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Snake venoms are integrated systems, but abundant venom proteins evolve more rapidly.

Aird SD, Aggarwal S, Villar-Briones A, Tin MM, Terada K, Mikheyev AS - BMC Genomics (2015)

Bottom Line: Hybrids produced most proteins found in both parental venoms.Given log-scale differences in toxin abundance, which are likely correlated with biosynthetic costs, we hypothesize that as a result of natural selection, snakes optimize return on energetic investment by producing more of venom proteins that increase their fitness.Adaptive evolution of venoms may occur most rapidly through changes in expression levels that alter fitness contributions, and thus the strength of selection acting on specific secretome components.

View Article: PubMed Central - PubMed

Affiliation: Okinawa Institute of Science and Technology Graduate University, Tancha 1919-1, Onna-son, Kunigami-gun, Okinawa-ken, 904-0412, Japan. steven.aird@oist.jp.

ABSTRACT

Background: While many studies have shown that extracellular proteins evolve rapidly, how selection acts on them remains poorly understood. We used snake venoms to understand the interaction between ecology, expression level, and evolutionary rate in secreted protein systems. Venomous snakes employ well-integrated systems of proteins and organic constituents to immobilize prey. Venoms are generally optimized to subdue preferred prey more effectively than non-prey, and many venom protein families manifest positive selection and rapid gene family diversification. Although previous studies have illuminated how individual venom protein families evolve, how selection acts on venoms as integrated systems, is unknown.

Results: Using next-generation transcriptome sequencing and mass spectrometry, we examined microevolution in two pitvipers, allopatrically separated for at least 1.6 million years, and their hybrids. Transcriptomes of parental species had generally similar compositions in regard to protein families, but for a given protein family, the homologs present and concentrations thereof sometimes differed dramatically. For instance, a phospholipase A2 transcript comprising 73.4 % of the Protobothrops elegans transcriptome, was barely present in the P. flavoviridis transcriptome (<0.05 %). Hybrids produced most proteins found in both parental venoms. Protein evolutionary rates were positively correlated with transcriptomic and proteomic abundances, and the most abundant proteins showed positive selection. This pattern holds with the addition of four other published crotaline transcriptomes, from two more genera, and also for the recently published king cobra genome, suggesting that rapid evolution of abundant proteins may be generally true for snake venoms. Looking more broadly at Protobothrops, we show that rapid evolution of the most abundant components is due to positive selection, suggesting an interplay between abundance and adaptation.

Conclusions: Given log-scale differences in toxin abundance, which are likely correlated with biosynthetic costs, we hypothesize that as a result of natural selection, snakes optimize return on energetic investment by producing more of venom proteins that increase their fitness. Natural selection then acts on the additive genetic variance of these components, in proportion to their contributions to overall fitness. Adaptive evolution of venoms may occur most rapidly through changes in expression levels that alter fitness contributions, and thus the strength of selection acting on specific secretome components.

No MeSH data available.


Protobothrops flavoviridis x P. elegans hybrids express phospholipases A2 from both parental venoms. a Aligned PLA2 transcripts from P. flavoviridis and P. elegans transcriptomes. The solid heavy vertical line separates the signal peptides from the expressed PLA2s. A noncatalytic, myotoxic PLA2 transcript (comp43_c0_seq1) from P. elegans specimen #3 accounted for 73.4 % of all P. elegans transcripts (Additional file 2: Table S1). This protein was heavily expressed in all three specimens and in both hybrids (Fig 3). A homologous transcript was found in the transcriptome of P. flavoviridis specimen #3, but it constituted less than 0.05 % of all P. flavoviridis transcripts (Additional file 3: Table S2). No peptides from this myotoxic PLA2 transcript were detected in venoms of any P. flavoviridis specimens, or of the hybrids (Fig 3). P. elegans transcript comp47_c0_seq1 is homologous to P. flavoviridis transcript comp41_c0_seq1 (Fig 3). P. elegans specimens expressed the PLA2 corresponding to the former transcript, while P. flavoviridis specimens expressed the latter. Hybrids expressed both (Fig 3; Additional file 8: Figure S5). The P. flavoviridis transcriptome also contained two additional PLA2 trancripts, comp40_c0_seq1 and comp48_c0_seq1 (Additional file 3: Table S2). These had no homologs in the P. elegans transcriptome, but hybrids produced both of these, as did all three P. flavoviridis specimens (Fig 3; Additional file 8: Figure S5). b Peptide coverage of venom PLA2 transcripts is similar between hybrids and non-hybrid specimens. Peptides from P. elegans venoms are indicated by green bars above the sequences, while those from P. flavoviridis venoms are in blue and those of hybrids are in gray. For any given transcript, peptides were sequenced from essentially the same portions of the PLA2 in both hybrid and non-hybrid venoms
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Fig2: Protobothrops flavoviridis x P. elegans hybrids express phospholipases A2 from both parental venoms. a Aligned PLA2 transcripts from P. flavoviridis and P. elegans transcriptomes. The solid heavy vertical line separates the signal peptides from the expressed PLA2s. A noncatalytic, myotoxic PLA2 transcript (comp43_c0_seq1) from P. elegans specimen #3 accounted for 73.4 % of all P. elegans transcripts (Additional file 2: Table S1). This protein was heavily expressed in all three specimens and in both hybrids (Fig 3). A homologous transcript was found in the transcriptome of P. flavoviridis specimen #3, but it constituted less than 0.05 % of all P. flavoviridis transcripts (Additional file 3: Table S2). No peptides from this myotoxic PLA2 transcript were detected in venoms of any P. flavoviridis specimens, or of the hybrids (Fig 3). P. elegans transcript comp47_c0_seq1 is homologous to P. flavoviridis transcript comp41_c0_seq1 (Fig 3). P. elegans specimens expressed the PLA2 corresponding to the former transcript, while P. flavoviridis specimens expressed the latter. Hybrids expressed both (Fig 3; Additional file 8: Figure S5). The P. flavoviridis transcriptome also contained two additional PLA2 trancripts, comp40_c0_seq1 and comp48_c0_seq1 (Additional file 3: Table S2). These had no homologs in the P. elegans transcriptome, but hybrids produced both of these, as did all three P. flavoviridis specimens (Fig 3; Additional file 8: Figure S5). b Peptide coverage of venom PLA2 transcripts is similar between hybrids and non-hybrid specimens. Peptides from P. elegans venoms are indicated by green bars above the sequences, while those from P. flavoviridis venoms are in blue and those of hybrids are in gray. For any given transcript, peptides were sequenced from essentially the same portions of the PLA2 in both hybrid and non-hybrid venoms

Mentions: Based on homology to other PLA2s of known pharmacology, P. elegans transcript comp43_c0_seq1 that constituted 73.4 % of all transcripts, encodes a noncatalytic, myotoxic PLA2 myotoxin that shows considerable homology to other Asian crotaline myotoxins (Fig. 2a; Additional file 4: Figure S1A; Additional file 5: Figure S3; Additional file 2: Table S1). In contrast, while P. flavoviridis also has a transcript (Pf_comp552_c0_seq1) for a homologous, non-catalytic, myotoxic PLA2, this transcript represents <0.05 % of the latter transcriptome. Both the P. elegans and P. flavoviridis myotoxins have an arginine residue (position 48) where catalytic PLA2s have aspartic acid in order to bind the Ca2+ ion required for catalysis. Many New World crotalines have lysine in this position. All three P. elegans specimens and the two hybrids express Pe_comp43_c0_seq1 heavily, but no snakes in this study produced the P. flavoviridis homolog, Pf comp552_c0_seq1 (Fig 3; Fig. 2; Additional file 6: Figure S5).Fig. 2


Snake venoms are integrated systems, but abundant venom proteins evolve more rapidly.

Aird SD, Aggarwal S, Villar-Briones A, Tin MM, Terada K, Mikheyev AS - BMC Genomics (2015)

Protobothrops flavoviridis x P. elegans hybrids express phospholipases A2 from both parental venoms. a Aligned PLA2 transcripts from P. flavoviridis and P. elegans transcriptomes. The solid heavy vertical line separates the signal peptides from the expressed PLA2s. A noncatalytic, myotoxic PLA2 transcript (comp43_c0_seq1) from P. elegans specimen #3 accounted for 73.4 % of all P. elegans transcripts (Additional file 2: Table S1). This protein was heavily expressed in all three specimens and in both hybrids (Fig 3). A homologous transcript was found in the transcriptome of P. flavoviridis specimen #3, but it constituted less than 0.05 % of all P. flavoviridis transcripts (Additional file 3: Table S2). No peptides from this myotoxic PLA2 transcript were detected in venoms of any P. flavoviridis specimens, or of the hybrids (Fig 3). P. elegans transcript comp47_c0_seq1 is homologous to P. flavoviridis transcript comp41_c0_seq1 (Fig 3). P. elegans specimens expressed the PLA2 corresponding to the former transcript, while P. flavoviridis specimens expressed the latter. Hybrids expressed both (Fig 3; Additional file 8: Figure S5). The P. flavoviridis transcriptome also contained two additional PLA2 trancripts, comp40_c0_seq1 and comp48_c0_seq1 (Additional file 3: Table S2). These had no homologs in the P. elegans transcriptome, but hybrids produced both of these, as did all three P. flavoviridis specimens (Fig 3; Additional file 8: Figure S5). b Peptide coverage of venom PLA2 transcripts is similar between hybrids and non-hybrid specimens. Peptides from P. elegans venoms are indicated by green bars above the sequences, while those from P. flavoviridis venoms are in blue and those of hybrids are in gray. For any given transcript, peptides were sequenced from essentially the same portions of the PLA2 in both hybrid and non-hybrid venoms
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Related In: Results  -  Collection

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Fig2: Protobothrops flavoviridis x P. elegans hybrids express phospholipases A2 from both parental venoms. a Aligned PLA2 transcripts from P. flavoviridis and P. elegans transcriptomes. The solid heavy vertical line separates the signal peptides from the expressed PLA2s. A noncatalytic, myotoxic PLA2 transcript (comp43_c0_seq1) from P. elegans specimen #3 accounted for 73.4 % of all P. elegans transcripts (Additional file 2: Table S1). This protein was heavily expressed in all three specimens and in both hybrids (Fig 3). A homologous transcript was found in the transcriptome of P. flavoviridis specimen #3, but it constituted less than 0.05 % of all P. flavoviridis transcripts (Additional file 3: Table S2). No peptides from this myotoxic PLA2 transcript were detected in venoms of any P. flavoviridis specimens, or of the hybrids (Fig 3). P. elegans transcript comp47_c0_seq1 is homologous to P. flavoviridis transcript comp41_c0_seq1 (Fig 3). P. elegans specimens expressed the PLA2 corresponding to the former transcript, while P. flavoviridis specimens expressed the latter. Hybrids expressed both (Fig 3; Additional file 8: Figure S5). The P. flavoviridis transcriptome also contained two additional PLA2 trancripts, comp40_c0_seq1 and comp48_c0_seq1 (Additional file 3: Table S2). These had no homologs in the P. elegans transcriptome, but hybrids produced both of these, as did all three P. flavoviridis specimens (Fig 3; Additional file 8: Figure S5). b Peptide coverage of venom PLA2 transcripts is similar between hybrids and non-hybrid specimens. Peptides from P. elegans venoms are indicated by green bars above the sequences, while those from P. flavoviridis venoms are in blue and those of hybrids are in gray. For any given transcript, peptides were sequenced from essentially the same portions of the PLA2 in both hybrid and non-hybrid venoms
Mentions: Based on homology to other PLA2s of known pharmacology, P. elegans transcript comp43_c0_seq1 that constituted 73.4 % of all transcripts, encodes a noncatalytic, myotoxic PLA2 myotoxin that shows considerable homology to other Asian crotaline myotoxins (Fig. 2a; Additional file 4: Figure S1A; Additional file 5: Figure S3; Additional file 2: Table S1). In contrast, while P. flavoviridis also has a transcript (Pf_comp552_c0_seq1) for a homologous, non-catalytic, myotoxic PLA2, this transcript represents <0.05 % of the latter transcriptome. Both the P. elegans and P. flavoviridis myotoxins have an arginine residue (position 48) where catalytic PLA2s have aspartic acid in order to bind the Ca2+ ion required for catalysis. Many New World crotalines have lysine in this position. All three P. elegans specimens and the two hybrids express Pe_comp43_c0_seq1 heavily, but no snakes in this study produced the P. flavoviridis homolog, Pf comp552_c0_seq1 (Fig 3; Fig. 2; Additional file 6: Figure S5).Fig. 2

Bottom Line: Hybrids produced most proteins found in both parental venoms.Given log-scale differences in toxin abundance, which are likely correlated with biosynthetic costs, we hypothesize that as a result of natural selection, snakes optimize return on energetic investment by producing more of venom proteins that increase their fitness.Adaptive evolution of venoms may occur most rapidly through changes in expression levels that alter fitness contributions, and thus the strength of selection acting on specific secretome components.

View Article: PubMed Central - PubMed

Affiliation: Okinawa Institute of Science and Technology Graduate University, Tancha 1919-1, Onna-son, Kunigami-gun, Okinawa-ken, 904-0412, Japan. steven.aird@oist.jp.

ABSTRACT

Background: While many studies have shown that extracellular proteins evolve rapidly, how selection acts on them remains poorly understood. We used snake venoms to understand the interaction between ecology, expression level, and evolutionary rate in secreted protein systems. Venomous snakes employ well-integrated systems of proteins and organic constituents to immobilize prey. Venoms are generally optimized to subdue preferred prey more effectively than non-prey, and many venom protein families manifest positive selection and rapid gene family diversification. Although previous studies have illuminated how individual venom protein families evolve, how selection acts on venoms as integrated systems, is unknown.

Results: Using next-generation transcriptome sequencing and mass spectrometry, we examined microevolution in two pitvipers, allopatrically separated for at least 1.6 million years, and their hybrids. Transcriptomes of parental species had generally similar compositions in regard to protein families, but for a given protein family, the homologs present and concentrations thereof sometimes differed dramatically. For instance, a phospholipase A2 transcript comprising 73.4 % of the Protobothrops elegans transcriptome, was barely present in the P. flavoviridis transcriptome (<0.05 %). Hybrids produced most proteins found in both parental venoms. Protein evolutionary rates were positively correlated with transcriptomic and proteomic abundances, and the most abundant proteins showed positive selection. This pattern holds with the addition of four other published crotaline transcriptomes, from two more genera, and also for the recently published king cobra genome, suggesting that rapid evolution of abundant proteins may be generally true for snake venoms. Looking more broadly at Protobothrops, we show that rapid evolution of the most abundant components is due to positive selection, suggesting an interplay between abundance and adaptation.

Conclusions: Given log-scale differences in toxin abundance, which are likely correlated with biosynthetic costs, we hypothesize that as a result of natural selection, snakes optimize return on energetic investment by producing more of venom proteins that increase their fitness. Natural selection then acts on the additive genetic variance of these components, in proportion to their contributions to overall fitness. Adaptive evolution of venoms may occur most rapidly through changes in expression levels that alter fitness contributions, and thus the strength of selection acting on specific secretome components.

No MeSH data available.