Human and Mouse Gene Structure: Comparative Analysis and Application to Exon Prediction

Batzoglou, Serafim; Pachter, Lior; Mesirov, Jill P.; Berger, Bonnie; Lander, Eric S.

doi:10.1101/gr.10.7.950

Cited by 316 publications

(216 citation statements)

References 20 publications

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“…Accordingly, all TBCID3-coding exons are identical in length to those of RNTRE, with the exception of the last one, which also contains the 3Ј untranslated regions (UTRs; Figure 1B and Figure S1 in Supplementary Material). Gene structure conservation is a common feature among ortholog and paralog genes, and it has been proposed to represent a record of key events in evolution, even when protein sequence similarity is low (Batzoglou et al, 2000;Betts et al, 2001;Koonin, 2005). This applies to TBC1D3, which despite having originated only after the initial primate radiation (ϳ60 million years ago; Paulding et al, 2003), accumulated, in a remarkably short period of time, a considerable number of mutations, accounting for the relatively low degree of similarity between the TBC1D3 and RNTRE gene products ( Figure S2 in Supplementary Material).…”

Section: Tbc1d3 the Paralog Of Human Rntre Underwent Gene Duplicatimentioning

confidence: 99%

The Primate-specific Protein TBC1D3 Is Required for Optimal Macropinocytosis in a Novel ARF6-dependent Pathway

Frittoli

Palamidessi

Pizzigoni

et al. 2008

MBoC

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The generation of novel genes and proteins throughout evolution has been proposed to occur as a result of whole genome and gene duplications, exon shuffling, and retrotransposition events. The analysis of such genes might thus shed light into the functional complexity associated with highly evolved species. One such case is represented by TBC1D3, a primatespecific gene, harboring a TBC domain. Because TBC domains encode Rab-specific GAP activities, TBC-containing proteins are predicted to play a major role in endocytosis and intracellular traffic. Here, we show that the TBC1D3 gene originated late in evolution, likely through a duplication of the RNTRE locus, and underwent gene amplification during primate speciation. Despite possessing a TBC domain, TBC1D3 is apparently devoid of Rab-GAP activity. However, TBC1D3 regulates the optimal rate of epidermal growth factor-mediated macropinocytosis by participating in a novel pathway involving ARF6 and RAB5. In addition, TBC1D3 binds and colocalize to GGA3, an ARF6-effector, in an ARF6-dependent manner, and synergize with it in promoting macropinocytosis, suggesting that the two proteins act together in this process. Accordingly, GGA3 siRNA-mediated ablation impaired TBC1D3-induced macropinocytosis. We thus uncover a novel signaling pathway that appeared after primate speciation. Within this pathway, a TBC1D3:GGA3 complex contributes to optimal propagation of signals, ultimately facilitating the macropinocytic process. INTRODUCTIONGene duplication, exon shuffling, and retrotransposition events played crucial roles during vertebrate evolution (Long, 2001;McLysaght et al., 2002;Brosius, 2003). About 5% of the human genome is composed of duplicated segments that emerged during the past 35 million years of primate evolution, resulting in the generation of novel protein functions (Courseaux and Nahon, 2001;Taylor and Raes, 2004).One of the cellular processes, whose regulation has became more and more complex and tightly regulated during evolution is endocytosis. Endocytosis serves to maintain cellular and organismal homeostasis by mediating the uptake of fluids, solutes, and signaling molecules and their receptors. Multiple mechanisms of endocytosis operate within a single cell (Conner and Schmid, 2003). Among them, two major categories are phagocytosis and pinocytosis, which mediate the uptake of particles or of fluid, respectively (Conner and Schmid, 2003).Pinocytosis encompasses a variety of different membraneentry routes and is invariably characterized by the relatively small size (50 -150 nm) of the internalized particles. Large volumes of fluid are, instead, engulfed by extension, folding, and closure of plasma membranes (PM) through a process termed macropinocytosis (Swanson and Watts, 1995). Macropinocytosis displays many similarities to phagocytosis; the biochemical and cellular components of these endocytic mechanisms have been best characterized in hematopoietic cells, in processes such as phagocytosis by macrophages in response to Fc receptor stimulation, or ma...

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Section: Tbc1d3 the Paralog Of Human Rntre Underwent Gene Duplicatimentioning

confidence: 99%

The Primate-specific Protein TBC1D3 Is Required for Optimal Macropinocytosis in a Novel ARF6-dependent Pathway

Frittoli

Palamidessi

Pizzigoni

et al. 2008

MBoC

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“…There is some overlap between the SCIMOG and MIT data sets, and thus the latter cannot properly be called a test set. However, we decided not to eliminate the redundant entries, so that the results could be compared to those published for the ROSSETA program (Batzoglou et al 2000). …”

Section: Benchmark Sequence Setsmentioning

confidence: 99%

“…To test the accuracy of SGP2, we used the data set constructed by Batzoglou et al (2000) of 117 orthologous human and mouse genes. We discarded those pairs in which in at least one of the sequences contained multiple genes, and those in which the coding region started in position 1 in one of the sequences of the pair.…”

Section: Benchmark Sequence Setsmentioning

confidence: 99%

“…The programs ROSSETA (Batzoglou et al 2000), SGP1 (from 'syntenic gene prediction'; Wiehe et al 2001), and C E M ( f r o m ' c o n s e r v e d e x o n method'; Bafna and Huson 2000) are representative of this approach. All these programs start by aligning two syntenic sequences and then predict gene structures in which the exons are compatible with the alignment.…”

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Comparative Gene Prediction in Human and Mouse

Parra

Agarwal²,

Abril³

et al. 2003

Genome Res.

189

108

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The completion of the sequencing of the mouse genome promises to help predict human genes with greater accuracy. While current ab initio gene prediction programs are remarkably sensitive (i.e., they predict at least a fragment of most genes), their specificity is often low, predicting a large number of false-positive genes in the human genome. Sequence conservation at the protein level with the mouse genome can help eliminate some of those false positives. Here we describe SGP2, a gene prediction program that combines ab initio gene prediction with TBLASTX searches between two genome sequences to provide both sensitive and specific gene predictions. The accuracy of SGP2 when used to predict genes by comparing the human and mouse genomes is assessed on a number of data sets, including single-gene data sets, the highly curated human chromosome 22 predictions, and entire genome predictions from ENSEMBL. Results indicate that SGP2 outperforms purely ab initio gene prediction methods. Results also indicate that SGP2 works about as well with 3x shotgun data as it does with fully assembled genomes. SGP2 provides a high enough specificity that its predictions can be experimentally verified at a reasonable cost. SGP2 was used to generate a complete set of gene predictions on both the human and mouse by comparing the genomes of these two species. Our results suggest that another few thousand human and mouse genes currently not in ENSEMBL are worth verifying experimentally

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“…The first tools developed for alignment of longer genomic regions, such as GLASS (Batzoglou et al 2000), AVID , and BLASTZ (Schwartz et al 2003), could not align more than two DNA sequences. At the same time multiple alignment tools, such as ClustalW (Thompson et al 1994) and DIALIGN (Morgenstern et al 1998;Morgenstern 2000), could not handle more than a few kilobases of sequence.…”

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confidence: 99%

Multiple whole-genome alignments without a reference organism

Dubchak

Poliakov²,

Kislyuk³

et al. 2009

Genome Res.

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Multiple sequence alignments have become one of the most commonly used resources in genomics research. Most algorithms for multiple alignment of whole genomes rely either on a reference genome, against which all of the other sequences are laid out, or require a one-to-one mapping between the nucleotides of the genomes, preventing the alignment of recently duplicated regions. Both approaches have drawbacks for whole-genome comparisons. In this paper we present a novel symmetric alignment algorithm. The resulting alignments not only represent all of the genomes equally well, but also include all relevant duplications that occurred since the divergence from the last common ancestor. Our algorithm, implemented as a part of the VISTA Genome Pipeline (VGP), was used to align seven vertebrate and six Drosophila genomes. The resulting whole-genome alignments demonstrate a higher sensitivity and specificity than the pairwise alignments previously available through the VGP and have higher exon alignment accuracy than comparable public whole-genome alignments. Of the multiple alignment methods tested, ours performed the best at aligning genes from multigene families—perhaps the most challenging test for whole-genome alignments. Our whole-genome multiple alignments are available through the VISTA Browser at http://genome.lbl.gov/vista/index.shtml.

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Human and Mouse Gene Structure: Comparative Analysis and Application to Exon Prediction

Cited by 316 publications

References 20 publications

The Primate-specific Protein TBC1D3 Is Required for Optimal Macropinocytosis in a Novel ARF6-dependent Pathway

The Primate-specific Protein TBC1D3 Is Required for Optimal Macropinocytosis in a Novel ARF6-dependent Pathway

Comparative Gene Prediction in Human and Mouse

Multiple whole-genome alignments without a reference organism

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