GEPHE SUMMARY Print
Entry Status
Published
GepheID
GP00001964
Main curator
Courtier
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Drosophila orena - lower enzyme activity
Trait State in Taxon B
Drosophila erecta - higher enzyme activity
Ancestral State
Unknown
Taxonomic Status
Taxon A
Common Name
-
Synonyms
-
Rank
species
Lineage
Show more ... Brachycera; Muscomorpha; Eremoneura; Cyclorrhapha; Schizophora; Acalyptratae; Ephydroidea; Drosophilidae; Drosophilinae; Drosophilini; Drosophila; Sophophora; melanogaster group; melanogaster subgroup
NCBI Taxonomy ID
is Taxon A an Infraspecies?
No
Taxon B
Common Name
-
Synonyms
-
Rank
species
Lineage
Show more ... Brachycera; Muscomorpha; Eremoneura; Cyclorrhapha; Schizophora; Acalyptratae; Ephydroidea; Drosophilidae; Drosophilinae; Drosophilini; Drosophila; Sophophora; melanogaster group; melanogaster subgroup
NCBI Taxonomy ID
is Taxon B an Infraspecies?
No
GENOTYPIC CHANGE
Mutation #1
Presumptive Null
No
Molecular Type
Aberration Type
SNP
SNP Coding Change
Nonsynonymous
Molecular Details of the Mutation
In vitro assay by replacement of the entire coding region. Four possible amino acid changes. Exact causal amino acid change(s) not identified.
Experimental Evidence
Taxon A Taxon B Position
Codon - - -
Amino-acid - - -
Authors
Loehlin DW; Ames JR; Vaccaro K; Carroll SB
Abstract
The quantitative evolution of protein activity is a common phenomenon, yet we know little about any general mechanistic tendencies that underlie it. For example, an increase (or decrease) in enzyme activity may evolve from changes in protein sequence that alter specific activity, or from changes in gene expression that alter the amount of protein produced. The latter in turn could arise via mutations that affect gene transcription, posttranscriptional processes, or copy number. Here, to determine the types of genetic changes underlying the quantitative evolution of protein activity, we dissected the basis of ecologically relevant differences in Alcohol dehydrogenase (Adh) enzyme activity between and within several Drosophila species. By using recombinant Adh transgenes to map the functional divergence of ADH enzyme activity in vivo, we find that amino acid substitutions explain only a minority (0 to 25%) of between- and within-species differences in enzyme activity. Instead, noncoding substitutions that occur across many parts of the gene (enhancer, promoter, and 5' and 3' untranslated regions) account for the majority of activity differences. Surprisingly, one substitution in a transcriptional Initiator element has occurred in parallel in two species, indicating that core promoters can be an important natural source of the tuning of gene activity. Furthermore, we show that both regulatory and coding substitutions contribute to fitness (resistance to ethanol toxicity). Although qualitative changes in protein specificity necessarily derive from coding mutations, these results suggest that regulatory mutations may be the primary source of quantitative changes in protein activity, a possibility overlooked in most analyses of protein evolution.

Copyright © 2019 the Author(s). Published by PNAS.
Additional References
Mutation #2
Presumptive Null
No
Molecular Type
Aberration Type
Molecular Details of the Mutation
5' flanking region. Exact mutation(s) not identified.
Experimental Evidence
Authors
Loehlin DW; Ames JR; Vaccaro K; Carroll SB
Abstract
The quantitative evolution of protein activity is a common phenomenon, yet we know little about any general mechanistic tendencies that underlie it. For example, an increase (or decrease) in enzyme activity may evolve from changes in protein sequence that alter specific activity, or from changes in gene expression that alter the amount of protein produced. The latter in turn could arise via mutations that affect gene transcription, posttranscriptional processes, or copy number. Here, to determine the types of genetic changes underlying the quantitative evolution of protein activity, we dissected the basis of ecologically relevant differences in Alcohol dehydrogenase (Adh) enzyme activity between and within several Drosophila species. By using recombinant Adh transgenes to map the functional divergence of ADH enzyme activity in vivo, we find that amino acid substitutions explain only a minority (0 to 25%) of between- and within-species differences in enzyme activity. Instead, noncoding substitutions that occur across many parts of the gene (enhancer, promoter, and 5' and 3' untranslated regions) account for the majority of activity differences. Surprisingly, one substitution in a transcriptional Initiator element has occurred in parallel in two species, indicating that core promoters can be an important natural source of the tuning of gene activity. Furthermore, we show that both regulatory and coding substitutions contribute to fitness (resistance to ethanol toxicity). Although qualitative changes in protein specificity necessarily derive from coding mutations, these results suggest that regulatory mutations may be the primary source of quantitative changes in protein activity, a possibility overlooked in most analyses of protein evolution.

Copyright © 2019 the Author(s). Published by PNAS.
Additional References
Mutation #3
Presumptive Null
No
Molecular Type
Aberration Type
Molecular Details of the Mutation
5' UTR region. Exact mutation(s) not identified.
Experimental Evidence
Authors
Loehlin DW; Ames JR; Vaccaro K; Carroll SB
Abstract
The quantitative evolution of protein activity is a common phenomenon, yet we know little about any general mechanistic tendencies that underlie it. For example, an increase (or decrease) in enzyme activity may evolve from changes in protein sequence that alter specific activity, or from changes in gene expression that alter the amount of protein produced. The latter in turn could arise via mutations that affect gene transcription, posttranscriptional processes, or copy number. Here, to determine the types of genetic changes underlying the quantitative evolution of protein activity, we dissected the basis of ecologically relevant differences in Alcohol dehydrogenase (Adh) enzyme activity between and within several Drosophila species. By using recombinant Adh transgenes to map the functional divergence of ADH enzyme activity in vivo, we find that amino acid substitutions explain only a minority (0 to 25%) of between- and within-species differences in enzyme activity. Instead, noncoding substitutions that occur across many parts of the gene (enhancer, promoter, and 5' and 3' untranslated regions) account for the majority of activity differences. Surprisingly, one substitution in a transcriptional Initiator element has occurred in parallel in two species, indicating that core promoters can be an important natural source of the tuning of gene activity. Furthermore, we show that both regulatory and coding substitutions contribute to fitness (resistance to ethanol toxicity). Although qualitative changes in protein specificity necessarily derive from coding mutations, these results suggest that regulatory mutations may be the primary source of quantitative changes in protein activity, a possibility overlooked in most analyses of protein evolution.

Copyright © 2019 the Author(s). Published by PNAS.
Additional References
Mutation #4
Presumptive Null
No
Molecular Type
Aberration Type
Molecular Details of the Mutation
3' UTR region. Exact mutation(s) not identified. Effect on Ads activity in the opposite direction compared to the other Adh regions.
Experimental Evidence
Authors
Loehlin DW; Ames JR; Vaccaro K; Carroll SB
Abstract
The quantitative evolution of protein activity is a common phenomenon, yet we know little about any general mechanistic tendencies that underlie it. For example, an increase (or decrease) in enzyme activity may evolve from changes in protein sequence that alter specific activity, or from changes in gene expression that alter the amount of protein produced. The latter in turn could arise via mutations that affect gene transcription, posttranscriptional processes, or copy number. Here, to determine the types of genetic changes underlying the quantitative evolution of protein activity, we dissected the basis of ecologically relevant differences in Alcohol dehydrogenase (Adh) enzyme activity between and within several Drosophila species. By using recombinant Adh transgenes to map the functional divergence of ADH enzyme activity in vivo, we find that amino acid substitutions explain only a minority (0 to 25%) of between- and within-species differences in enzyme activity. Instead, noncoding substitutions that occur across many parts of the gene (enhancer, promoter, and 5' and 3' untranslated regions) account for the majority of activity differences. Surprisingly, one substitution in a transcriptional Initiator element has occurred in parallel in two species, indicating that core promoters can be an important natural source of the tuning of gene activity. Furthermore, we show that both regulatory and coding substitutions contribute to fitness (resistance to ethanol toxicity). Although qualitative changes in protein specificity necessarily derive from coding mutations, these results suggest that regulatory mutations may be the primary source of quantitative changes in protein activity, a possibility overlooked in most analyses of protein evolution.

Copyright © 2019 the Author(s). Published by PNAS.
Additional References
RELATED GEPHE
Related Genes
No matches found.
Related Haplotypes
No matches found.
EXTERNAL LINKS
COMMENTS
@SeveralMutationsWithEffect - There is a consensus phenotype of moderate ADH activity in the broader taxonomic group (Mercot et al. 1994). With the transformed alleles David Loehlin also observed "moderate" activity in mel-slow; D. erecta and D. yakuba. This suggests that D. santomea and D. orena have derived low phenotypes but the phylogenetic signal is weak. - Entry validated by David Loehlin
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