An experimentally determined evolutionary model dramatically improves phylogenetic fit.


Abstract

All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.

Submission Details

ID: zAqktrSK

Submitter: Shu-Ching Ou

Submission Date: March 1, 2019, 5:26 p.m.

Version: 1

Publication Details
Bloom JD,Mol Biol Evol (2014) An experimentally determined evolutionary model dramatically improves phylogenetic fit. PMID:24859245
Additional Information

Study Summary

Number of data points 9464
Proteins Nucleoprotein
Unique complexes 9463
Assays/Quantities/Protocols Experimental Assay: Preference
Libraries Variants for Nucleoprotein

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
5NQ0 2018-04-25 1.1 Porcine (Sus scrofa) Major Histocompatibility Complex, class I, presenting DFEREGYSL
5NPZ 2018-05-02 1.43 Porcine (Sus scrofa) Major Histocompatibility Complex, class I, presenting EFEDLTFLA
5NQ2 2018-04-25 1.54 'Porcine (Sus scrofa) Major Histocompatibility Complex, class I, presenting IAYERMCNI
5NQ3 2018-04-25 1.57 'Porcine (Sus scrofa) Major Histocompatibility Complex, class I, with human beta2 micro globulin, presenting EFEDLTFLA
5GJY 2017-05-10 1.71 Crystal structure of DUCK MHC CLASS I for 1.71 angstrom
2WFS 2009-07-07 12.0 Fitting of influenza virus NP structure into the 9-fold symmetryzed cryoEM reconstruction of an active RNP particle.
4NQX 2013-12-25 2.0 Crystal Structure of HLA A*0101 in complex with NP44-S7N, an 9-mer influenza epitope
5GJX 2017-05-10 2.06 Crystal structure of DUCK MHC I for 2.06 angstrom
2BST 2005-05-24 2.1 Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA-B2705
5NQ1 2018-04-25 2.14 Porcine (Sus scrofa) Major Histocompatibility Complex, class I, with human beta2 micro globulin, presenting DFEREGYSL
5V5O 2018-03-14 2.24 Structure of NLS2K of influenza A virus nucleoprotein bound to importin alpha
4ZDU 2015-10-21 2.3 Crystal structure of importin-alpha bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein
4NQV 2013-12-25 2.39 Crystal Structure of HLA A*0101 in complex with NP44, an 9-mer influenza epitope
4MJ5 2014-10-08 2.4 Crystal Structure of HLA-A*1101 in complex with H1-22, an influenza A(H1N1) virus epitope
1HOC 1994-04-30 2.4 THE THREE-DIMENSIONAL STRUCTURE OF H-2DB AT 2.4 ANGSTROMS RESOLUTION: IMPLICATIONS FOR ANTIGEN-DETERMINANT SELECTION
4MJ6 2014-10-08 2.57 Crystal Structure of HLA-A*1101 in complex with H7-22, an influenza A(H7N9) virus epitope
5SWZ 2016-10-05 2.65 Crystal Structure of NP1-B17 TCR-H2Db-NP complex
3ZDP 2013-04-17 2.69 R416A Monomeric nucleoprotein of influenza A virus
5SWS 2016-10-05 2.86 Crystal Structure of NP2-B17 TCR-H2Db-NP complex
5B7B 2016-07-06 3.0 Crystal structure of Nucleoprotein-nucleozin complex

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
99.6 Nucleoprotein P22435 NCAP_I68A4
99.4 Nucleoprotein P03467 NCAP_I68A6
98.4 Nucleoprotein P16986 NCAP_I76AA
98.4 Nucleoprotein P26073 NCAP_I68A2
98.0 Nucleoprotein P06827 NCAP_I72A2
97.8 Nucleoprotein Q08041 NCAP_I72A4
97.8 Nucleoprotein Q1PUD5 NCAP_I73A5
97.2 Nucleoprotein Q3YPZ1 NCAP_I71A1
97.4 Nucleoprotein P16314 NCAP_I79A4
97.6 Nucleoprotein Q08033 NCAP_I76A6
97.8 Nucleoprotein A4K147 NCAP_I54A2
97.8 Nucleoprotein P26071 NCAP_I55A0
97.6 Nucleoprotein Q08031 NCAP_I73A3
97.4 Nucleoprotein Q08034 NCAP_I78A7
97.4 Nucleoprotein Q08035 NCAP_I78A8
97.6 Nucleoprotein A4U7B0 NCAP_I51A0
97.4 Nucleoprotein Q08028 NCAP_I75A0
97.4 Nucleoprotein P18072 NCAP_I77AH
97.2 Nucleoprotein Q9E5Y8 NCAP_I77A4
97.6 Nucleoprotein P26072 NCAP_I57A5
97.4 Nucleoprotein P21433 NCAP_I60A0
97.2 Nucleoprotein Q07531 NCAP_I73A2
96.8 Nucleoprotein P18070 NCAP_I78A6
96.6 Nucleoprotein Q08036 NCAP_I80A4
96.6 Nucleoprotein P16982 NCAP_I83A8
97.2 Nucleoprotein P18071 NCAP_I50A0
96.6 Nucleoprotein Q09159 NCAP_I77A5
96.4 Nucleoprotein Q07546 NCAP_I86A1
96.4 Nucleoprotein O91743 NCAP_I93A0
96.2 Nucleoprotein Q07548 NCAP_I80A3
96.6 Nucleoprotein P26069 NCAP_I40A0
96.0 Nucleoprotein Q07550 NCAP_I87A0
96.0 Nucleoprotein P69294 NCAP_I85A0
96.0 Nucleoprotein P69293 NCAP_I87A2
96.0 Nucleoprotein P69295 NCAP_I88A3
96.0 Nucleoprotein P69289 NCAP_I89A0
96.0 Nucleoprotein P69290 NCAP_I89A1
96.0 Nucleoprotein P69291 NCAP_I89A2
96.0 Nucleoprotein P69292 NCAP_I89A3
96.0 Nucleoprotein P69296 NCAP_I89A4
96.6 Nucleoprotein P18073 NCAP_I77AB
96.0 Nucleoprotein Q07545 NCAP_I88A2
95.8 Nucleoprotein Q07552 NCAP_I80A0
95.8 Nucleoprotein P26070 NCAP_I47A0
96.6 Nucleoprotein P18069 NCAP_I77AA
95.8 Nucleoprotein Q08042 NCAP_I90A0
95.8 Nucleoprotein P26090 NCAP_I83A0
96.0 Nucleoprotein P23997 NCAP_I83A2
95.8 Nucleoprotein A4GCK1 NCAP_I80AA
95.6 Nucleoprotein A4GCH9 NCAP_I83A1
95.2 Nucleoprotein Q289M3 NCAP_I00A1
95.0 Nucleoprotein A4GCL2 NCAP_I43A0
95.2 Nucleoprotein A3DRP4 NCAP_I96A2
94.8 Nucleoprotein A4U6V6 NCAP_I45A0
95.0 Nucleoprotein A8C8J8 NCAP_I07A0
95.0 Nucleoprotein Q07FI1 NCAP_I96A3
94.2 Nucleoprotein A4GCJ0 NCAP_I36A0
94.4 Nucleoprotein A4GCM3 NCAP_I35A3
94.0 Nucleoprotein P15682 NCAP_I33A0
94.0 Nucleoprotein P03466 NCAP_I34A1
93.8 Nucleoprotein P31609 NCAP_I54A0
93.8 Nucleoprotein P26089 NCAP_I35A1
93.8 Nucleoprotein B4URE0 NCAP_I06A0
93.6 Nucleoprotein Q5UEW0 NCAP_I18A0
92.6 Nucleoprotein P07381 NCAP_I73A0
92.6 Nucleoprotein P69299 NCAP_I77A3
92.6 Nucleoprotein P69297 NCAP_I82A0
92.6 Nucleoprotein P69298 NCAP_I82A1
92.4 Nucleoprotein Q0A2G1 NCAP_I83A4
92.4 Nucleoprotein Q9Q0U8 NCAP_I96A0
92.6 Nucleoprotein P26054 NCAP_I72A6
92.2 Nucleoprotein P26055 NCAP_I53A0
92.4 Nucleoprotein O90385 NCAP_I80A6
92.2 Nucleoprotein Q6DPD2 NCAP_I02A7
92.4 Nucleoprotein P68881 NCAP_I69A1
92.4 Nucleoprotein P68880 NCAP_I74A2
92.4 Nucleoprotein P15664 NCAP_I76AK
92.4 Nucleoprotein P68882 NCAP_I80A8
92.2 Nucleoprotein P26062 NCAP_I56A2
92.4 Nucleoprotein P26064 NCAP_I78A5
92.4 Nucleoprotein P26091 NCAP_I82A4
92.6 Nucleoprotein P15678 NCAP_I85A4
92.4 Nucleoprotein P26052 NCAP_I76AE
92.4 Nucleoprotein Q0A444 NCAP_I49A1
92.2 Nucleoprotein P15662 NCAP_I56A1
92.4 Nucleoprotein P15681 NCAP_I61A0
92.4 Nucleoprotein Q20P01 NCAP_I68A3
92.0 Nucleoprotein Q809S1 NCAP_I01A3
92.0 Nucleoprotein Q6J8B1 NCAP_I02A5
92.0 Nucleoprotein Q6DPE5 NCAP_I02A6
92.0 Nucleoprotein Q6J8C0 NCAP_I03A0
91.8 Nucleoprotein Q6DPE9 NCAP_I02A1
91.8 Nucleoprotein Q6DPE8 NCAP_I02A2
92.2 Nucleoprotein Q3SBF2 NCAP_I66A1
92.2 Nucleoprotein P21931 NCAP_I72A5
92.2 Nucleoprotein P26065 NCAP_I80A1
92.2 Nucleoprotein P15663 NCAP_I60A2
92.0 Nucleoprotein P06826 NCAP_I78A3
92.0 Nucleoprotein P26066 NCAP_I80A5
92.2 Nucleoprotein P15676 NCAP_I85A7
91.8 Nucleoprotein Q6DPC7 NCAP_I03A1
92.2 Nucleoprotein P16984 NCAP_I49A0
91.8 Nucleoprotein Q809S5 NCAP_I01A0
92.0 Nucleoprotein P26078 NCAP_I42A0
92.0 Nucleoprotein P16985 NCAP_I81A0
91.8 Nucleoprotein P15661 NCAP_I83A5
92.2 Nucleoprotein P26063 NCAP_I62A0
91.8 Nucleoprotein Q8QPJ5 NCAP_I00A0
91.8 Nucleoprotein P26060 NCAP_I81A3
91.6 Nucleoprotein Q809S9 NCAP_I01A1
92.2 Nucleoprotein P16978 NCAP_I75A2
92.0 Nucleoprotein P18277 NCAP_I76A0
91.8 Nucleoprotein P26059 NCAP_I77AE
91.4 Nucleoprotein P15660 NCAP_I77AG
92.0 Nucleoprotein P16983 NCAP_I84A3
91.6 Nucleoprotein Q6DPE6 NCAP_I02A4
91.8 Nucleoprotein P26080 NCAP_I49A2
91.8 Nucleoprotein P26053 NCAP_I80A2
91.8 Nucleoprotein P12604 NCAP_I34A0
91.4 Nucleoprotein Q6DPE7 NCAP_I02A3
91.6 Nucleoprotein Q0A2H2 NCAP_I59A0
91.6 Nucleoprotein P68042 NCAP_I88A5
91.6 Nucleoprotein P68043 NCAP_I88A7
91.6 Nucleoprotein P26082 NCAP_I57A7
91.6 Nucleoprotein P26068 NCAP_I89A7
91.8 Nucleoprotein P26056 NCAP_I66A0
92.0 Nucleoprotein P15671 NCAP_I79A7
91.4 Nucleoprotein P26076 NCAP_I35A2
91.4 Nucleoprotein O92784 NCAP_I97A1
91.4 Nucleoprotein P15677 NCAP_I30A0
91.4 Nucleoprotein P26085 NCAP_I79A5
91.2 Nucleoprotein P26061 NCAP_I27A0
91.6 Nucleoprotein P26092 NCAP_I89A6
91.6 Nucleoprotein P26077 NCAP_I37A0
91.2 Nucleoprotein Q67356 NCAP_I67A2
91.4 Nucleoprotein P15679 NCAP_I77AC
91.4 Nucleoprotein P16988 NCAP_I76AF
91.2 Nucleoprotein P26084 NCAP_I76AG
91.4 Nucleoprotein P26087 NCAP_I81A4
91.0 Nucleoprotein P26081 NCAP_I54A1
91.0 Nucleoprotein P26083 NCAP_I61A1
91.0 Nucleoprotein P26079 NCAP_I46A1
91.0 Nucleoprotein P26086 NCAP_I81A1
91.2 Nucleoprotein Q809S7 NCAP_I01A2
90.8 Nucleoprotein P16987 NCAP_I82A7
90.8 Nucleoprotein P16979 NCAP_I63A2
90.8 Nucleoprotein P15673 NCAP_I73A4
90.4 Nucleoprotein P15667 NCAP_I79A8
90.4 Nucleoprotein P15683 NCAP_I84A2
90.6 Nucleoprotein Q6TXC0 NCAP_I85A5
90.6 Nucleoprotein P26074 NCAP_I76A7
90.2 Nucleoprotein P15670 NCAP_I80AD
90.2 Nucleoprotein P15665 NCAP_I77AF
90.2 Nucleoprotein P15669 NCAP_I80AC
90.4 Nucleoprotein P67914 NCAP_I86A2
90.4 Nucleoprotein P67915 NCAP_I86A3
90.2 Nucleoprotein P15666 NCAP_I78AF
91.3 Nucleoprotein Q2LFN9 NCAP_I05A1