The ace-1 Locus Is Amplified in All Resistant Anopheles gambiae Mosquitoes: Fitness Consequences of Homogeneous and Heterogeneous Duplications.
Gene copy-number variations are widespread in natural populations, but investigating their phenotypic consequences requires contemporary duplications under selection. Such duplications have been found at the ace-1 locus (encoding the organophosphate and carbamate insecticides' target) in the mo...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-12-01
|
| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.2000618 |
| _version_ | 1829499104364855296 |
|---|---|
| author | Benoît S Assogba Pascal Milesi Luc S Djogbénou Arnaud Berthomieu Patrick Makoundou Lamine S Baba-Moussa Anna-Sophie Fiston-Lavier Khalid Belkhir Pierrick Labbé Mylène Weill |
| author_facet | Benoît S Assogba Pascal Milesi Luc S Djogbénou Arnaud Berthomieu Patrick Makoundou Lamine S Baba-Moussa Anna-Sophie Fiston-Lavier Khalid Belkhir Pierrick Labbé Mylène Weill |
| author_sort | Benoît S Assogba |
| collection | DOAJ |
| description | Gene copy-number variations are widespread in natural populations, but investigating their phenotypic consequences requires contemporary duplications under selection. Such duplications have been found at the ace-1 locus (encoding the organophosphate and carbamate insecticides' target) in the mosquito Anopheles gambiae (the major malaria vector); recent studies have revealed their intriguing complexity, consistent with the involvement of various numbers and types (susceptible or resistant to insecticide) of copies. We used an integrative approach, from genome to phenotype level, to investigate the influence of duplication architecture and gene-dosage on mosquito fitness. We found that both heterogeneous (i.e., one susceptible and one resistant ace-1 copy) and homogeneous (i.e., identical resistant copies) duplications segregated in field populations. The number of copies in homogeneous duplications was variable and positively correlated with acetylcholinesterase activity and resistance level. Determining the genomic structure of the duplicated region revealed that, in both types of duplication, ace-1 and 11 other genes formed tandem 203kb amplicons. We developed a diagnostic test for duplications, which showed that ace-1 was amplified in all 173 resistant mosquitoes analyzed (field-collected in several African countries), in heterogeneous or homogeneous duplications. Each type was associated with different fitness trade-offs: heterogeneous duplications conferred an intermediate phenotype (lower resistance and fitness costs), whereas homogeneous duplications tended to increase both resistance and fitness cost, in a complex manner. The type of duplication selected seemed thus to depend on the intensity and distribution of selection pressures. This versatility of trade-offs available through gene duplication highlights the importance of large mutation events in adaptation to environmental variation. This impressive adaptability could have a major impact on vector control in Africa. |
| first_indexed | 2024-12-16T08:27:01Z |
| format | Article |
| id | doaj.art-a77ffa43a74043fcac8256de77632ef4 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-16T08:27:01Z |
| publishDate | 2016-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-a77ffa43a74043fcac8256de77632ef42022-12-21T22:37:58ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852016-12-011412e200061810.1371/journal.pbio.2000618The ace-1 Locus Is Amplified in All Resistant Anopheles gambiae Mosquitoes: Fitness Consequences of Homogeneous and Heterogeneous Duplications.Benoît S AssogbaPascal MilesiLuc S DjogbénouArnaud BerthomieuPatrick MakoundouLamine S Baba-MoussaAnna-Sophie Fiston-LavierKhalid BelkhirPierrick LabbéMylène WeillGene copy-number variations are widespread in natural populations, but investigating their phenotypic consequences requires contemporary duplications under selection. Such duplications have been found at the ace-1 locus (encoding the organophosphate and carbamate insecticides' target) in the mosquito Anopheles gambiae (the major malaria vector); recent studies have revealed their intriguing complexity, consistent with the involvement of various numbers and types (susceptible or resistant to insecticide) of copies. We used an integrative approach, from genome to phenotype level, to investigate the influence of duplication architecture and gene-dosage on mosquito fitness. We found that both heterogeneous (i.e., one susceptible and one resistant ace-1 copy) and homogeneous (i.e., identical resistant copies) duplications segregated in field populations. The number of copies in homogeneous duplications was variable and positively correlated with acetylcholinesterase activity and resistance level. Determining the genomic structure of the duplicated region revealed that, in both types of duplication, ace-1 and 11 other genes formed tandem 203kb amplicons. We developed a diagnostic test for duplications, which showed that ace-1 was amplified in all 173 resistant mosquitoes analyzed (field-collected in several African countries), in heterogeneous or homogeneous duplications. Each type was associated with different fitness trade-offs: heterogeneous duplications conferred an intermediate phenotype (lower resistance and fitness costs), whereas homogeneous duplications tended to increase both resistance and fitness cost, in a complex manner. The type of duplication selected seemed thus to depend on the intensity and distribution of selection pressures. This versatility of trade-offs available through gene duplication highlights the importance of large mutation events in adaptation to environmental variation. This impressive adaptability could have a major impact on vector control in Africa.https://doi.org/10.1371/journal.pbio.2000618 |
| spellingShingle | Benoît S Assogba Pascal Milesi Luc S Djogbénou Arnaud Berthomieu Patrick Makoundou Lamine S Baba-Moussa Anna-Sophie Fiston-Lavier Khalid Belkhir Pierrick Labbé Mylène Weill The ace-1 Locus Is Amplified in All Resistant Anopheles gambiae Mosquitoes: Fitness Consequences of Homogeneous and Heterogeneous Duplications. PLoS Biology |
| title | The ace-1 Locus Is Amplified in All Resistant Anopheles gambiae Mosquitoes: Fitness Consequences of Homogeneous and Heterogeneous Duplications. |
| title_full | The ace-1 Locus Is Amplified in All Resistant Anopheles gambiae Mosquitoes: Fitness Consequences of Homogeneous and Heterogeneous Duplications. |
| title_fullStr | The ace-1 Locus Is Amplified in All Resistant Anopheles gambiae Mosquitoes: Fitness Consequences of Homogeneous and Heterogeneous Duplications. |
| title_full_unstemmed | The ace-1 Locus Is Amplified in All Resistant Anopheles gambiae Mosquitoes: Fitness Consequences of Homogeneous and Heterogeneous Duplications. |
| title_short | The ace-1 Locus Is Amplified in All Resistant Anopheles gambiae Mosquitoes: Fitness Consequences of Homogeneous and Heterogeneous Duplications. |
| title_sort | ace 1 locus is amplified in all resistant anopheles gambiae mosquitoes fitness consequences of homogeneous and heterogeneous duplications |
| url | https://doi.org/10.1371/journal.pbio.2000618 |
| work_keys_str_mv | AT benoitsassogba theace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT pascalmilesi theace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT lucsdjogbenou theace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT arnaudberthomieu theace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT patrickmakoundou theace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT laminesbabamoussa theace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT annasophiefistonlavier theace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT khalidbelkhir theace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT pierricklabbe theace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT myleneweill theace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT benoitsassogba ace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT pascalmilesi ace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT lucsdjogbenou ace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT arnaudberthomieu ace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT patrickmakoundou ace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT laminesbabamoussa ace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT annasophiefistonlavier ace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT khalidbelkhir ace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT pierricklabbe ace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications AT myleneweill ace1locusisamplifiedinallresistantanophelesgambiaemosquitoesfitnessconsequencesofhomogeneousandheterogeneousduplications |