Contains four supplementary tables and eight supplementary figures. (PDF 1474 kb)
Research Interests:
BackgroundMost organisms rely on a molecular circadian clock to orchestrate a wide range of physiological processes to match the 24-hour day. These molecular clocks are typically based on a negative feedback loop among a small set of... more
BackgroundMost organisms rely on a molecular circadian clock to orchestrate a wide range of physiological processes to match the 24-hour day. These molecular clocks are typically based on a negative feedback loop among a small set of proteins that govern the circadian output. Light or other environmental conditions can reset the circadian clock, but true circadian behaviors continue to cycle even in constant darkness, with an intrinsic period called the free-running period (FRP). Spiders have unusual FRPs, with some species having extremely short FRP (e.g. 18 hours for trashline orb weaver), and many having highly variable FRPs (intraspecific variation of up to 10 hours). In the absence of any genetic model of circadian rhythms in spiders, we developed a mathematical model to optimize experimental conditions for identifying circadian genes that also respond to light cues. ResultsOur mathematical model involved a single gene that encodes a protein that inhibits its own transcription....
Research Interests:
Research Interests: Bioinformatics, Evolutionary Biology, Genetics, Genomics, Computational Biology, and 15 moreMolecular Evolution, Biology, Evolution, Medicine, Next generation sequencing, Biological Sciences, Phylogeny, Silk, Female, Animals, De Novo Genome Assembly, Gene Family, Gene expression profiling, Black widow spider, and Medical and Health Sciences
Supplementary Text and Supplementary Figures: Figures S1 – S34.
Supplementary Tables S1 – S29.
The origin of aggregate silk glands and their production of wet adhesive silks is considered a key innovation of the Araneoidea, a superfamily of spiders that build orb-webs and cobwebs. Orb-web weavers place aggregate glue on an... more
The origin of aggregate silk glands and their production of wet adhesive silks is considered a key innovation of the Araneoidea, a superfamily of spiders that build orb-webs and cobwebs. Orb-web weavers place aggregate glue on an extensible capture spiral, whereas cobweb weavers add it to the ends of strong, stiff fibers, called gumfoot lines. Here we describe the material behavior and quantitative proteomics of the aggregate glues of two cobweb weaving species, the Western black widow, Latrodectus hesperus, and the common house spider, Parasteatoda tepidariorum. For each species respectively, we identified 48 and 33 proteins that were significantly more abundant in the portion of the gumfoot line with glue than in its fibers. These proteins were more highly glycosylated and phosphorylated than proteins found in silk fibers without glue, which likely explains aggregate glue stickiness. Most glue-enriched proteins were of anterior aggregate gland origin, supporting the hypothesis tha...
Research Interests:
We examined the circadian rhythms of locomotor activity in three spider species in the Family Theridiidae under light–dark cycles and constant darkness. Contrary to previous findings in other organisms, we found exceptionally high... more
We examined the circadian rhythms of locomotor activity in three spider species in the Family Theridiidae under light–dark cycles and constant darkness. Contrary to previous findings in other organisms, we found exceptionally high variability in endogenous circadian period both within and among species. Many individuals exhibited circadian periods much lower (19–22 h) or much higher (26–30 h) than the archetypal circadian period. These results suggest relaxed selection on circadian period as well as an ability to succeed in nature despite a lack of circadian resonance with the 24-h daily cycle. Although displaying similar entrainment waveforms under light–dark cycles, there were remarkable differences among the three species with respect to levels of apparent masking and dispersion of activity under constant dark conditions. These behavioral differences suggest an aspect of chronotype adapted to the particular ecologies of the different species.
Research Interests:
Cobweb weaving spiders and their relatives spin multiple task-specific fiber types. The unique material properties of each silk type result from differences in amino acid sequence and structure of their component proteins, primarily... more
Cobweb weaving spiders and their relatives spin multiple task-specific fiber types. The unique material properties of each silk type result from differences in amino acid sequence and structure of their component proteins, primarily spidroins (spider fibrous proteins). Amino acid content and gene expression measurements of spider silks suggest some spiders change expression patterns of individual protein components in response to environmental cues. We quantified mRNA abundance of three spidroin encoding genes involved in prey capture in the common house spider,Parasteatoda tepidariorum(Theridiidae), fed different diets. After 10 days of acclimation to the lab on a diet of mealworms, spiders were split into three groups: (1) individuals were immediately dissected, (2) spiders were fed high-energy crickets, or (3) spiders were fed low-energy flies, for 1 month. All spiders gained mass during the acclimation period and cricket-fed spiders continued to gain mass, while fly-fed spiders ...
Research Interests:
Due to their abundance and ability to invade diverse environments, many arthropods have become pests of economic and health concern, especially in urban areas. Transcriptomic analyses of arthropod ovaries have provided insight into life... more
Due to their abundance and ability to invade diverse environments, many arthropods have become pests of economic and health concern, especially in urban areas. Transcriptomic analyses of arthropod ovaries have provided insight into life history variation and fecundity, yet there are few studies in spiders despite their diversity within arthropods. Here, we generated a de novo ovarian transcriptome from 10 individuals of the western black widow spider (Latrodectus hesperus), a human health pest of high abundance in urban areas, to conduct comparative ovarian transcriptomic analyses. Biological processes enriched for metabolism—specifically purine, and thiamine metabolic pathways linked to oocyte development—were significantly abundant in L. hesperus. Functional and pathway annotations revealed overlap among diverse arachnid ovarian transcriptomes for highly-conserved genes and those linked to fecundity, such as oocyte maturation in vitellogenin and vitelline membrane outer layer prot...
Research Interests:
Background Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive... more
Background Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Results Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the app...
Research Interests:
Research Interests:
Arachnids exhibit tremendous species richness and adaptations of biomedical, industrial, and agricultural importance. Yet genomic resources for arachnids are limited, with the first few spider and scorpion genomes becoming accessible in... more
Arachnids exhibit tremendous species richness and adaptations of biomedical, industrial, and agricultural importance. Yet genomic resources for arachnids are limited, with the first few spider and scorpion genomes becoming accessible in the last four years. We review key insights from these genome projects, and recommend additional genomes for sequencing, emphasizing taxa of greatest value to the scientific community. We suggest greater sampling of spiders whose genomes are understudied but hold important protein recipes for silk and venom production. We further recommend arachnid genomes to address significant evolutionary topics, including the phenotypic impact of genome duplications. A barrier to high-quality arachnid genomes are assemblies based solely on short-read data, which may be overcome by long-range sequencing and other emerging methods.
The duplication of genes can occur through various mechanisms and is thought to make a major contribution to the evolutionary diversification of organisms. There is increasing evidence for a large-scale duplication of genes in some... more
The duplication of genes can occur through various mechanisms and is thought to make a major contribution to the evolutionary diversification of organisms. There is increasing evidence for a large-scale duplication of genes in some chelicerate lineages including two rounds of whole genome duplication (WGD) in horseshoe crabs. To investigate this further, we sequenced and analyzed the genome of the common house spider Parasteatoda tepidariorum. We found pervasive duplication of both coding and non-coding genes in this spider, including two clusters of Hox genes. Analysis of synteny conservation across the P. tepidariorum genome suggests that there has been an ancient WGD in spiders. Comparison with the genomes of other chelicerates, including that of the newly sequenced bark scorpion Centruroides sculpturatus, suggests that this event occurred in the common ancestor of spiders and scorpions, and is probably independent of the WGDs in horseshoe crabs. Furthermore, characterization of ...
Research Interests:
Orb-web weaving spiders and their relatives use multiple types of task-specific silks. The majority of spider silk studies have focused on the ultra-tough dragline silk synthesized in major ampullate glands, but other silk types have... more
Orb-web weaving spiders and their relatives use multiple types of task-specific silks. The majority of spider silk studies have focused on the ultra-tough dragline silk synthesized in major ampullate glands, but other silk types have impressive material properties. For instance, minor ampullate silks of orb-web weaving spiders are as tough as draglines, due to their higher extensibility despite lower strength. Differences in material properties between silk types result from differences in their component proteins, particularly members of the spidroin (spider fibroin) gene family. However, the extent to which variation in material properties within a single silk type can be explained by variation in spidroin sequences is unknown. Here, we compare the minor ampullate spidroins (MiSp) of orb-weavers and cobweb weavers. Orb-web weavers use minor ampullate silk to form the auxiliary spiral of the orb-web while cobweb weavers use it to wrap prey, suggesting that selection pressures on mi...
Research Interests:
Intra- and interspecific relationships of 12 out of 13 described species as well as a potential new species in the spider genus Agelenopsis (Araneae: Agelenidae) were analyzed using sequence data from two mitochondrial genes, cytochrome... more
Intra- and interspecific relationships of 12 out of 13 described species as well as a potential new species in the spider genus Agelenopsis (Araneae: Agelenidae) were analyzed using sequence data from two mitochondrial genes, cytochrome oxidase I (COI) and 16S ribosomal RNA. Approximately half of the species examined formed well-supported monophyletic groups, whereas the rest of the species were part of well-supported monophyletic species groups. Rather than viewing cases where species were not identified as being monophyletic as poor taxonomy, these cases more likely represent recent speciation and offer insights into the process of speciation. The clade with the lowest levels of interspecific sequence divergence was found in eastern North America, whereas western species displayed much higher levels of interspecific divergence. These patterns appear to extend below the species level as well, with southwestern species exhibiting the highest levels of intraspecific sequence divergence and geographic structuring. The relationship between Agelenopsis and Barronopsis, a genus once considered a sub-genus of Agelenopsis, was also examined. The two genera are reciprocally monophyletic but more generic level sampling is needed to confirm an apparent sister relationship between the two.
Research Interests: Evolutionary Biology, Genetics, Zoology, North Eastern North America Archaeology, Bayesian Inference, and 15 morePhylogeny, Mitochondrial DNA, Spiders, Haplotypes, Animals, Molecular Phylogenetics and Evolution, ribosomal RNA, North America, Genetic variation, North American, Species Specificity, Bayes Theorem, Data Partitioning, Cytochrome Oxidase I, and Phylogenetic inference
Research Interests:
Gene duplication and positive selection can be important determinants of the evolution of venom, a protein-rich secretion used in prey capture and defense. In a typical model of venom evolution, gene duplicates switch to venom gland... more
Gene duplication and positive selection can be important determinants of the evolution of venom, a protein-rich secretion used in prey capture and defense. In a typical model of venom evolution, gene duplicates switch to venom gland expression and change function under the action of positive selection, which together with further duplication produces large gene families encoding diverse toxins. Although these processes have been demonstrated for individual toxin families, high-throughput multitissue sequencing of closely related venomous species can provide insights into evolutionary dynamics at the scale of the entire venom gland transcriptome. By assembling and analyzing multitissue transcriptomes from the Western black widow spider and two closely related species with distinct venom toxicity phenotypes, we do not find that gene duplication and duplicate retention is greater in gene families with venom gland biased expression in comparison with broadly expressed families. Positive...
Research Interests:
Research Interests:
Research Interests:
The evolution of specialized tissues with novel functions, such as the silk synthesizing glands in spiders, is likely an influential driver of adaptive success. Large-scale gene duplication events and subsequent paralog divergence are... more
The evolution of specialized tissues with novel functions, such as the silk synthesizing glands in spiders, is likely an influential driver of adaptive success. Large-scale gene duplication events and subsequent paralog divergence are thought to be required for generating evolutionary novelty. Such an event has been proposed for spiders, but not tested. We de novo assembled transcriptomes from three cobweb weaving spider species. Based on phylogenetic analyses of gene families with representatives from each of the three species, we found numerous duplication events indicative of a whole genome or segmental duplication. We estimated the age of the gene duplications relative to several speciation events within spiders and arachnids and found that the duplications likely occurred after the divergence of scorpions (Order Scorpionida) and spiders (Order Araneae), but before the divergence of the spider suborders Mygalomorphae and Araneomorphae, near the evolutionary origin of spider silk...
Research Interests:
Intra- and interspecific relationships of 12 out of 13 described species as well as a potential new species in the spider genus Agelenopsis (Araneae: Agelenidae) were analyzed using sequence data from two mitochondrial genes, cytochrome... more
Intra- and interspecific relationships of 12 out of 13 described species as well as a potential new species in the spider genus Agelenopsis (Araneae: Agelenidae) were analyzed using sequence data from two mitochondrial genes, cytochrome oxidase I (COI) and 16S ribosomal RNA. Approximately half of the species examined formed well-supported monophyletic groups, whereas the rest of the species were part of well-supported monophyletic species groups. Rather than viewing cases where species were not identified as being monophyletic as poor taxonomy, these cases more likely represent recent speciation and offer insights into the process of speciation. The clade with the lowest levels of interspecific sequence divergence was found in eastern North America, whereas western species displayed much higher levels of interspecific divergence. These patterns appear to extend below the species level as well, with southwestern species exhibiting the highest levels of intraspecific sequence divergen...
Research Interests: Evolutionary Biology, Genetics, Zoology, North Eastern North America Archaeology, Bayesian Inference, and 15 morePhylogeny, Mitochondrial DNA, Spiders, Haplotypes, Animals, Molecular Phylogenetics and Evolution, ribosomal RNA, North America, Genetic variation, North American, Species Specificity, Bayes Theorem, Data Partitioning, Cytochrome Oxidase I, and Phylogenetic inference
Research Interests:
Black widow venom contains α-latrotoxin, infamous for causing intense pain. Combining 33 kb of Latrodectus hesperus genomic DNA with RNA-Seq, we characterized the α-latrotoxin gene and discovered a paralog, 4.5 kb downstream. Both... more
Black widow venom contains α-latrotoxin, infamous for causing intense pain. Combining 33 kb of Latrodectus hesperus genomic DNA with RNA-Seq, we characterized the α-latrotoxin gene and discovered a paralog, 4.5 kb downstream. Both paralogs exhibit venom gland specific transcription, and may be regulated post-transcriptionally via musashi-like proteins. A 4 kb intron interrupts the α-latrotoxin coding sequence, while a 10 kb intron in the 3' UTR of the paralog may cause non-sense-mediated decay. Phylogenetic analysis confirms these divergent latrotoxins diversified through recent tandem gene duplications. Thus, latrotoxin genes have more complex structures, regulatory controls, and sequence diversity than previously proposed.
Research Interests:
Animal venoms attract enormous interest given their potential for pharmacological discovery and understanding the evolution of natural chemistries. Next-generation transcriptomics and proteomics provide unparalleled, but underexploited,... more
Animal venoms attract enormous interest given their potential for pharmacological discovery and understanding the evolution of natural chemistries. Next-generation transcriptomics and proteomics provide unparalleled, but underexploited, capabilities for venom characterization. We combined multi-tissue RNA-Seq with mass spectrometry and bioinformatic analyses to determine venom gland specific transcripts and venom proteins from the Western black widow spider (Latrodectus hesperus) and investigated their evolution. We estimated expression of 97,217 L. hesperus transcripts in venom glands relative to silk and cephalothorax tissues. We identified 695 venom gland specific transcripts (VSTs), many of which BLAST and GO term analyses indicate may function as toxins or their delivery agents. ~38% of VSTs had BLAST hits, including latrotoxins, inhibitor cystine knot toxins, CRISPs, hyaluronidases, chitinase, and proteases, and 59% of VSTs had predicted protein domains. Latrotoxins are venom ...
Research Interests:
Research Interests: Engineering, Physics, Chemistry, Biology, Medicine, and 15 moreMultidisciplinary, Phylogeny, Silk, Animals, Mass production, PLoS one, Molecular cloning, High performance, Amino Acid Profile, Species Specificity, Amino Acid Sequence, Base Sequence, Full Length Movies, Nucleotides, and Molecular Sequence Data
Research Interests:
Spider systematics has overwhelmingly relied on morphological characters to resolve higher-level phylogenetic questions. Molecular phylogenetic studies of spiders above the genus level have been rare, partly because of a paucity of... more
Spider systematics has overwhelmingly relied on morphological characters to resolve higher-level phylogenetic questions. Molecular phylogenetic studies of spiders above the genus level have been rare, partly because of a paucity of characterized genes available for amplification and sequencing. Here we show the phylogenetic utility of a new molecular marker, elongation factor-1 gamma (EF-1gamma) for discerning family level relationships in the spider infraorder, Mygalomorphae. We included genomic sequences from 26 mygalomorph genera in 14 families as well as cDNA sequences from 10 families in the infraorder Araneomorphae. We found strong support for the traditional split of mygalomorphs into atypoids (Antrodiaetidae, Atypidae, and Mecicobothriidae) and non-atypoids (all other families). Some families with multiple generic representatives were found to be polyphyletic or paraphyletic, such as the Nemesiidae, Ctenizidae, and Hexathelidae. A small portion of genomic EF-1gamma that could be amplified from araneomorphs contained a short intron, suggesting that longer genomic sequences could not be amplified due to the presence of introns. This intron may be useful for intra-familial araneomorph relationships. A tentative timeline for spider evolution is proposed using the evolutionary rate of EF-1gamma, estimated to be approximately 0.22% pairwise divergence per million years based on a non-parametric smoothing method (NPRS) and fossil constraints.
Research Interests: Evolutionary Biology, Genetics, Zoology, Molecular Evolution, Phylogeny, and 13 moreSequence alignment, Spiders, Molecular clock, Animals, Molecular Phylogenetics and Evolution, Morphological Characters, Molecular phylogenetics, EST, Evolutionary rate, Molecular Marker, Genome sequence, Base Sequence, and Molecular Sequence Data
Research Interests:
Research Interests:
Research Interests:
Research Interests: Evolutionary Biology, Genetics, Molecular Evolution, Phylogeny, Spiders, and 14 moreSilk, Animals, Molecular biology and evolution, Functional diversity, Gene Duplication, Secondary Structure, Concerted Evolution, Amino Acid Sequence, Gene Family, Biochemistry and cell biology, Differential expression, Molecular Sequence Data, Mechanical Property, and Amino acid composition
Research Interests:
... 2010 doi: 10.1636/Sh09-20.1. Silk gene transcripts in the developing tubuliform glands of the Western black widow, Latrodectus hesperus. Merri L. Casem 1 , Matthew A. Collin, Nadia A. Ayoub, and Cheryl Y. Hayashi. ... Acta Zoologica... more
... 2010 doi: 10.1636/Sh09-20.1. Silk gene transcripts in the developing tubuliform glands of the Western black widow, Latrodectus hesperus. Merri L. Casem 1 , Matthew A. Collin, Nadia A. Ayoub, and Cheryl Y. Hayashi. ... Acta Zoologica Fennica 190:209214. Moon, MJ. 2003. ...
Research Interests: Zoology and Arachnology
Hemocyanins are multimeric copper-containing hemolymph proteins involved in oxygen binding and transport in all major arthropod lineages. Most arachnids have seven primary subunits (encoded by paralogous genes a-g), which combine to form... more
Hemocyanins are multimeric copper-containing hemolymph proteins involved in oxygen binding and transport in all major arthropod lineages. Most arachnids have seven primary subunits (encoded by paralogous genes a-g), which combine to form a 24-mer (4×6) quaternary structure. Within some spider lineages, however, hemocyanin evolution has been a dynamic process with extensive paralog duplication and loss. We have obtained hemocyanin gene sequences from numerous representatives of the spider infraorders Mygalomorphae and Araneomorphae in order to infer the evolution of the hemocyanin gene family and estimate spider relationships using these conserved loci. Our hemocyanin gene tree is largely consistent with the previous hypotheses of paralog relationships based on immunological studies, but reveals some discrepancies in which paralog types have been lost or duplicated in specific spider lineages. Analyses of concatenated hemocyanin sequences resolved deep nodes in the spider phylogeny and recovered a number of clades that are supported by other molecular studies, particularly for mygalomorph taxa. The concatenated data set is also used to estimate dates of higher-level spider divergences and suggests that the diversification of extant mygalomorphs preceded that of extant araneomorphs. Spiders are diverse in behavior and respiratory morphology, and our results are beneficial for comparative analyses of spider respiration. Lastly, the conserved hemocyanin sequences allow for the inference of spider relationships and ancient divergence dates.
Research Interests:
Research Interests:
Research Interests:
Research Interests: Evolutionary Biology, Genetics, Molecular Evolution, Phylogeny, Spiders, and 11 moreExpressed Sequence Tags, Animals, Secondary Structure, Protein Secondary Structure Prediction, Amino Acid Sequence, Bayes Theorem, Tensile Strength, Gene Family, Molecular Sequence Data, Mechanical Property, and Fibroins
The evolution of specialized tissues with novel functions, such as the silk synthesizing glands in spiders, is likely an influential driver of adaptive success. Large-scale gene duplication events and subsequent paralog divergence are... more
The evolution of specialized tissues with novel functions, such as the silk synthesizing glands in spiders, is likely an influential driver of adaptive success. Large-scale gene duplication events and subsequent paralog divergence are thought to be required for generating evolutionary novelty. Such an event has been proposed for spiders, but not tested. We de novo assembled transcriptomes from three cobweb weaving spider species. Based on phylogenetic analyses of gene families with representatives from each of the three species, we found numerous duplication events indicative of a whole genome or segmental duplication. We estimated the age of the gene duplications relative to several speciation events within spiders and arachnids and found that the duplications likely occurred after the divergence of scorpions (Order Scorpionida) and spiders (Order Araneae), but before the divergence of the spider suborders Mygalomorphae and Araneomorphae, near the evolutionary origin of spider silk...
Research Interests:
Background: Spiders (Order Araneae) are essential predators in every terrestrial ecosystem largely because they have evolved potent arsenals of silk and venom. Spider silks are high performance materials made almost entirely of proteins,... more
Background: Spiders (Order Araneae) are essential predators in every terrestrial ecosystem largely because they have evolved potent arsenals of silk and venom. Spider silks are high performance materials made almost entirely of proteins, and thus represent an ideal system for investigating genome level evolution of novel protein functions. However, genomic level resources remain limited for spiders.
Results: We de novo assembled a transcriptome for the Western black widow (Latrodectus hesperus) from deeply sequenced cDNAs of three tissue types. Our multi-tissue assembly contained ~100,000 unique transcripts, of which > 27,000 were annotated by homology. Comparing transcript abundance among the different tissues, we identified 647 silk gland-specific transcripts, including the few known silk fiber components (e.g. six spider fibroins, spidroins). Silk gland specific transcripts are enriched compared to the entire transcriptome in several functions, including protein degradation, inhibition of protein degradation, and oxidation-reduction. Phylogenetic analyses of 37 gene families containing silk gland specific transcripts demonstrated novel gene expansions within silk glands, and multiple co-options of silk specific expression from paralogs expressed in other tissues.
Conclusions: We propose a transcriptional program for the silk glands that involves regulating gland specific synthesis of silk fiber and glue components followed by protecting and processing these components into functional fibers and glues. Our black widow silk gland gene repertoire provides extensive expansion of resources for biomimetic applications of silk in industry and medicine. Furthermore, our multi-tissue transcriptome facilitates evolutionary analysis of arachnid genomes and adaptive protein systems.
Results: We de novo assembled a transcriptome for the Western black widow (Latrodectus hesperus) from deeply sequenced cDNAs of three tissue types. Our multi-tissue assembly contained ~100,000 unique transcripts, of which > 27,000 were annotated by homology. Comparing transcript abundance among the different tissues, we identified 647 silk gland-specific transcripts, including the few known silk fiber components (e.g. six spider fibroins, spidroins). Silk gland specific transcripts are enriched compared to the entire transcriptome in several functions, including protein degradation, inhibition of protein degradation, and oxidation-reduction. Phylogenetic analyses of 37 gene families containing silk gland specific transcripts demonstrated novel gene expansions within silk glands, and multiple co-options of silk specific expression from paralogs expressed in other tissues.
Conclusions: We propose a transcriptional program for the silk glands that involves regulating gland specific synthesis of silk fiber and glue components followed by protecting and processing these components into functional fibers and glues. Our black widow silk gland gene repertoire provides extensive expansion of resources for biomimetic applications of silk in industry and medicine. Furthermore, our multi-tissue transcriptome facilitates evolutionary analysis of arachnid genomes and adaptive protein systems.