of the genetic toolkit for animal development. Annu Rev Genet. 2008, 42: 235-251. 10.1146/annurev.genet.42.110807.091513.PubMedView ArticleGoogle Scholar
- Nam J, Kim J, Lee S, An G, Ma H, Nei M: Type I MADS-box genes have experienced faster birth-and-death evolution than type II MADS-box genes in angiosperms. Proc Natl Acad Sci USA. 2004, 101: 1910-1915. 10.1073/pnas.0308430100.PubMedPubMed CentralView ArticleGoogle Scholar
- Nei M, Rooney AP: Concerted and birth-and-death evolution of multigene families. Annu Rev Genet. 2005, 39: 121-152. 10.1146/annurev.genet.39.073003.112240.PubMedPubMed CentralView ArticleGoogle Scholar
- Ohno S: Evolution by Gene Duplication. 1970, Berlin-Heidelberg-NY: Springer-VerlagView ArticleGoogle Scholar
- Force A, Lynch M, Pickett FB, Amores A, Yan YL, Postlethwait J: Preservation of duplicate genes by complementary, degenerative mutations. Genetics. 1999, 151: 1531-1545.PubMedPubMed CentralGoogle Scholar
- Hittinger CT, Carroll SB: Gene duplication and the adaptive evolution of a classic genetic switch. Nature. 2007, 449: 677-681. 10.1038/nature06151.PubMedView ArticleGoogle Scholar
- Lynch M, Conery JS: The evolutionary fate and consequences of duplicate genes. Science. 2000, 290: 1151-1155. 10.1126/science.290.5494.1151.PubMedView ArticleGoogle Scholar
- Dehal P, Boore JL: Two rounds of whole genome duplication in the ancestral vertebrate. PLoS Biol. 2005, 3: e314-10.1371/journal.pbio.0030314.PubMedPubMed CentralView ArticleGoogle Scholar
- Jaillon O, Aury JM, Brunet F, Petit JL, Stange-Thomann N, Mauceli E, Bouneau L, Fischer C, Ozouf-Costaz C, Bernot A, Nicaud S, Jaffe D, Fisher S, Lutfalla G, Dossat C, Segurens B, Dasilva C, Salanoubat M, Levy M, Boudet N, Castellano S, Anthouard V, Jubin C, Castelli V, Katinka M, Vacherie B, Biemont C, Skalli Z, Cattolico L, Poulain J, et al: Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype. Nature. 2004, 431: 946-957. 10.1038/nature03025.PubMedView ArticleGoogle Scholar
- Wolfe KH, Shields DC: Molecular evidence for an ancient duplication of the entire yeast genome. Nature. 1997, 387: 708-713. 10.1038/42711.PubMedView ArticleGoogle Scholar
- Kellis M, Birren BW, Lander ES: Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae. Nature. 2004, 428: 617-624. 10.1038/nature02424.PubMedView ArticleGoogle Scholar
- Bowers JE, Chapman BA, Rong J, Paterson AH: Unravelling angiosperm genome evolution by phylogenetic analysis of chromosomal duplication events. Nature. 2003, 422: 433-438. 10.1038/nature01521.PubMedView ArticleGoogle Scholar
- Tang H, Wang X, Bowers JE, Ming R, Alam M, Paterson AH: Unraveling ancient hexaploidy through multiply-aligned angiosperm gene maps. Genome Res. 2008, 18: 1944-1954. 10.1101/gr.080978.108.PubMedPubMed CentralView ArticleGoogle Scholar
- Aury JM, Jaillon O, Duret L, Noel B, Jubin C, Porcel BM, Segurens B, Daubin V, Anthouard V, Aiach N, Arnaiz O, Billaut A, Beisson J, Blanc I, Bouhouche K, Camara F, Duharcourt S, Guigo R, Gogendeau D, Katinka M, Keller AM, Kissmehl R, Klotz C, Koll F, Le Mouel A, Lepere G, Malinsky S, Nowacki M, Nowak JK, Plattner H, et al: Global trends of whole-genome duplications revealed by the ciliate Paramecium tetraurelia. Nature. 2006, 444: 171-178. 10.1038/nature05230.PubMedView ArticleGoogle Scholar
- Taylor JS, Peer Van de Y, Meyer A: Genome duplication, divergent resolution and speciation. Trends Genet. 2001, 17: 299-301. 10.1016/S0168-9525(01)02318-6.PubMedView ArticleGoogle Scholar
- De Bodt S, Maere S, Peer Van de Y: Genome duplication and the origin of angiosperms. Trends Ecol Evol. 2005, 20: 591-597. 10.1016/j.tree.2005.07.008.PubMedView ArticleGoogle Scholar
- Koonin EV: The Biological Big Bang model for the major transitions in evolution. Biol Direct. 2007, 2: 21-10.1186/1745-6150-2-21.PubMedPubMed CentralView ArticleGoogle Scholar
- Sogin ML: Early evolution and the origin of eukaryotes. Curr Opin Genet Dev. 1991, 1: 457-463. 10.1016/S0959-437X(05)80192-3.PubMedView ArticleGoogle Scholar
- Sogin ML, Hinkle G, Leipe DD: Universal tree of life. Nature. 1993, 362: 795-10.1038/362795a0.PubMedView ArticleGoogle Scholar
- Sogin ML, Silberman JD: Evolution of the protists and protistan parasites from the perspective of molecular systematics. Int J Parasitol. 1998, 28: 11-20. 10.1016/S0020-7519(97)00181-1.PubMedView ArticleGoogle Scholar
- Adl SM, Simpson AG, Farmer MA, Andersen RA, Anderson OR, Barta JR, Bowser SS, Brugerolle G, Fensome RA, Fredericq S, James TY, Karpov S, Kugrens P, Krug J, Lane CE, Lewis LA, Lodge J, Lynn DH, Mann DG, McCourt RM, Mendoza L, Moestrup O, Mozley-Standridge SE, Nerad TA, Shearer CA, Smirnov AV, Spiegel FW, Taylor MF: The new higher level classification of eukaryotes with emphasis on the taxonomy of protists. J Eukaryot Microbiol. 2005, 52: 399-451. 10.1111/j.1550-7408.2005.00053.x.PubMedView ArticleGoogle Scholar
- Keeling PJ, Burger G, Durnford DG, Lang BF, Lee RW, Pearlman RE, Roger AJ, Gray MW: The tree of eukaryotes. Trends Ecol Evol. 2005, 20: 670-676. 10.1016/j.tree.2005.09.005.PubMedView ArticleGoogle Scholar
- Simpson AG, Roger AJ: The real 'kingdoms' of eukaryotes. Curr Biol. 2004, 14: R693-696. 10.1016/j.cub.2004.08.038.PubMedView ArticleGoogle Scholar
- Hampl V, Hug L, Leigh JW, Dacks JB, Lang BF, Simpson AG, Roger AJ: Phylogenomic analyses support the monophyly of Excavata and resolve relationships among eukaryotic "supergroups". Proc Natl Acad Sci USA. 2009, 106: 3859-3864. 10.1073/pnas.0807880106.PubMedPubMed CentralView ArticleGoogle Scholar
- Burki F, Shalchian-Tabrizi K, Pawlowski J: Phylogenomics reveals a new 'megagroup' including most photosynthetic eukaryotes. Biol Lett. 2008, 4: 366-369. 10.1098/rsbl.2008.0224.PubMedPubMed CentralView ArticleGoogle Scholar
- Stechmann A, Cavalier-Smith T: Rooting the eukaryote tree by using a derived gene fusion. Science. 2002, 297: 89-91. 10.1126/science.1071196.PubMedView ArticleGoogle Scholar
- Richards TA, Cavalier-Smith T: Myosin domain evolution and the primary divergence of eukaryotes. Nature. 2005, 436: 1113-1118. 10.1038/nature03949.PubMedView ArticleGoogle Scholar
- Arisue N, Hasegawa M, Hashimoto T: Root of the Eukaryota tree as inferred from combined maximum likelihood analyses of multiple molecular sequence data. Mol Biol Evol. 2005, 22: 409-420. 10.1093/molbev/msi023.PubMedView ArticleGoogle Scholar
- Rogozin IB, Basu MK, Csuros M, Koonin EV: Analysis of rare genomic changes does not support the unikont-bikont phylogeny and suggests cyanobacterial symbiosis as the point of primary radiation of eukaryotes. Genome Biol Evol. 2009, 2009: 99-113. 10.1093/gbe/evp011.Google Scholar
- Alvarez-Buylla ER, Pelaz S, Liljegren SJ, Gold SE, Burgeff C, Ditta GS, Ribas de Pouplana L, Martinez-Castilla L, Yanofsky MF: An ancestral MADS-box gene duplication occurred before the divergence of plants and animals. Proc Natl Acad Sci USA. 2000, 97: 5328-5333. 10.1073/pnas.97.10.5328.PubMedPubMed CentralView ArticleGoogle Scholar
- Zhou X, Ma H: Evolutionary history of histone demethylase families: distinct evolutionary patterns suggest functional divergence. BMC Evol Biol. 2008, 8: 294-10.1186/1471-2148-8-294.PubMedPubMed CentralView ArticleGoogle Scholar
- Miki H, Okada Y, Hirokawa N: Analysis of the kinesin superfamily: insights into structure and function. Trends Cell Biol. 2005, 15: 467-476. 10.1016/j.tcb.2005.07.006.PubMedView ArticleGoogle Scholar
- Lin Z, Kong H, Nei M, Ma H: Origins and evolution of the recA/RAD51 gene family: evidence for ancient gene duplication and endosymbiotic gene transfer. Proc Natl Acad Sci USA. 2006, 103: 10328-10333. 10.1073/pnas.0604232103.PubMedPubMed CentralView ArticleGoogle Scholar
- Lin Z, Nei M, Ma H: The origins and early evolution of DNA mismatch repair genes--multiple horizontal gene transfers and co-evolution. Nucleic Acids Res. 2007, 35: 7591-7603. 10.1093/nar/gkm921.PubMedPubMed CentralView ArticleGoogle Scholar
- Surcel A, Zhou X, Quan L, Ma H: Long-term maintenance of stable copy number in the eukaryotic SMC family: origin of a vertebrate meiotic SMC1 and fate of recent segmental duplicates. J Syst Evol. 2008, 46: 19-Google Scholar
- Makarova KS, Wolf YI, Mekhedov SL, Mirkin BG, Koonin EV: Ancestral paralogs and pseudoparalogs and their role in the emergence of the eukaryotic cell. Nucleic Acids Res. 2005, 33: 4626-4638. 10.1093/nar/gki775.PubMedPubMed CentralView ArticleGoogle Scholar
- Timmis JN, Ayliffe MA, Huang CY, Martin W: Endosymbiotic gene transfer: organelle genomes forge eukaryotic chromosomes. Nat Rev Genet. 2004, 5: 123-135. 10.1038/nrg1271.PubMedView ArticleGoogle Scholar
- Enright AJ, Van Dongen S, Ouzounis CA: An efficient algorithm for large-scale detection of protein families. Nucleic Acids Res. 2002, 30: 1575-1584. 10.1093/nar/30.7.1575.PubMedPubMed CentralView ArticleGoogle Scholar
- Tatusov RL, Fedorova ND, Jackson JD, Jacobs AR, Kiryutin B, Koonin EV, Krylov DM, Mazumder R, Mekhedov SL, Nikolskaya AN, Rao BS, Smirnov S, Sverdlov AV, Vasudevan S, Wolf YI, Yin JJ, Natale DA: The COG database: an updated version includes eukaryotes. BMC Bioinformatics. 2003, 4: 41-10.1186/1471-2105-4-41.PubMedPubMed CentralView ArticleGoogle Scholar
- Wang G, Kong H, Sun Y, Zhang X, Zhang W, Altman N, dePamphilis CW, Ma H: Genome-wide analysis of the cyclin family in Arabidopsis and comparative phylogenetic analysis of plant cyclin-like proteins. Plant Physiol. 2004, 135: 1084-1099. 10.1104/pp.104.040436.PubMedPubMed CentralView ArticleGoogle Scholar
- Xu G, Ma H, Nei M, Kong H: Evolution of F-box genes in plants: different modes of sequence divergence and their relationships with functional diversification. Proc Natl Acad Sci USA. 2009, 106: 835-840. 10.1073/pnas.0812043106.PubMedPubMed CentralView ArticleGoogle Scholar
- Hillis DM, Bull JJ: An empirical test of bootstrapping as a method for assessing confidence in phylogenetic analysis. Syst Biol. 1993, 42: 182-192.View ArticleGoogle Scholar
- Hedges SB, Blair JE, Venturi ML, Shoe JL: A molecular timescale of eukaryote evolution and the rise of complex multicellular life. BMC Evol Biol. 2004, 4: 2-10.1186/1471-2148-4-2.PubMedPubMed CentralView ArticleGoogle Scholar
- Blair Hedges S, Kumar S: Genomic clocks and evolutionary timescales. Trends Genet. 2003, 19: 200-206. 10.1016/S0168-9525(03)00053-2.PubMedView ArticleGoogle Scholar
- Freeling M, Thomas BC: Gene-balanced duplications, like tetraploidy, provide predictable drive to increase morphological complexity. Genome Res. 2006, 16: 805-814. 10.1101/gr.3681406.PubMedView ArticleGoogle Scholar
- Marques-Bonet T, Girirajan S, Eichler EE: The origins and impact of primate segmental duplications. Trends Genet. 2009, 25: 443-454. 10.1016/j.tig.2009.08.002.PubMedPubMed CentralView ArticleGoogle Scholar
- Semon M, Wolfe KH: Consequences of genome duplication. Curr Opin Genet Dev. 2007, 17: 505-512. 10.1016/j.gde.2007.09.007.PubMedView ArticleGoogle Scholar
- Koszul R, Fischer G: A prominent role for segmental duplications in modeling eukaryotic genomes. C R Biol. 2009, 332: 254-266. 10.1016/j.crvi.2008.07.005.PubMedView ArticleGoogle Scholar
- Peer Van de Y: Computational approaches to unveiling ancient genome duplications. Nat Rev Genet. 2004, 5: 752-763. 10.1038/nrg1449.PubMedView ArticleGoogle Scholar
- Tuskan GA, Difazio S, Jansson S, Bohlmann J, Grigoriev I, Hellsten U, Putnam N, Ralph S, Rombauts S, Salamov A, Schein J, Sterck L, Aerts A, Bhalerao RR, Bhalerao RP, Blaudez D, Boerjan W, Brun A, Brunner A, Busov V, Campbell M, Carlson J, Chalot M, Chapman J, Chen GL, Cooper D, Coutinho PM, Couturier J, Covert S, Cronk Q, et al: The genome of black cottonwood, Populus trichocarpa (Torr. & Gray). Science. 2006, 313: 1596-1604. 10.1126/science.1128691.PubMedView ArticleGoogle Scholar
- Blomme T, Vandepoele K, De Bodt S, Simillion C, Maere S, Peer Van de Y: The gain and loss of genes during 600 million years of vertebrate evolution. Genome Biol. 2006, 7: R43-10.1186/gb-2006-7-5-r43.PubMedPubMed CentralView ArticleGoogle Scholar
- Seoighe C: Turning the clock back on ancient genome duplication. Curr Opin Genet Dev. 2003, 13: 636-643. 10.1016/j.gde.2003.10.005.PubMedView ArticleGoogle Scholar
- Blanc G, Wolfe KH: Widespread paleopolyploidy in model plant species inferred from age distributions of duplicate genes. Plant Cell. 2004, 16: 1667-1678. 10.1105/tpc.021345.PubMedPubMed CentralView ArticleGoogle Scholar
- Cui L, Wall PK, Leebens-Mack JH, Lindsay BG, Soltis DE, Doyle JJ, Soltis PS, Carlson JE, Arumuganathan K, Barakat A, Albert VA, Ma H, dePamphilis CW: Widespread genome duplications throughout the history of flowering plants. Genome Res. 2006, 16: 738-749. 10.1101/gr.4825606.PubMedPubMed CentralView ArticleGoogle Scholar
- Scannell DR, Byrne KP, Gordon JL, Wong S, Wolfe KH: Multiple rounds of speciation associated with reciprocal gene loss in polyploid yeasts. Nature. 2006, 440: 341-345. 10.1038/nature04562.PubMedView ArticleGoogle Scholar
- Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997, 25: 3389-3402. 10.1093/nar/25.17.3389.PubMedPubMed CentralView ArticleGoogle Scholar
- Zdobnov EM, Apweiler R: InterProScan - an integration platform for the signature-recognition methods in InterPro. Bioinformatics. 2001, 17: 847-848. 10.1093/bioinformatics/17.9.847.PubMedView ArticleGoogle Scholar
- Edgar RC: MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004, 32: 1792-1797. 10.1093/nar/gkh340.PubMedPubMed CentralView ArticleGoogle Scholar
- Capella-Gutierrez S, Silla-Martinez JM, Gabaldon T: trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics. 2009, 25: 1972-1973. 10.1093/bioinformatics/btp348.PubMedPubMed CentralView ArticleGoogle Scholar
- Jones DT, Taylor WR, Thornton JM: The rapid generation of mutation data matrices from protein sequences. Comput Appl Biosci. 1992, 8: 275-282.PubMedGoogle Scholar
- Felsenstein J: PHYLIP - Phylogeny Inference Package (version 3.2). Cladistics. 1989, 5: 164-166.Google Scholar
- Le SQ, Gascuel O: An improved general amino acid replacement matrix. Mol Biol Evol. 2008, 25: 1307-1320. 10.1093/molbev/msn067.PubMedView ArticleGoogle Scholar
- Stamatakis A: RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics. 2006, 22: 2688-2690. 10.1093/bioinformatics/btl446.PubMedView ArticleGoogle Scholar
- Anisimova M, Gascuel O: Approximate likelihood-ratio test for branches: A fast, accurate, and powerful alternative. Syst Biol. 2006, 55: 539-552. 10.1080/10635150600755453.PubMedView ArticleGoogle Scholar
- Guindon S, Gascuel O: A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol. 2003, 52: 696-704. 10.1080/10635150390235520.PubMedView ArticleGoogle Scholar
- Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000, 25: 25-29. 10.1038/75556.PubMedPubMed CentralView ArticleGoogle Scholar
- Gene Ontology. [http://www.geneontology.org]
- Bauer S, Grossmann S, Vingron M, Robinson PN: Ontologizer 2.0 - a multifunctional tool for GO term enrichment analysis and data exploration. Bioinformatics. 2008, 24: 1650-1651. 10.1093/bioinformatics/btn250.PubMedView ArticleGoogle Scholar
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