GyDB org - User contributions [en]

Phylogeny:GagPol

2020-12-23T08:21:55Z

Rfutami:

[[Category:Phylogeny]]
{{Phylogeny
|map=<imagemap>
Image:GagPol.png|center
rect 340 1033 363 1047 [[Element:VMV|VMV]]
rect 340 1042 388 1056 [[Element:SA-OMVV|SA-OMVV]]
rect 340 1024 368 1038 [[Element:CAEV|CAEV]]
rect 340 1014 356 1028 [[Element:FIV|FIV]]
rect 340 732 367 746 [[Element:Mdg3|Mdg3]]
rect 340 741 384 755 [[Element:Blastopia|Blastopia]]
rect 340 723 382 737 [[Element:Micropia|Micropia]]
rect 340 596 364 610 [[Element:Woot|Woot]]
rect 340 605 378 619 [[Element:Osvaldo|Osvaldo]]
rect 340 614 365 628 [[Element:Circe|Circe]]
rect 340 623 373 637 [[Element:Ulysses|Ulysses]]
rect 340 641 362 655 [[Element:Cer3|Cer3]]
rect 340 650 362 664 [[Element:Cer2|Cer2]]
rect 340 632 362 646 [[Element:Cer1|Cer1]]
rect 340 705 362 719 [[Element:Cer5|Cer5]]
rect 340 714 362 728 [[Element:Cer6|Cer6]]
rect 340 696 362 710 [[Element:Cer4|Cer4]]
rect 340 687 377 701 [[Element:Gulliver|Gulliver]]
rect 340 678 361 692 [[Element:Mag|Mag]]
rect 340 668 367 682 [[Element:SURL|SURL]]
rect 340 659 368 673 [[Element:Cigr-1|Cigr-1]]
rect 340 31 365 45 [[Element:Cgret|Cgret]]
rect 340 40 364 54 [[Element:Pyret|Pyret]]
rect 340 22 371 36 [[Element:Skippy|Skippy]]
rect 340 13 362 27 [[Element:Cft-1|Cft-1]]
rect 340 49 371 63 [[Element:marY1|marY1]]
rect 340 59 387 73 [[Element:Sushi-ichi|Sushi-ichi]]
rect 340 68 372 82 [[Element:Maggy|Maggy]]
rect 340 77 374 91 [[Element:Dane-1|Dane-1]]
rect 340 86 376 100 [[Element:MGLR3|MGLR3]]
rect 340 104 362 118 [[Element:Real|Real]]
rect 340 113 369 127 [[Element:Pyggy|Pyggy]]
rect 340 95 398 109 [[Element:Grasshopper|Grasshopper]]
rect 340 131 363 145 [[Element:CRM|CRM]]
rect 340 140 374 154 [[Element:Cereba|Cereba]]
rect 340 122 377 136 [[Element:Beetle1|Beetle1]]
rect 340 150 384 164 [[Element:Galadriel|Galadriel]]
rect 340 159 376 173 [[Element:Monkey|Monkey]]
rect 340 168 377 182 [[Element:Tntom1|Tntom1]]
rect 340 195 366 209 [[Element:Gimli|Gimli]]
rect 340 204 368 218 [[Element:Reina|Reina]]
rect 340 186 358 200 [[Element:Ifg7|Ifg7]]
rect 340 177 366 191 [[Element:Gloin|Gloin]]
rect 340 213 377 227 [[Element:Legolas|Legolas]]
rect 340 222 362 236 [[Element:Tma|Tma]]
rect 340 231 356 245 [[Element:Del|Del]]
rect 340 250 387 264 [[Element:Retrosat-2|Retrosat-2]]
rect 340 259 373 273 [[Element:Bagy-1|Bagy-1]]
rect 340 241 382 255 [[Element:Peabody|Peabody]]
rect 340 277 367 291 [[Element:Ty3-1|Ty3-1]]
rect 340 286 375 300 [[Element:Skipper|Skipper]]
rect 340 268 363 282 [[Element:Tse3|Tse3]]
rect 340 295 359 309 [[Element:TF2|TF2]]
rect 340 304 359 318 [[Element:TF1|TF1]]
rect 340 313 372 327 [[Element:Kabuki|Kabuki]]
rect 340 323 371 337 [[Element:CsRN1|CsRN1]]
rect 340 341 364 355 [[Element:Yoyo|Yoyo]]
rect 340 350 400 364 [[Element:HMS-Beagle|HMS-Beagle]]
rect 340 332 374 346 [[Element:Nomad|Nomad]]
rect 340 368 380 382 [[Element:Springer|Springer]]
rect 340 377 379 391 [[Element:Gypsyvir|Gypsyvir]]
rect 340 386 368 400 [[Element:Gypsy|Gypsy]]
rect 340 359 378 373 [[Element:Burdock|Burdock]]
rect 340 395 361 409 [[Element:Zam|Zam]]
rect 340 404 359 418 [[Element:Ted|Ted]]
rect 340 414 366 428 [[Element:Idefix|Idefix]]
rect 340 423 358 437 [[Element:Tv1|Tv1]]
rect 340 441 362 455 [[Element:Tom|Tom]]
rect 340 450 358 464 [[Element:297|297]]
rect 340 432 361 446 [[Element:17.6|17.6]]
rect 340 459 367 473 [[Element:Mdg1|Mdg1]]
rect 340 468 358 482 [[Element:412|412]]
rect 340 486 370 500 [[Element:RIRE2|RIRE2]]
rect 340 495 390 509 [[Element:Grande1-4|Grande1-4]]
rect 340 505 399 519 [[Element:B1147A04.5|B1147A04.5]]
rect 340 514 377 528 [[Element:Cinful-1|Cinful-1]]
rect 340 523 387 537 [[Element:RetroSor1|RetroSor1]]
rect 340 532 371 546 [[Element:Tat4-1|Tat4-1]]
rect 340 541 359 555 [[Element:Tft2|Tft2]]
rect 340 477 363 491 [[Element:Ogre|Ogre]]
rect 340 550 386 564 [[Element:Cyclops-2|Cyclops-2]]
rect 340 559 383 573 [[Element:Athila4-1|Athila4-1]]
rect 340 568 381 582 [[Element:Diaspora|Diaspora]]
rect 340 577 373 591 [[Element:Bagy-2|Bagy-2]]
rect 340 587 377 601 [[Element:Calypso|Calypso]]
rect 340 778 361 792 [[Element:REV|REV]]
rect 340 814 367 828 [[Element:KoRV|KoRV]]
rect 340 823 368 837 [[Element:GALV|GALV]]
rect 340 805 369 819 [[Element:MdEV|MdEV]]
rect 340 796 393 810 [[Element:PERV-MSL|PERV-MSL]]
rect 340 787 377 801 [[Element:BAEVM|BAEVM]]
rect 340 841 385 855 [[Element:RCHO-K1|RCHO-K1]]
rect 340 851 368 865 [[Element:MuLV|MuLV]]
rect 340 832 365 846 [[Element:FeLV|FeLV]]
rect 340 769 378 783 [[Element:HERV-E|HERV-E]]
rect 340 760 379 774 [[Element:RTVL-Ia|RTVL-Ia]]
rect 340 750 369 764 [[Element:WdSV|WdSV]]
rect 340 869 360 883 [[Element:HFV|HFV]]
rect 340 878 369 892 [[Element:SFV-1|SFV-1]]
rect 340 860 385 874 [[Element:MuERV-L|MuERV-L]]
rect 340 896 376 910 [[Element:HTLV-1|HTLV-1]]
rect 340 905 417 919 [[Element:STcLV2PP1664|STcLV2PP1664]]
rect 340 914 376 928 [[Element:HTLV-2|HTLV-2]]
rect 340 887 360 901 [[Element:BLV|BLV]]
rect 340 969 370 983 [[Element:SRV-1|SRV-1]]
rect 340 978 372 992 [[Element:MPMV|MPMV]]
rect 340 960 368 974 [[Element:SERV|SERV]]
rect 340 951 380 965 [[Element:SMRV-H|SMRV-H]]
rect 340 942 366 956 [[Element:JSRV|JSRV]]
rect 340 932 372 946 [[Element:MMTV|MMTV]]
rect 340 923 390 937 [[Element:HERV-K10|HERV-K10]]
rect 340 987 367 1001 [[Element:LPDV|LPDV]]
rect 340 996 361 1010 [[Element:RSV|RSV]]
rect 340 1005 357 1019 [[Element:BIV|BIV]]
rect 340 1051 364 1065 [[Element:EIAV|EIAV]]
rect 340 1060 366 1074 [[Element:HIV-1|HIV-1]]
rect 340 1069 380 1083 [[Element:SIVMND|SIVMND]]
rect 340 1078 381 1092 [[Element:SIVAGM|SIVAGM]]
rect 340 1087 366 1101 [[Element:HIV-2|HIV-2]]
rect 340 1096 380 1110 [[Element:SIVMAC|SIVMAC]]
</imagemap>
|method=Phylogenetic reconstruction inferred based on the concatenated protein product
encoded by the gag-pro-pol internal region common to Ty3/Gypsy and Retroviridae LTR
retroelements using FelsensteinÂ´s protein sequence parsimony method based on (Eck
and Dayhoff 1966) and (Fitch 1971) to generate a majority-rule consensus tree
(Margush and McMorris 1981). As majority-rule consensus tree usually consists of all
groups that occur more than 50% of the time, we take consensus values upper to 50 as
an equivalent-bootstrapping reference.
}}

Flowchart

2020-12-23T07:03:00Z

Rfutami:

<table>
<tr><td style="padding-right:20px;">

==The clan AA Reference Database (CAARD)==
The clan AA Reference Database (CAARD) is an attempt at characterizing the clan AA protein domain in all its possible phylogenetic signals by ancestral maximum likelihood reconstruction (AMLRs), sequence logos and hidden Markov models (HMMs). With this aim, we performed a comprehensive study of 323 non-redundant clan AA peptidases (CAPs) dividing them into 38 protein families according to prior estimates of their taxonomy and relationships (for more details see Table 1 in [[#References|Llorens et. al.]]). In this section we describe the bioinformatic flowchart designed to normalize and characterize the different signals. The flowchart can be divided in 4 steps, a description of each step follows.

==Multiple alignments and consensus identification==
Because the different families present in the current database were originally assumed from prior investigations, we compared all sequences to each other via the [[BLAST|BLAST search at GyDB using the CORES Database in BLASTp mode]]. With very few exceptions, the BLAST analysis confirmed that each family follows a particular phylogenetic signal, or in other words, that the sequences belonging to each family are usually more similar to one another than to other sequences (data not shown). From that point on, we created a set of 34 alignments, one for each family that includes 2 or more CAPs to characterize the protein domain architecture of each family (we dismissed the CAPs representing one-sequence families from the 38 families summarized in Table 1 of [[#References|Llorens et. al.]]). Additionally, we performed a non-redundant single multiple alignment with all CAPs to evaluate the phylogeny and major consensus. Here, we used prior structure-based alignments ([[#References|Pearl and Taylor 1987]]; [[#References|Weber 1989]]) and Andreeva's model ([[#References|Andreeva 1991]]) as the criterion to manually align the different families. The alignment was refined using a [[Phylogeny:Clan_AA|conventional phylogeny]] as guide tree. While performing this alignment, we identified 6 amino acid patterns with structural correspondence with Andreeva's model. We will refer to these patterns as the DTG/ILG template because of the DT/SG and ILG amino acid motifs ([[#References|Pearl and Blundell 1984]]; [[#References|Pearl and Taylor 1987]]) usually found in all CAPs are prominent. Alignments are freely available in the GyDB collection deposited in Biotechvana Bioinformatics (for more details see [[#References|Llorens et al.]]).

==Information content enhancement==
Clan AA is an extremely difficult case study of fast evolving protein. Software algorithms fail to align exhaustively the different clan AA families and the degree of sequence preservation varies depending on the family. This means that while many families show high degree of preservation, others have not sufficient information content by themselves. To overcome this limitation, we used each family alignment as an input to FastML ([[#References|Pupko et al 2000]]) to reconstruct by phylogenetic means a set of AMLR sequences by 2 alternative methods, Joint and Marginal ([[#References|Aldrich 1997]]; [[#References|Koshi and Goldstein 1996]]; [[#References|Pupko, Pe'er, Shamir, and Graur 2000]]; [[#References|Yang et al 1995]]). The AMLR analysis provides several files with information about different aspects of the AMLR analysis (this includes 2 Jrof and Mrof alignments between CAPs and AMLR sequences). Here, we do not try to reconstruct the single ancestor of each family (statistically, this probability approaches 0), but a variety of ancestral states to enhance the information content of each family alignment. With this, the object of the AMLR analysis is to increase the most prominent sequence patterns specifically preserved by each set of monophyletic CAPs (the main principle we tested in previous steps is, sequences belonging to a monophyletic family are more similar to each other than any other sequence).

==HMMs and sequence logos==
We selected the AMLR alignments, removed the non-informative traits from all of them, and used those obtained with the Jrof method to create a collection of HMM profiles and sequence logos, with HMMER ([[#References|HMMER 2008]]) and [http://gydb.uv.es/servers/checkAlign/checkalign_form.php CheckAlign], respectively. We used the processed AMLR alignments instead of conventional alignments to minimize conflicting signals among families in the HMMs, and build the sequence logos taking advantage of the information content enhancement. Finally, we constructed a set of MRC sequences derived from the HMMs using HMMER. HMMs and the MRCs were tested using the COREs database via the [[BLAST|BLAST]] and [[HMM|HMM]] searches at GyDB, in BLASTp and hmmsearch, respectively.

==Major consensus==
We tested different tools to characterize the DTG/ILG template as a sequence logo or as an HMM profile using the non-redundant alignment as input. Because of the variability and multiple gaps introduced in the alignment, all tools failed to reconstruct informative material. In an attempt to increase the information content of the non-redundant alignment, we conducted an additional AMLR analysis using this alignment as an input to FastML. This strategy also failed to obtain an AMLR alignment with sufficient information content for creating a sequence logo or an HMM. Then, we tried an alternative strategy, anchoring the MRCs derived from HMMs in a single master alignment manually based on the 6 DTG/ILG template's patterns. To cover all possible sequence states in this alignment we also aligned the LTRCAPs representing one-sequence families dismissed from the set of alignments. We performed an additional AMLR analysis using this alignment as an input to FastML and removed the non-informative traits from the resultant AMLR alignments (as we did with the other AMLR alignments used to create HMMs and sequences logos). In the Figure P1 within this section, we show the resolved Jrof alignment from this analysis, after the processing of non-informative traits. Again, we would stress that performing AMLR we did not try to resolve any kind of relationship between input and AMLR sequences. The goal was to enhance the most prominent sequence patterns of the master alignment to build an informative computational material. Taking into account the large number of Ty3/Gypsy MRCs used in the analysis, we conducted a second AMLR analysis excluding all these sequences from the master alignment. Figure P2 shows the Jrof alignments resolved from this alternative AMLR analysis, after the processing of non-informative traits. Both AMLRs had sufficient information content to create a sequence logo and an HMM profile. We tested the 2 HMMs with the different MRCs involved in their reconstruction and with all CAPs originally classified using the [[HMM|HMM]] sever available at GyDB. Both HMMs showed strong similarity to the different MRCs (Table P1) and displayed a wide range of similarity detection when comparing them to CAPs. However, the HMM implemented by Ty3/Gypsy sequences proved more capable than the alternative HMM, as it covers more states than the alternative model.

==Cite this bioinformatic flowchart and Database==
Llorens,C. Futami, R., Renaud, G. and A. Moya. Bioinformatic Flowchart and database to investigate the origins and diversity of clan AA peptidases. (manuscript accepted, Biology Direct)

==References==
*Aldrich,J., 1997. R.A. Fischer and the making of Maximum Likelihood 1912-1922. [[Literature:85472|Statistical Science 12, 162-176.]]
*Andreeva,N.S., 1991. A consensus template for the aspartic proteinase fold. [[Literature:1876|Adv. Exp. Med. Biol. 306, 559-572]].
*HMMER. http://hmmer.janelia.org/. 2008. Ref Type: Grant
*Koshi,J.M., Goldstein,R.A., 1996. Probabilistic reconstruction of ancestral protein sequences. [[Literature:85467|J. Mol. Evol. 42, 313-320]].
*Pearl,L., Blundell,T., 1984. The active site of aspartic proteinases. [[Literature:85462|FEBS Lett. 174, 96-101]].
*Pearl,L.H., Taylor,W.R., 1987. A structural model for the retroviral proteases. [[Literature:58377|Nature 329, 351-354]].
*Pupko,T., Pe'er,I., Shamir,R., Graur,D., 2000. A fast algorithm for joint reconstruction of ancestral amino acid sequences. [[Literature:61282|Molecular Biology and Evolution 17, 890-896]].
*Schneider,T.D., 2002. Consensus sequence Zen. Appl. Bioinformatics 1, 111-119.
*Weber,I.T., 1989. Structural Alignment of Retroviral Protease Sequences. [[Literature:81897|Gene 85, 565-566]].
*Yang,Z., Kumar,S., Nei,M., 1995. A new method of inference of ancestral nucleotide and amino acid sequences. [[Literature:85468|Genetics 141, 1641-1650]].
</td>
<td style="vertical-align:top">

<table style="width:200px;float:right;">
<tr><td>
<imagemap>
Image:Flowchart_F1.png
rect 0 0 200 138 [http://gydb.uv.es/gydbModules/caard/images/figure_P1.htm]
</imagemap>
Figure P1 - Ancestral ML reconstruction of the DTG/ILG template. We anchored the HMM-derived MRCs in a master alignment along with several sequences constituting one-sequence families, using the 6 amino acid patterns delineated by the DTG/ILG template as a reference. Then, we increased the information content of this alignment using AMLR. The figure shows the Jrof alignment reported by the AMLR analysis after the processing of non-informative traits. The 6 amino acid patterns of the DTG/ILG template are underlined. Sequences identified from N1 to N36 are the AMLR sequences, a detail of their relationships with the input CAPs is available in the database under "results".
</td></tr>
<tr><td>
<imagemap>
Image:Flowchart_F2.png
rect 0 0 200 78 [http://gydb.uv.es/gydbModules/caard/images/figure_P2.htm]
</imagemap>
Figure P2 - DTG/ILG template reconstruction without Ty3/Gypsy sequences.
Because of the number of Ty3/Gypsy sequences used in the first DTG/ILG template AMLR analysis, we performed an alternative analysis dismissing the Ty3/Gypsy sequence. The 6 amino acid patterns of the DTG/ILG template are underlined. Sequences identified from N1 to N19 are the AMLR sequences. A detail of their relationships with the input CAPs is available in the database under "results".
</td></tr>
<tr><td>
<imagemap>
Image:Flowchart_T1.png
rect 0 0 200 270 [http://gydb.uv.es/gydbModules/caard/images/table_P1.htm]
</imagemap>
Table P1 - Comparison were conducted using the MRC sequences as queries to the HMM profiles using HMMER with hmmpfam.
</td></tr>
</table>

</td>
</tr>
</table>