Functional Segregation of Overlapping Genes in HIV.


Abstract

Overlapping genes pose an evolutionary dilemma as one DNA sequence evolves under the selection pressures of multiple proteins. Here, we perform systematic statistical and mutational analyses of the overlapping HIV-1 genes tat and rev and engineer exhaustive libraries of non-overlapped viruses to perform deep mutational scanning of each gene independently. We find a "segregated" organization in which overlapped sites encode functional residues of one gene or the other, but never both. Furthermore, this organization eliminates unfit genotypes, providing a fitness advantage to the population. Our comprehensive analysis reveals the extraordinary manner in which HIV minimizes the constraint of overlapping genes and repurposes that constraint to its own advantage. Thus, overlaps are not just consequences of evolutionary constraints, but rather can provide population fitness advantages.

Submission Details

ID: CDVbKaNU4

Submitter: Marie Ary

Submission Date: June 28, 2018, 1:09 p.m.

Version: 1

Publication Details
Fernandes JD;Faust TB;Strauli NB;Smith C;Crosby DC;Nakamura RL;Hernandez RD;Frankel AD,Cell (2016) Functional Segregation of Overlapping Genes in HIV. PMID:27984726
Additional Information

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
6MCF 2018-10-31 Solution structure of 7SK stem-loop 1 with HIV-1 Tat RNA Binding Domain
6MCE 2018-10-31 Solution structure of HIV-1 TAR with Tat RNA Binding Domain
1RPV 1995-10-15 HIV-1 REV PROTEIN (RESIDUES 34-50)
6HIP 2019-03-27 1.2 Structure of SPF45 UHM bound to HIV-1 Rev ULM
3MI9 2010-06-09 2.1 Crystal structure of HIV-1 Tat complexed with human P-TEFb
5V61 2017-07-26 2.2 Phospho-ERK2 bound to bivalent inhibitor SBP2
6BSY 2018-04-11 2.25 HIV-1 Rev assembly domain (residues 1-69)
5DHV 2016-06-22 2.3 HIV-1 Rev NTD dimers with variable crossing angles
3LPH 2010-12-08 2.5 Crystal structure of the HIV-1 Rev dimer
4OR5 2014-04-16 2.9 Crystal structure of HIV-1 Tat complexed with human P-TEFb and AFF4
5DHX 2016-06-22 2.9 HIV-1 Rev NTD dimers with variable crossing angles
3MIA 2010-06-09 3.0 Crystal structure of HIV-1 Tat complexed with ATP-bound human P-TEFb
6CF2 2018-07-25 3.0 Crystal structure of HIV-1 Rev (residues 1-93)-RNA aptamer complex
5DHY 2016-06-22 3.1 HIV-1 Rev NTD dimers with variable crossing angles
2X7L 2010-03-23 3.17 Implications of the HIV-1 Rev dimer structure at 3.2A resolution for multimeric binding to the Rev response element
4PMI 2014-12-24 3.2 Crystal structure of Rev and Rev-response-element RNA complex
6CYT 2018-12-12 3.5 HIV-1 TAR loop in complex with Tat:AFF4:P-TEFb
5DHZ 2016-06-29 4.3 HIV-1 Rev NTD dimers with variable crossing angles

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
94.1 Protein Tat (HIV-1 HXB2) P19552 TAT_HV1S3
98.0 Protein Tat (HIV-1 HXB2) P04612 TAT_HV1B5
100.0 Protein Tat (HIV-1 HXB2) P04608 TAT_HV1H2
96.2 Protein Rev P05864 REV_HV1B8
92.2 Protein Rev P04623 REV_HV1A2
91.4 Protein Rev P05872 REV_HV1SC
93.1 Protein Rev P69718 REV_HV1H3
94.0 Protein Rev P04616 REV_HV1B1
94.0 Protein Rev P04325 REV_HV112
94.8 Protein Rev P04620 REV_HV1BR
99.1 Protein Rev P04618 REV_HV1H2
94.2 Protein Tat (HIV-1 NL4-3) P05907 TAT_HV1C4