---
_id: '6419'
abstract:
- lang: eng
text: Characterizing the fitness landscape, a representation of fitness for a large
set of genotypes, is key to understanding how genetic information is interpreted
to create functional organisms. Here we determined the evolutionarily-relevant
segment of the fitness landscape of His3, a gene coding for an enzyme in the histidine
synthesis pathway, focusing on combinations of amino acid states found at orthologous
sites of extant species. Just 15% of amino acids found in yeast His3 orthologues
were always neutral while the impact on fitness of the remaining 85% depended
on the genetic background. Furthermore, at 67% of sites, amino acid replacements
were under sign epistasis, having both strongly positive and negative effect in
different genetic backgrounds. 46% of sites were under reciprocal sign epistasis.
The fitness impact of amino acid replacements was influenced by only a few genetic
backgrounds but involved interaction of multiple sites, shaping a rugged fitness
landscape in which many of the shortest paths between highly fit genotypes are
inaccessible.
article_number: e1008079
article_processing_charge: No
author:
- first_name: Victoria
full_name: Pokusaeva, Victoria
id: 3184041C-F248-11E8-B48F-1D18A9856A87
last_name: Pokusaeva
orcid: 0000-0001-7660-444X
- first_name: Dinara R.
full_name: Usmanova, Dinara R.
last_name: Usmanova
- first_name: Ekaterina V.
full_name: Putintseva, Ekaterina V.
last_name: Putintseva
- first_name: Lorena
full_name: Espinar, Lorena
last_name: Espinar
- first_name: Karen
full_name: Sarkisyan, Karen
id: 39A7BF80-F248-11E8-B48F-1D18A9856A87
last_name: Sarkisyan
orcid: 0000-0002-5375-6341
- first_name: Alexander S.
full_name: Mishin, Alexander S.
last_name: Mishin
- first_name: Natalya S.
full_name: Bogatyreva, Natalya S.
last_name: Bogatyreva
- first_name: Dmitry
full_name: Ivankov, Dmitry
id: 49FF1036-F248-11E8-B48F-1D18A9856A87
last_name: Ivankov
- first_name: Arseniy
full_name: Akopyan, Arseniy
id: 430D2C90-F248-11E8-B48F-1D18A9856A87
last_name: Akopyan
orcid: 0000-0002-2548-617X
- first_name: Sergey
full_name: Avvakumov, Sergey
id: 3827DAC8-F248-11E8-B48F-1D18A9856A87
last_name: Avvakumov
- first_name: Inna S.
full_name: Povolotskaya, Inna S.
last_name: Povolotskaya
- first_name: Guillaume J.
full_name: Filion, Guillaume J.
last_name: Filion
- first_name: Lucas B.
full_name: Carey, Lucas B.
last_name: Carey
- first_name: Fyodor
full_name: Kondrashov, Fyodor
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
citation:
ama: Pokusaeva V, Usmanova DR, Putintseva EV, et al. An experimental assay of the
interactions of amino acids from orthologous sequences shaping a complex fitness
landscape. PLoS Genetics. 2019;15(4). doi:10.1371/journal.pgen.1008079
apa: Pokusaeva, V., Usmanova, D. R., Putintseva, E. V., Espinar, L., Sarkisyan,
K., Mishin, A. S., … Kondrashov, F. (2019). An experimental assay of the interactions
of amino acids from orthologous sequences shaping a complex fitness landscape.
PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1008079
chicago: Pokusaeva, Victoria, Dinara R. Usmanova, Ekaterina V. Putintseva, Lorena
Espinar, Karen Sarkisyan, Alexander S. Mishin, Natalya S. Bogatyreva, et al. “An
Experimental Assay of the Interactions of Amino Acids from Orthologous Sequences
Shaping a Complex Fitness Landscape.” PLoS Genetics. Public Library of
Science, 2019. https://doi.org/10.1371/journal.pgen.1008079.
ieee: V. Pokusaeva et al., “An experimental assay of the interactions of
amino acids from orthologous sequences shaping a complex fitness landscape,” PLoS
Genetics, vol. 15, no. 4. Public Library of Science, 2019.
ista: Pokusaeva V, Usmanova DR, Putintseva EV, Espinar L, Sarkisyan K, Mishin AS,
Bogatyreva NS, Ivankov D, Akopyan A, Avvakumov S, Povolotskaya IS, Filion GJ,
Carey LB, Kondrashov F. 2019. An experimental assay of the interactions of amino
acids from orthologous sequences shaping a complex fitness landscape. PLoS Genetics.
15(4), e1008079.
mla: Pokusaeva, Victoria, et al. “An Experimental Assay of the Interactions of Amino
Acids from Orthologous Sequences Shaping a Complex Fitness Landscape.” PLoS
Genetics, vol. 15, no. 4, e1008079, Public Library of Science, 2019, doi:10.1371/journal.pgen.1008079.
short: V. Pokusaeva, D.R. Usmanova, E.V. Putintseva, L. Espinar, K. Sarkisyan, A.S.
Mishin, N.S. Bogatyreva, D. Ivankov, A. Akopyan, S. Avvakumov, I.S. Povolotskaya,
G.J. Filion, L.B. Carey, F. Kondrashov, PLoS Genetics 15 (2019).
date_created: 2019-05-13T07:58:38Z
date_published: 2019-04-10T00:00:00Z
date_updated: 2023-08-25T10:30:37Z
day: '10'
ddc:
- '570'
department:
- _id: FyKo
doi: 10.1371/journal.pgen.1008079
ec_funded: 1
external_id:
isi:
- '000466866000029'
file:
- access_level: open_access
checksum: cf3889c8a8a16053dacf9c3776cbe217
content_type: application/pdf
creator: dernst
date_created: 2019-05-14T08:26:08Z
date_updated: 2020-07-14T12:47:30Z
file_id: '6445'
file_name: 2019_PLOSGenetics_Pokusaeva.pdf
file_size: 3726017
relation: main_file
file_date_updated: 2020-07-14T12:47:30Z
has_accepted_license: '1'
intvolume: ' 15'
isi: 1
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: PLoS Genetics
publication_identifier:
eissn:
- '15537404'
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
record:
- id: '9789'
relation: research_data
status: public
- id: '9790'
relation: research_data
status: public
- id: '9797'
relation: research_data
status: public
scopus_import: '1'
status: public
title: An experimental assay of the interactions of amino acids from orthologous sequences
shaping a complex fitness landscape
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 15
year: '2019'
...
---
_id: '9789'
article_processing_charge: No
author:
- first_name: Victoria
full_name: Pokusaeva, Victoria
id: 3184041C-F248-11E8-B48F-1D18A9856A87
last_name: Pokusaeva
orcid: 0000-0001-7660-444X
- first_name: Dinara R.
full_name: Usmanova, Dinara R.
last_name: Usmanova
- first_name: Ekaterina V.
full_name: Putintseva, Ekaterina V.
last_name: Putintseva
- first_name: Lorena
full_name: Espinar, Lorena
last_name: Espinar
- first_name: Karen
full_name: Sarkisyan, Karen
id: 39A7BF80-F248-11E8-B48F-1D18A9856A87
last_name: Sarkisyan
orcid: 0000-0002-5375-6341
- first_name: Alexander S.
full_name: Mishin, Alexander S.
last_name: Mishin
- first_name: Natalya S.
full_name: Bogatyreva, Natalya S.
last_name: Bogatyreva
- first_name: Dmitry
full_name: Ivankov, Dmitry
id: 49FF1036-F248-11E8-B48F-1D18A9856A87
last_name: Ivankov
- first_name: Arseniy
full_name: Akopyan, Arseniy
id: 430D2C90-F248-11E8-B48F-1D18A9856A87
last_name: Akopyan
orcid: 0000-0002-2548-617X
- first_name: Sergey
full_name: Avvakumov, Sergey
id: 3827DAC8-F248-11E8-B48F-1D18A9856A87
last_name: Avvakumov
- first_name: Inna S.
full_name: Povolotskaya, Inna S.
last_name: Povolotskaya
- first_name: Guillaume J.
full_name: Filion, Guillaume J.
last_name: Filion
- first_name: Lucas B.
full_name: Carey, Lucas B.
last_name: Carey
- first_name: Fyodor
full_name: Kondrashov, Fyodor
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
citation:
ama: Pokusaeva V, Usmanova DR, Putintseva EV, et al. Multiple alignment of His3
orthologues. 2019. doi:10.1371/journal.pgen.1008079.s010
apa: Pokusaeva, V., Usmanova, D. R., Putintseva, E. V., Espinar, L., Sarkisyan,
K., Mishin, A. S., … Kondrashov, F. (2019). Multiple alignment of His3 orthologues.
Public Library of Science. https://doi.org/10.1371/journal.pgen.1008079.s010
chicago: Pokusaeva, Victoria, Dinara R. Usmanova, Ekaterina V. Putintseva, Lorena
Espinar, Karen Sarkisyan, Alexander S. Mishin, Natalya S. Bogatyreva, et al. “Multiple
Alignment of His3 Orthologues.” Public Library of Science, 2019. https://doi.org/10.1371/journal.pgen.1008079.s010.
ieee: V. Pokusaeva et al., “Multiple alignment of His3 orthologues.” Public
Library of Science, 2019.
ista: Pokusaeva V, Usmanova DR, Putintseva EV, Espinar L, Sarkisyan K, Mishin AS,
Bogatyreva NS, Ivankov D, Akopyan A, Avvakumov S, Povolotskaya IS, Filion GJ,
Carey LB, Kondrashov F. 2019. Multiple alignment of His3 orthologues, Public Library
of Science, 10.1371/journal.pgen.1008079.s010.
mla: Pokusaeva, Victoria, et al. Multiple Alignment of His3 Orthologues.
Public Library of Science, 2019, doi:10.1371/journal.pgen.1008079.s010.
short: V. Pokusaeva, D.R. Usmanova, E.V. Putintseva, L. Espinar, K. Sarkisyan, A.S.
Mishin, N.S. Bogatyreva, D. Ivankov, A. Akopyan, S. Avvakumov, I.S. Povolotskaya,
G.J. Filion, L.B. Carey, F. Kondrashov, (2019).
date_created: 2021-08-06T08:38:50Z
date_published: 2019-04-10T00:00:00Z
date_updated: 2023-08-25T10:30:36Z
day: '10'
department:
- _id: FyKo
doi: 10.1371/journal.pgen.1008079.s010
month: '04'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '6419'
relation: used_in_publication
status: public
status: public
title: Multiple alignment of His3 orthologues
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2019'
...
---
_id: '9790'
article_processing_charge: No
author:
- first_name: Victoria
full_name: Pokusaeva, Victoria
id: 3184041C-F248-11E8-B48F-1D18A9856A87
last_name: Pokusaeva
orcid: 0000-0001-7660-444X
- first_name: Dinara R.
full_name: Usmanova, Dinara R.
last_name: Usmanova
- first_name: Ekaterina V.
full_name: Putintseva, Ekaterina V.
last_name: Putintseva
- first_name: Lorena
full_name: Espinar, Lorena
last_name: Espinar
- first_name: Karen
full_name: Sarkisyan, Karen
id: 39A7BF80-F248-11E8-B48F-1D18A9856A87
last_name: Sarkisyan
orcid: 0000-0002-5375-6341
- first_name: Alexander S.
full_name: Mishin, Alexander S.
last_name: Mishin
- first_name: Natalya S.
full_name: Bogatyreva, Natalya S.
last_name: Bogatyreva
- first_name: Dmitry
full_name: Ivankov, Dmitry
id: 49FF1036-F248-11E8-B48F-1D18A9856A87
last_name: Ivankov
- first_name: Arseniy
full_name: Akopyan, Arseniy
id: 430D2C90-F248-11E8-B48F-1D18A9856A87
last_name: Akopyan
orcid: 0000-0002-2548-617X
- first_name: Sergey
full_name: Avvakumov, Sergey
id: 3827DAC8-F248-11E8-B48F-1D18A9856A87
last_name: Avvakumov
- first_name: Inna S.
full_name: Povolotskaya, Inna S.
last_name: Povolotskaya
- first_name: Guillaume J.
full_name: Filion, Guillaume J.
last_name: Filion
- first_name: Lucas B.
full_name: Carey, Lucas B.
last_name: Carey
- first_name: Fyodor
full_name: Kondrashov, Fyodor
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
citation:
ama: Pokusaeva V, Usmanova DR, Putintseva EV, et al. A statistical summary of segment
libraries and sequencing results. 2019. doi:10.1371/journal.pgen.1008079.s011
apa: Pokusaeva, V., Usmanova, D. R., Putintseva, E. V., Espinar, L., Sarkisyan,
K., Mishin, A. S., … Kondrashov, F. (2019). A statistical summary of segment libraries
and sequencing results. Public Library of Science. https://doi.org/10.1371/journal.pgen.1008079.s011
chicago: Pokusaeva, Victoria, Dinara R. Usmanova, Ekaterina V. Putintseva, Lorena
Espinar, Karen Sarkisyan, Alexander S. Mishin, Natalya S. Bogatyreva, et al. “A
Statistical Summary of Segment Libraries and Sequencing Results.” Public Library
of Science, 2019. https://doi.org/10.1371/journal.pgen.1008079.s011.
ieee: V. Pokusaeva et al., “A statistical summary of segment libraries and
sequencing results.” Public Library of Science, 2019.
ista: Pokusaeva V, Usmanova DR, Putintseva EV, Espinar L, Sarkisyan K, Mishin AS,
Bogatyreva NS, Ivankov D, Akopyan A, Avvakumov S, Povolotskaya IS, Filion GJ,
Carey LB, Kondrashov F. 2019. A statistical summary of segment libraries and sequencing
results, Public Library of Science, 10.1371/journal.pgen.1008079.s011.
mla: Pokusaeva, Victoria, et al. A Statistical Summary of Segment Libraries and
Sequencing Results. Public Library of Science, 2019, doi:10.1371/journal.pgen.1008079.s011.
short: V. Pokusaeva, D.R. Usmanova, E.V. Putintseva, L. Espinar, K. Sarkisyan, A.S.
Mishin, N.S. Bogatyreva, D. Ivankov, A. Akopyan, S. Avvakumov, I.S. Povolotskaya,
G.J. Filion, L.B. Carey, F. Kondrashov, (2019).
date_created: 2021-08-06T08:50:15Z
date_published: 2019-04-10T00:00:00Z
date_updated: 2023-08-25T10:30:36Z
day: '10'
department:
- _id: FyKo
doi: 10.1371/journal.pgen.1008079.s011
month: '04'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '6419'
relation: used_in_publication
status: public
status: public
title: A statistical summary of segment libraries and sequencing results
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2019'
...
---
_id: '9797'
article_processing_charge: No
author:
- first_name: Victoria
full_name: Pokusaeva, Victoria
id: 3184041C-F248-11E8-B48F-1D18A9856A87
last_name: Pokusaeva
orcid: 0000-0001-7660-444X
- first_name: Dinara R.
full_name: Usmanova, Dinara R.
last_name: Usmanova
- first_name: Ekaterina V.
full_name: Putintseva, Ekaterina V.
last_name: Putintseva
- first_name: Lorena
full_name: Espinar, Lorena
last_name: Espinar
- first_name: Karen
full_name: Sarkisyan, Karen
id: 39A7BF80-F248-11E8-B48F-1D18A9856A87
last_name: Sarkisyan
orcid: 0000-0002-5375-6341
- first_name: Alexander S.
full_name: Mishin, Alexander S.
last_name: Mishin
- first_name: Natalya S.
full_name: Bogatyreva, Natalya S.
last_name: Bogatyreva
- first_name: Dmitry
full_name: Ivankov, Dmitry
id: 49FF1036-F248-11E8-B48F-1D18A9856A87
last_name: Ivankov
- first_name: Arseniy
full_name: Akopyan, Arseniy
id: 430D2C90-F248-11E8-B48F-1D18A9856A87
last_name: Akopyan
orcid: 0000-0002-2548-617X
- first_name: Inna S.
full_name: Povolotskaya, Inna S.
last_name: Povolotskaya
- first_name: Guillaume J.
full_name: Filion, Guillaume J.
last_name: Filion
- first_name: Lucas B.
full_name: Carey, Lucas B.
last_name: Carey
- first_name: Fyodor
full_name: Kondrashov, Fyodor
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
citation:
ama: Pokusaeva V, Usmanova DR, Putintseva EV, et al. A statistical summary of segment
libraries and sequencing results. 2019. doi:10.1371/journal.pgen.1008079.s011
apa: Pokusaeva, V., Usmanova, D. R., Putintseva, E. V., Espinar, L., Sarkisyan,
K., Mishin, A. S., … Kondrashov, F. (2019). A statistical summary of segment libraries
and sequencing results. Public Library of Science. https://doi.org/10.1371/journal.pgen.1008079.s011
chicago: Pokusaeva, Victoria, Dinara R. Usmanova, Ekaterina V. Putintseva, Lorena
Espinar, Karen Sarkisyan, Alexander S. Mishin, Natalya S. Bogatyreva, et al. “A
Statistical Summary of Segment Libraries and Sequencing Results.” Public Library
of Science, 2019. https://doi.org/10.1371/journal.pgen.1008079.s011.
ieee: V. Pokusaeva et al., “A statistical summary of segment libraries and
sequencing results.” Public Library of Science, 2019.
ista: Pokusaeva V, Usmanova DR, Putintseva EV, Espinar L, Sarkisyan K, Mishin AS,
Bogatyreva NS, Ivankov D, Akopyan A, Povolotskaya IS, Filion GJ, Carey LB, Kondrashov
F. 2019. A statistical summary of segment libraries and sequencing results, Public
Library of Science, 10.1371/journal.pgen.1008079.s011.
mla: Pokusaeva, Victoria, et al. A Statistical Summary of Segment Libraries and
Sequencing Results. Public Library of Science, 2019, doi:10.1371/journal.pgen.1008079.s011.
short: V. Pokusaeva, D.R. Usmanova, E.V. Putintseva, L. Espinar, K. Sarkisyan, A.S.
Mishin, N.S. Bogatyreva, D. Ivankov, A. Akopyan, I.S. Povolotskaya, G.J. Filion,
L.B. Carey, F. Kondrashov, (2019).
date_created: 2021-08-06T11:08:20Z
date_published: 2019-04-10T00:00:00Z
date_updated: 2023-08-25T10:30:36Z
day: '10'
department:
- _id: FyKo
doi: 10.1371/journal.pgen.1008079.s011
month: '04'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '6419'
relation: used_in_publication
status: public
status: public
title: A statistical summary of segment libraries and sequencing results
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2019'
...
---
_id: '5780'
abstract:
- lang: eng
text: Bioluminescence is found across the entire tree of life, conferring a spectacular
set of visually oriented functions from attracting mates to scaring off predators.
Half a dozen different luciferins, molecules that emit light when enzymatically
oxidized, are known. However, just one biochemical pathway for luciferin biosynthesis
has been described in full, which is found only in bacteria. Here, we report identification
of the fungal luciferase and three other key enzymes that together form the biosynthetic
cycle of the fungal luciferin from caffeic acid, a simple and widespread metabolite.
Introduction of the identified genes into the genome of the yeast Pichia pastoris
along with caffeic acid biosynthesis genes resulted in a strain that is autoluminescent
in standard media. We analyzed evolution of the enzymes of the luciferin biosynthesis
cycle and found that fungal bioluminescence emerged through a series of events
that included two independent gene duplications. The retention of the duplicated
enzymes of the luciferin pathway in nonluminescent fungi shows that the gene duplication
was followed by functional sequence divergence of enzymes of at least one gene
in the biosynthetic pathway and suggests that the evolution of fungal bioluminescence
proceeded through several closely related stepping stone nonluminescent biochemical
reactions with adaptive roles. The availability of a complete eukaryotic luciferin
biosynthesis pathway provides several applications in biomedicine and bioengineering.
article_processing_charge: No
author:
- first_name: Alexey A.
full_name: Kotlobay, Alexey A.
last_name: Kotlobay
- first_name: Karen
full_name: Sarkisyan, Karen
id: 39A7BF80-F248-11E8-B48F-1D18A9856A87
last_name: Sarkisyan
orcid: 0000-0002-5375-6341
- first_name: Yuliana A.
full_name: Mokrushina, Yuliana A.
last_name: Mokrushina
- first_name: Marina
full_name: Marcet-Houben, Marina
last_name: Marcet-Houben
- first_name: Ekaterina O.
full_name: Serebrovskaya, Ekaterina O.
last_name: Serebrovskaya
- first_name: Nadezhda M.
full_name: Markina, Nadezhda M.
last_name: Markina
- first_name: Louisa
full_name: Gonzalez Somermeyer, Louisa
id: 4720D23C-F248-11E8-B48F-1D18A9856A87
last_name: Gonzalez Somermeyer
orcid: 0000-0001-9139-5383
- first_name: Andrey Y.
full_name: Gorokhovatsky, Andrey Y.
last_name: Gorokhovatsky
- first_name: Andrey
full_name: Vvedensky, Andrey
last_name: Vvedensky
- first_name: Konstantin V.
full_name: Purtov, Konstantin V.
last_name: Purtov
- first_name: Valentin N.
full_name: Petushkov, Valentin N.
last_name: Petushkov
- first_name: Natalja S.
full_name: Rodionova, Natalja S.
last_name: Rodionova
- first_name: Tatiana V.
full_name: Chepurnyh, Tatiana V.
last_name: Chepurnyh
- first_name: Liliia
full_name: Fakhranurova, Liliia
last_name: Fakhranurova
- first_name: Elena B.
full_name: Guglya, Elena B.
last_name: Guglya
- first_name: Rustam
full_name: Ziganshin, Rustam
last_name: Ziganshin
- first_name: Aleksandra S.
full_name: Tsarkova, Aleksandra S.
last_name: Tsarkova
- first_name: Zinaida M.
full_name: Kaskova, Zinaida M.
last_name: Kaskova
- first_name: Victoria
full_name: Shender, Victoria
last_name: Shender
- first_name: Maxim
full_name: Abakumov, Maxim
last_name: Abakumov
- first_name: Tatiana O.
full_name: Abakumova, Tatiana O.
last_name: Abakumova
- first_name: Inna S.
full_name: Povolotskaya, Inna S.
last_name: Povolotskaya
- first_name: Fedor M.
full_name: Eroshkin, Fedor M.
last_name: Eroshkin
- first_name: Andrey G.
full_name: Zaraisky, Andrey G.
last_name: Zaraisky
- first_name: Alexander S.
full_name: Mishin, Alexander S.
last_name: Mishin
- first_name: Sergey V.
full_name: Dolgov, Sergey V.
last_name: Dolgov
- first_name: Tatiana Y.
full_name: Mitiouchkina, Tatiana Y.
last_name: Mitiouchkina
- first_name: Eugene P.
full_name: Kopantzev, Eugene P.
last_name: Kopantzev
- first_name: Hans E.
full_name: Waldenmaier, Hans E.
last_name: Waldenmaier
- first_name: Anderson G.
full_name: Oliveira, Anderson G.
last_name: Oliveira
- first_name: Yuichi
full_name: Oba, Yuichi
last_name: Oba
- first_name: Ekaterina
full_name: Barsova, Ekaterina
last_name: Barsova
- first_name: Ekaterina A.
full_name: Bogdanova, Ekaterina A.
last_name: Bogdanova
- first_name: Toni
full_name: Gabaldón, Toni
last_name: Gabaldón
- first_name: Cassius V.
full_name: Stevani, Cassius V.
last_name: Stevani
- first_name: Sergey
full_name: Lukyanov, Sergey
last_name: Lukyanov
- first_name: Ivan V.
full_name: Smirnov, Ivan V.
last_name: Smirnov
- first_name: Josef I.
full_name: Gitelson, Josef I.
last_name: Gitelson
- first_name: Fyodor
full_name: Kondrashov, Fyodor
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
- first_name: Ilia V.
full_name: Yampolsky, Ilia V.
last_name: Yampolsky
citation:
ama: Kotlobay AA, Sarkisyan K, Mokrushina YA, et al. Genetically encodable bioluminescent
system from fungi. Proceedings of the National Academy of Sciences of the United
States of America. 2018;115(50):12728-12732. doi:10.1073/pnas.1803615115
apa: Kotlobay, A. A., Sarkisyan, K., Mokrushina, Y. A., Marcet-Houben, M., Serebrovskaya,
E. O., Markina, N. M., … Yampolsky, I. V. (2018). Genetically encodable bioluminescent
system from fungi. Proceedings of the National Academy of Sciences of the United
States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.1803615115
chicago: Kotlobay, Alexey A., Karen Sarkisyan, Yuliana A. Mokrushina, Marina Marcet-Houben,
Ekaterina O. Serebrovskaya, Nadezhda M. Markina, Louisa Gonzalez Somermeyer, et
al. “Genetically Encodable Bioluminescent System from Fungi.” Proceedings of
the National Academy of Sciences of the United States of America. National
Academy of Sciences, 2018. https://doi.org/10.1073/pnas.1803615115.
ieee: A. A. Kotlobay et al., “Genetically encodable bioluminescent system
from fungi,” Proceedings of the National Academy of Sciences of the United
States of America, vol. 115, no. 50. National Academy of Sciences, pp. 12728–12732,
2018.
ista: Kotlobay AA, Sarkisyan K, Mokrushina YA, Marcet-Houben M, Serebrovskaya EO,
Markina NM, Gonzalez Somermeyer L, Gorokhovatsky AY, Vvedensky A, Purtov KV, Petushkov
VN, Rodionova NS, Chepurnyh TV, Fakhranurova L, Guglya EB, Ziganshin R, Tsarkova
AS, Kaskova ZM, Shender V, Abakumov M, Abakumova TO, Povolotskaya IS, Eroshkin
FM, Zaraisky AG, Mishin AS, Dolgov SV, Mitiouchkina TY, Kopantzev EP, Waldenmaier
HE, Oliveira AG, Oba Y, Barsova E, Bogdanova EA, Gabaldón T, Stevani CV, Lukyanov
S, Smirnov IV, Gitelson JI, Kondrashov F, Yampolsky IV. 2018. Genetically encodable
bioluminescent system from fungi. Proceedings of the National Academy of Sciences
of the United States of America. 115(50), 12728–12732.
mla: Kotlobay, Alexey A., et al. “Genetically Encodable Bioluminescent System from
Fungi.” Proceedings of the National Academy of Sciences of the United States
of America, vol. 115, no. 50, National Academy of Sciences, 2018, pp. 12728–32,
doi:10.1073/pnas.1803615115.
short: A.A. Kotlobay, K. Sarkisyan, Y.A. Mokrushina, M. Marcet-Houben, E.O. Serebrovskaya,
N.M. Markina, L. Gonzalez Somermeyer, A.Y. Gorokhovatsky, A. Vvedensky, K.V. Purtov,
V.N. Petushkov, N.S. Rodionova, T.V. Chepurnyh, L. Fakhranurova, E.B. Guglya,
R. Ziganshin, A.S. Tsarkova, Z.M. Kaskova, V. Shender, M. Abakumov, T.O. Abakumova,
I.S. Povolotskaya, F.M. Eroshkin, A.G. Zaraisky, A.S. Mishin, S.V. Dolgov, T.Y.
Mitiouchkina, E.P. Kopantzev, H.E. Waldenmaier, A.G. Oliveira, Y. Oba, E. Barsova,
E.A. Bogdanova, T. Gabaldón, C.V. Stevani, S. Lukyanov, I.V. Smirnov, J.I. Gitelson,
F. Kondrashov, I.V. Yampolsky, Proceedings of the National Academy of Sciences
of the United States of America 115 (2018) 12728–12732.
date_created: 2018-12-23T22:59:18Z
date_published: 2018-12-11T00:00:00Z
date_updated: 2023-09-11T14:04:05Z
day: '11'
ddc:
- '580'
department:
- _id: FyKo
doi: 10.1073/pnas.1803615115
external_id:
isi:
- '000452866000068'
file:
- access_level: open_access
checksum: 46b2c12185eb2ddb598f4c7b4bd267bf
content_type: application/pdf
creator: dernst
date_created: 2019-02-05T15:21:40Z
date_updated: 2020-07-14T12:47:11Z
file_id: '5926'
file_name: 2018_PNAS_Kotlobay.pdf
file_size: 1271988
relation: main_file
file_date_updated: 2020-07-14T12:47:11Z
has_accepted_license: '1'
intvolume: ' 115'
isi: 1
issue: '50'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '12'
oa: 1
oa_version: Published Version
page: 12728-12732
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
issn:
- '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: Genetically encodable bioluminescent system from fungi
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 115
year: '2018'
...
---
_id: '850'
abstract:
- lang: eng
text: Fitness landscapes depict how genotypes manifest at the phenotypic level and
form the basis of our understanding of many areas of biology, yet their properties
remain elusive. Previous studies have analysed specific genes, often using their
function as a proxy for fitness, experimentally assessing the effect on function
of single mutations and their combinations in a specific sequence or in different
sequences. However, systematic high-throughput studies of the local fitness landscape
of an entire protein have not yet been reported. Here we visualize an extensive
region of the local fitness landscape of the green fluorescent protein from Aequorea
Victoria (avGFP) by measuring the native function (fluorescence) of tens of thousands
of derivative genotypes of avGFP. We show that the fitness landscape of avGFP
is narrow, with 3/4 of the derivatives with a single mutation showing reduced
fluorescence and half of the derivatives with four mutations being completely
non-fluorescent. The narrowness is enhanced by epistasis, which was detected in
up to 30% of genotypes with multiple mutations and mostly occurred through the
cumulative effect of slightly deleterious mutations causing a threshold-like decrease
in protein stability and a concomitant loss of fluorescence. A model of orthologous
sequence divergence spanning hundreds of millions of years predicted the extent
of epistasis in our data, indicating congruence between the fitness landscape
properties at the local and global scales. The characterization of the local fitness
landscape of avGFP has important implications for several fields including molecular
evolution, population genetics and protein design.
acknowledgement: We thank Y. Kulikova and G. Filion for discussion on statistical
analysis and I. Osterman, R. Moretti and J. Meiler for technical assistance and
M. Friesen for a critical reading of the manuscript. We thank H. Himmelbauer, CRG
Genomic Unit and the Russian Science Foundation project (14-50-00150) for sequencing.
Experiments were partially carried out using the equipment provided by the IBCH
core facility (CKP IBCH). The work was supported by HHMI International Early Career
Scientist Program (55007424), the EMBO Young Investigator Programme, MINECO (BFU2012-31329),
Spanish Ministry of Economy and Competitiveness Centro de Excelencia Severo Ochoa
2013-2017 grant (SEV-2012-0208), Secretaria d'Universitats i Recerca del Departament
d'Economia i Coneixement de la Generalitat's AGAUR program (2014 SGR 0974), Russian
Science Foundation (14-25-00129) and the European Research Council under the European
Union's Seventh Framework Programme (FP7/2007-2013, ERC grant agreement, 335980-EinME).
author:
- first_name: Karen
full_name: Karen Sarkisyan
id: 39A7BF80-F248-11E8-B48F-1D18A9856A87
last_name: Sarkisyan
orcid: 0000-0002-5375-6341
- first_name: Dmitry
full_name: Bolotin, Dmitry A
last_name: Bolotin
- first_name: Margarita
full_name: Meer, Margarita V
last_name: Meer
- first_name: Dinara
full_name: Usmanova, Dinara R
last_name: Usmanova
- first_name: Alexander
full_name: Mishin, Alexander S
last_name: Mishin
- first_name: George
full_name: Sharonov, George V
last_name: Sharonov
- first_name: Dmitry
full_name: Ivankov, Dmitry N
last_name: Ivankov
- first_name: Nina
full_name: Bozhanova, Nina G
last_name: Bozhanova
- first_name: Mikhail
full_name: Baranov, Mikhail S
last_name: Baranov
- first_name: Onuralp
full_name: Soylemez, Onuralp
last_name: Soylemez
- first_name: Natalya
full_name: Bogatyreva, Natalya S
last_name: Bogatyreva
- first_name: Peter
full_name: Vlasov, Peter K
last_name: Vlasov
- first_name: Evgeny
full_name: Egorov, Evgeny S
last_name: Egorov
- first_name: Maria
full_name: Logacheva, Maria D
last_name: Logacheva
- first_name: Alexey
full_name: Kondrashov, Alexey S
last_name: Kondrashov
- first_name: Dmitriy
full_name: Chudakov, Dmitriy M
last_name: Chudakov
- first_name: Ekaterina
full_name: Putintseva, Ekaterina V
last_name: Putintseva
- first_name: Ilgar
full_name: Mamedov, Ilgar Z
last_name: Mamedov
- first_name: Dan
full_name: Tawfik, Dan S
last_name: Tawfik
- first_name: Konstantin
full_name: Lukyanov, Konstantin A
last_name: Lukyanov
- first_name: Fyodor
full_name: Fyodor Kondrashov
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
citation:
ama: Sarkisyan K, Bolotin D, Meer M, et al. Local fitness landscape of the green
fluorescent protein. Nature. 2016;533:397-401. doi:10.1038/nature17995
apa: Sarkisyan, K., Bolotin, D., Meer, M., Usmanova, D., Mishin, A., Sharonov, G.,
… Kondrashov, F. (2016). Local fitness landscape of the green fluorescent protein.
Nature. Nature Publishing Group. https://doi.org/10.1038/nature17995
chicago: Sarkisyan, Karen, Dmitry Bolotin, Margarita Meer, Dinara Usmanova, Alexander
Mishin, George Sharonov, Dmitry Ivankov, et al. “Local Fitness Landscape of the
Green Fluorescent Protein.” Nature. Nature Publishing Group, 2016. https://doi.org/10.1038/nature17995.
ieee: K. Sarkisyan et al., “Local fitness landscape of the green fluorescent
protein,” Nature, vol. 533. Nature Publishing Group, pp. 397–401, 2016.
ista: Sarkisyan K, Bolotin D, Meer M, Usmanova D, Mishin A, Sharonov G, Ivankov
D, Bozhanova N, Baranov M, Soylemez O, Bogatyreva N, Vlasov P, Egorov E, Logacheva
M, Kondrashov A, Chudakov D, Putintseva E, Mamedov I, Tawfik D, Lukyanov K, Kondrashov
F. 2016. Local fitness landscape of the green fluorescent protein. Nature. 533,
397–401.
mla: Sarkisyan, Karen, et al. “Local Fitness Landscape of the Green Fluorescent
Protein.” Nature, vol. 533, Nature Publishing Group, 2016, pp. 397–401,
doi:10.1038/nature17995.
short: K. Sarkisyan, D. Bolotin, M. Meer, D. Usmanova, A. Mishin, G. Sharonov, D.
Ivankov, N. Bozhanova, M. Baranov, O. Soylemez, N. Bogatyreva, P. Vlasov, E. Egorov,
M. Logacheva, A. Kondrashov, D. Chudakov, E. Putintseva, I. Mamedov, D. Tawfik,
K. Lukyanov, F. Kondrashov, Nature 533 (2016) 397–401.
date_created: 2018-12-11T11:48:50Z
date_published: 2016-05-11T00:00:00Z
date_updated: 2021-01-12T08:19:42Z
day: '11'
doi: 10.1038/nature17995
extern: 1
intvolume: ' 533'
month: '05'
page: 397 - 401
publication: Nature
publication_status: published
publisher: Nature Publishing Group
publist_id: '6799'
quality_controlled: 0
status: public
title: Local fitness landscape of the green fluorescent protein
type: journal_article
volume: 533
year: '2016'
...