Abstract
RAG1 protein is one of the key component of RAG complex regulating the V(D)J recombination. There are only few studies for RAG1 concerning evolutionary history, detailed sequence and mutational hotspots. Herein, we present out datasets used for the recent comprehensive study of RAG1 based on sequence, phylogenetic and genetic variant analyses (Kumar et al., 2015) [1]. Protein sequence alignment helped in characterizing the conserved domains and regions of RAG1. It also aided in unraveling ancestral RAG1 in the sea urchin. Human genetic variant analyses revealed 751 mutational hotspots, located both in the coding and the non-coding regions. For further analysis and discussion, see (Kumar et al., 2015) [1].
Specifications Table
| Subject area | Biology |
| More specific subject area | Molecular evolution and bioinformatics |
| Type of data | Tables, figures |
| How data was acquired | Retrieved from public databases |
| Data format | Analyzed data |
| Experimental factors | RAG1 sequences were retrieved from ENSEMBL and/or NCBI database. |
| Experimental features | RAG1 protein alignment using Muscle tool and edited in the GeneDoc |
| RAG1 Variants were analyzed with SIFT, Polyphen & rSNPbase | |
| Data source location | Germany |
| Data accessibility | Data is with this article |
Value of the data
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Protein sequence analysis data reveal that SpRAG1L possesses only 19–20% identities with vertebrate RAG1, which helped us in deriving an ancestral RAG1 protein in sea urchin. This approach can be used the detection of origins for different proteins.
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Protein sequence alignment locates two major domains and several regions of RAG1, which suggested that these fragments were conserved from sea urchin to human. This hints evolutionary conservation of protein domains in the protein of interest and their ancestors.
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Data on the genetic variant analysis suggests that human RAG1 gene has 751 variants.
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Furthermore, there are 267 missense variants of human RAG1 causes change in amino acids including 140 deleterious mutations. These variant data serve as the mutational hotspots within the coding region of human RAG1. Assessment of mutational hotspot for any protein is critically important for understanding its function and roles in diseases.
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Additionally, 284 non-coding variants were identified with 94% regulatory in nature, which are often called as regulatory SNP (rSNP). These data are source of regulatory implications flanking any given gene.
1. Data
Table 1 lists all RAG1 sequences used in Kumar et al. [1] and these sequences are used for constructing protein sequence alignment of RAG1 (Fig. S1). This protein alignment is the basis for the Figs. 2 and 3 and Table 1–5 of Kumar et al. [1]. Details of human RAG1 variants are summarized in the Table S1 and regulatory SNPs in the Table S2. These two supplementary tables are primary data for variant analyses described in Fig. 4 and Tables 2–5 of Kumar et al. [1].
Table 1.
Summary of RAG1 from selected animal genomes. This data is collected from Ensembl database release 77 . At times data is gathered from additional databases as indicated.
| Name | Organism | Species | Accession id | Chromosomal localization |
|---|---|---|---|---|
| HsapRAG1 | Human | Homo sapiens | ENSG00000166349 | Chromosome 11: 36,532,259-36,614,706 |
| MmusRAG1 | Mouse | Mus musculus | ENSMUSG00000061311 | Chromosome 2: 101,638,282-101,649,501 |
| RnorRAG1 | Rat | Rattus norvegicus | ENSRNOG00000004630 | Chromosome 3: 97,866,048-97,877,145 |
| TgutRAG1 | Zebrafinch | Taeniopygia guttata | ENSTGUG00000010147 | Chromosome 5: 17,596,747-17,599,869 |
| MgalRAG1 | Turkey | Meleagris gallopavo | ENSMGAG00000015794 | Chromosome 5: 19,778,620-19,781,748 |
| PsinRAG1 | Turtle | Pelodiscus sinensis | ENSPSIG00000001811 | Scaffold JH209124.1: 1,890,899-1,894,018 |
| DrerRAG1 | Zebrafish | Danio rerio | ENSDARG00000052122 | Chromosome 25: 9,231,637-9,238,142 |
| TrubRAG1 | Fugu | Takifugu rubripes | ENSTRUG00000001340 | scaffold_302: 189,544-193,510 |
| TnigRAG1 | Tetraodon | Tetraodon nigroviridis | ENSTNIG00000012168 | Chromosome 13: 5,598,243-5,602,176 |
| OnilRAG1 | Tilapia | Oreochromis niloticus | ENSONIG00000014593 | Scaffold GL831142.1: 1,924,501-1,931,477 |
| GmorRAG1a | Cod | Gadus morhua | ENSGMOG00000003395 | GeneScaffold_2196: 249,630-253,939 |
| XmacRAG1 | Platyfish | Xiphophorus maculatus | ENSXMAG00000000820 | Scaffold JH556735.1: 897,221-901,222 |
| GacuRAG1 | Stickleback | Gasterosteus aculeatus | ENSGACG00000011465 | groupXIX: 14,493,756-14,497,787 |
| OlatRAG1 | Medaka | Oryzias latipes | ENSORLG00000011969 | Chromosome 6: 17,343,305-17,347,405 |
| LchaRAG1 | Coelacanth | Latimeria chalumnae | ENSLACG00000004406 | Scaffold JH126568.1: 121,275-124,451 |
| VpaRAG1 | Alpaca | Vicugna pacos | ENSVPAG00000008826 | GeneScaffold_2429: 269,595-273,365 |
| AcarRAG1 | Anole lizard | Anolis carolinensis | ENSACAG00000005106 | Chromosome 1: 53,518,235-53,521,375 |
| DnoRAG1 | Armadillo | Dasypus novemcinctus | ENSDNOG00000006294 | Scaffold JH582431.1: 4,276,543-4,279,674 |
| OgarRAG1 | Bushbaby | Otolemur garnettii | ENSOGAG00000027339 | Scaffold GL873520.1: 63,167,240-63,168,052 |
| FcatRAG1 | Cat | Felis catus | ENSFCAG00000002908 | Chromosome D1: 92,125,946-92,129,077 |
| AmeRAG1 | Cave fish | Astyanax mexicanus | ENSAMXG00000017587 | Scaffold KB871579.1: 5,211,103-5,217,994 |
| PtroRAG1 | Chimpanzee | Pan troglodytes | ENSPTRG00000003512 | Chromosome 11: 36,559,562-36,571,320 |
| BtauRAG1 | Cow | Bos taurus | ENSBTAG00000040293 | Chromosome 15: 67,827,233-67,830,364 |
| CfamRAG1 | Dog | Canis lupus familiaris | ENSCAFG00000006808 | Chromosome 18: 31,631,533-31,634,664 |
| TtruRAG1 | Dolphin | Tursiops truncatus | ENSTTRG00000014075 | scaffold_110171: 196,070-199,540 |
| AplaRAG1 | Duck | Anas platyrhynchos | ENSAPLG00000011756 | Scaffold KB742537.1: 887,774-890,899 |
| LafrRAG1 | Elephant | Loxodonta africana | ENSLAFG00000023175 | SuperContig scaffold_21: 12,902,400-12,905,531 |
| MfurRAG1 | Ferret | Mustela putorius furo | ENSMPUG00000019963 | Scaffold GL896949.1: 10,184,818-10,187,949 |
| FalbRAG1 | Flycatcher | Ficedula albicollis | ENSFALG00000014372 | Scaffold JH603235.1: 3,494,497-3,497,619 |
| NleuRAG1 | Gibbon | Nomascus leucogenys | ENSNLEG00000017951 | SuperContig GL397264.1: 51,275,048-51,286,754 |
| GgorRAG1 | Gorilla | Gorilla gorilla gorilla | ENSGGOG00000013132 | Chromosome 11: 37,187,229-37,198,984 |
| CporRAG1 | Guinea Pig | Cavia porcellus | ENSCPOG00000004516 | scaffold_92: 2,485,274-2,488,405 |
| EcabRAG1 | Horse | Equus caballus | ENSECAG00000021936 | Chromosome 12: 3,025,356-3,033,251 |
| PcapRAG1 | Hyrax | Procavia capensis | ENSPCAG00000001732 | GeneScaffold_5497: 13,553-16,990 |
| MmulRAG1 | Macaque | Macaca mulatta | ENSMMUG00000018267 | Scaffold 1099214286323: 4,563-7,694 |
| CjacRAG1 | Marmoset | Callithrix jacchus | ENSCJAG00000011082 | Chromosome 11: 99,857,897-99,869,593 |
| MlucRAG1 | Microbat | Myotis lucifugus | ENSMLUG00000000544 | Scaffold GL430055: 356,167-359,298 |
| MmurRAG1 | Mouse Lemur | Microcebus murinus | ENSMICG00000008611 | GeneScaffold_3288: 841,983-845,201 |
| MdomRAG1 | Oppossum | Monodelphis domestica | ENSMODG00000024470 | Chromosome 5: 272,756,599-272,759,742 |
| AmelRAG1 | Panda | Ailuropoda melanoleuca | ENSAMEG00000019378 | Scaffold GL193442.1: 461,741-464,872 |
| SscrRAG1 | Pig | Sus scrofa | ENSSSCG00000026145 | Chromosome 2: 26,730,010-26,738,216 |
| OanaRAG1 | Platypus | Ornithorhynchus anatinus | ENSOANG00000011770 | Chromosome 3: 11,364,602-11,365,783 |
| OcunRAG1 | Rabbit | Oryctolagus cuniculus | ENSOCUG00000006989 | Chromosome 1: 175,828,096-175,831,224 |
| OarRAG1 | Sheep | Ovis aries | ENSOARG00000010441 | Chromosome 15: 65,210,839-65,213,970 |
| SaraRAG1 | Shrew | Sorex araneus | ENSSARG00000010950 | GeneScaffold_5915: 66,723-69,956 |
| LocRAG1 | Spotted gar | Lepisosteus oculatus | ENSLOCG00000001283 | Chromosome LG27: 1,403,519-1,420,074 |
| ItriRAG1 | Squirrel | Ictidomys tridecemlineatus | ENSSTOG00000025584 | Scaffold JH393343.1: 1,817,576-1,820,707 |
| TsyrRAG1 | Tarsier | Tarsius syrichta | ENSTSYG00000007158 | scaffold_7240: 21,771-24,902 |
| SharRAG1 | Tasmanian devil | Sarcophilus harrisii | ENSSHAG00000014085 | Scaffold GL864890.1: 1,391,366-1,394,509 |
| TbeRAG1 | Tree Shrew | Tupaia belangeri | ENSTBEG00000003010 | GeneScaffold_4067: 865-4,810 |
| MeuRAG1 | Wallaby | Macropus eugenii | ENSMEUG00000003165 | Scaffold77145: 3,005-5,812 |
| XtroRAG1 | Xenopus | Xenopus tropicalis | ENSXETP00000016443/XP_002937338a | Scaffold GL172917.1: 903,952-910,208 |
| SpuRAG1L | Sea urchin | Strongylocentrotus purpuratus | AAZ23546.1a | NA |
From NCBI.
2. Experimental design, materials and methods
Using the BLAST homology detection tool [2], we extracted RAG1 gene from vertebrate genomes listed either in Ensembl release 77 [3] or NCBI. To ensure accuracy of gene structures, we combined the gene predictions of the Ensembl [3] and AUGUSTUS tool [4]. We used human RAG1 as the standard sequence for intron position mapping and numbering of intron positions, followed by suffixes a–c for their location as reported previously [5]. We aligned selected RAG1 protein sequences using MUSCLE tool [6] with and we manually adjusted alignment with GENEDOC tool [7]. We reconstructed a phylogenetic tree with maximum likelihood method, based on the JTT matrix-based model [8] with 1000 bootstrap replicates. We imported all consensus trees to MEGA 6 software [9], where we edited and visualized these trees as per requirement. To detect the orthologs of RAG1 gene, we analyzed micro-synteny across different genomes using two genome browsers namely, NCBI map viewer [10] and ENSEMBL genome browser [11], [12]. Furthermore, we generated human RAG1 variants from 1092 human genomes from 14 different populations available in 1000 genomes project [13]. We analyzed the impact assessments of missense variants on the human RAG1 protein using SIFT [14] and PolyPhen V2 [15] tools, as described previously [16], [17], [18], [19]. We detected regulatory nature of non-coding variants using the rSNPbase (this database provides reliable, and comprehensive regulatory annotations [20] and such variants are called regulatory SNP or rSNP).
Acknowledgments
We thank Faculty Recharge Programme of the University Grant Commission (UGC-FRP) and UPE II (PI#15) for the financial support to RT.
Footnotes
Supplementary data associated with this article can be found in the online version at 10.1016/j.dib.2016.05.021.
Appendix A. Supplementary material
Supplementary material Fig. S1. Protein sequence alignment of RAG1 from selected animal genome. Different domains and regions are marked above the alignment. Sequence identity scores of ≥85%, ≥65% and ≥45% are marked by red, blue and green shades respectively.
Supplementary material Table S1. Overview of 751 germline variants of RAG1 gene deduced from 1000 genome data.
Supplementary material Table S2. Overview of non-coding germline variants of Human RAG1.
Supplementary material
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Associated Data
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Supplementary Materials
Supplementary material Fig. S1. Protein sequence alignment of RAG1 from selected animal genome. Different domains and regions are marked above the alignment. Sequence identity scores of ≥85%, ≥65% and ≥45% are marked by red, blue and green shades respectively.
Supplementary material Table S1. Overview of 751 germline variants of RAG1 gene deduced from 1000 genome data.
Supplementary material Table S2. Overview of non-coding germline variants of Human RAG1.
Supplementary material