Parasitic Wasps' Newly Sequenced Genomes Reveal New Avenues for Pest Control, Provides Insights into Evolution, Genetics
Parasitic wasps kill pest insects, but their existence is largely unknown to the public. The January 15th issue of Science features the remarkable findings from a large study to analyse the genomes of three parasitoid wasp species, revealing many features that could be useful to pest control and medicine, and to enhance our understanding of genetics and evolution: Functional and Evolutionary Insights from the Genomes of Three Parasitoid Nasonia Species. The Computational Evolutionary Genomics Group performed comparative evolutionary genomics studies as part of the international project led by John H. Werren at the University of Rochester and Stephen Richards at the Genome Sequencing Centre at the Baylor College of Medicine.
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Comparative Genomics Data
Gene Repertoire Comparisons
The predicted Nasonia gene set was compared to those of A. mellifera, Tribolium castaneum, Drosophila melanogaster, Pediculus humanus, Daphnia pulex, and Homo sapiens.
Nasonia encodes a typical insect gene repertoire, of which 60% of genes have orthologues in Human, 18% appear as arthropod-specific genes, and a small fraction of 2.4% appear to be hymenoptera-specific. An further 12% are either Nasonia-specific or without clear orthologues in the compared species.
Orthologous Groups: raw data
Group Distributions: raw data
Missing and/or Fused Genes
Potentially missed or fused genes (not in the NCBI XP_ or ab_initio gene set) were identified from orthologous groups which showed an orthologue present in most other species (P. humanus, A. mellifera, T. castaneum, D. melanogaster) except N. vitripennis, and where the A. mellifera/T. castaneum orthologue gave a significant TBLASTN hit to the N. vitripennis genome (missed) or predicted proteome (fused).
We used Genewise/Fgenesh+ predictors followed by manual refinement to suggest the best possible gene model for 68 of such Nasonia genomic regions. Notably, for six cases it proved impossible to build a respectable gene model due to gaps, stop codons, or other problems; for ten cases the predictions are likely truncated or interrupted because of the gene start/end or an internal exon is in the gap of the current genome assembly; twelve predictions overlap exons of other gene models that probably need to be corrected; and 19 predictions are in introns of other genes. Furthermore, we used the orthology evidence to refine 95 gene models that were initially fused by the automated prediction pipeline. These updates will be incorporated into future versions of the OGS.
Missing/Fused: Excel File
Gene (re-)predictions: Zipped DNA PEP and GFF files
Immune-Related Genes and Gene Families
A global scan to identify putative immune-related genes in Nasonia was based on a library of Hidden Markov Model (HMM) profiles built using carefully selected groups of immune-related proteins. The first set was built from groups of manually curated protein sequences of immune-related genes from three Dipteran species – Drosophila melanogaster, Anopheles gambiae, and Aedes aegypti - based on the Waterhouse et al. 2007 immunity analysis with all data accessible from ImmunoDB. The second set of HMMs was built from automatically defined orthologous groups across five vertebrate and five insect species, using Aedes gene identifiers as seeds to identify groups belonging to the immune repertoire. The HMM library therefore includes manually and automatically defined immune-related genes and gene (sub)families of anti-microbial peptides,gram-negative binding proteins, caspases, catalases, clip-domain serine proteases, c-type lectins, fibrinogen-related proteins, galactoside-binding lectins, inhibitors of apoptosis, IMD pathway members, JAKSTAT pathway members, lysozymes, MD2-like receptors, peptidoglycan recognition proteins, peroxidases, prophenoloxidases, scavenger receptors, superoxide dismutases, spaetzle-like proteins, serpins, thio-ester containing proteins, toll-like receptors, and TOLL pathway members. These HMMs were then run against the five different available Nasonia gene prediction sets: GLEAN, RefSeq, Augustus, Gnomon, and Fgenesh to scan for immune-related genes. They were also run against Anopheles (AgamP3.4), Aedes (AaegL1.1), and Apis (preRelease2OGS+Abinitios): cross-referencing with the ‘known’ immune repertoires defined in mosquitoes and honeybee thereby provided a cross-check on the HMM performances in terms of false positives (non immune-related genes falsely identified as such by the HMM scan) and false negatives (true immune-related genes missed by the HMM scan).
Immunity Scan Results: Excel File
We used a comparative approach on the basis of a Support Vector Machine (SVM) model of hairpin-like structures followed by an orthology assignment step. This method allows prediction of novel miRNAs that do not show sequence homology to known miRNAs. First, an ab initio SVM model was created to score stem-loop like sequences extracted from the genomic sequence with RNAfold. Second, an orthology assignment pipeline grouped putative precursors from over 40 animal species, then precursors within groups were aligned. In a third step the orthologous groups were again subjected to an SVM model designed to distinguish alignments of orthologous miRNA sequences from other ncRNA alignments or false positive predictions, taking into account typical conservation patterns in pre-miRNA sequence alignments.
miRNA Predictions: Excel File
Additional data files are attached below
“Parasitic wasps attack and kill pest insects, but many of them are smaller than the head of a pin, so people don't even notice them or know of their important role in keeping pest numbers down”, says Werren. Parasitoid wasps are like ‘smart bombs’ that seek out and kill only specific kinds of insects. Harnessing their full potential would be vastly preferable to chemical pesticides, which broadly kill or poison many organisms in the environment, including humans.
“Our contributions to the project”, says Zdobnov, “included comprehensive protein-coding and microRNA gene annotation, the identification of wasp immunity genes, and extensive comparative and phylogenomic analyses”. Overall, the wasp genome encodes a typical insect gene repertoire; 11,579 genes have recognizable relatives (orthologues) in representative species from fruit flies to humans, of which almost 7,000 genes have a human orthologue. Wasp proteins exhibit 65% median amino acid identity with orthologues of its closest sequenced relative, the honeybee, indicating a higher level of protein sequence divergence than between chicken and human (73%). “This trend”, says Zdobnov, “is also observed when examining the conservation gene order; 63% of wasp-honeybee orthologues are found in conserved genomic blocks versus 85% for chicken and human”.
The three sequenced genomes are in the wasp genus Nasonia, which is considered the "lab rat" of parasitoid insects. Among the future applications of the Nasonia genomes that could be of use in pest control are identification of genes that determine which insects a parasitoid will attack, identification of dietary needs of parasitoids to assist in their economical, large-scale rearing, and identification of parasitoid venoms that could be used in pest control. According to Zdobnov, “genes identified exclusively in wasp and honeybee compared to other sequenced genomes are likely underpin specific traits such as the stinger and venom glands”. Because parasitoid venoms manipulate cell physiology in diverse ways, they may also provide an unexpected source for new drug development.
In addition to being useful for controlling pests and offering promising venoms, the wasps could act as a new genetic system with a number of unique advantages. Fruit flies have been the standard model for genetic studies for decades, largely because they are small, can be grown easily in a laboratory, and reproduce quickly. Nasonia share these traits, but male Nasonia have only one set of chromosomes, instead of two sets like fruit flies and people. "A single set of chromosomes, which is more commonly found in lower single-celled organisms such as yeast, is a handy genetic tool, particularly for studying how genes interact with each other," says Werren. Unlike fruit flies, these wasps also modify their DNA in ways similar to humans and other vertebrates, a process called "methylation" which plays an important role in regulating how genes are turned on and off during development. “Importantly”, says Zdobnov, “our comparative analyses discovered many Nasonia genes that are shared with humans but absent from fruit flies, opening new avenues for their functional investigation in this genetically tractable parasitoid wasp”.
The wasps have an additional advantage in that closely related species of Nasonia can be cross-bred, facilitating the identification of genes involved in species' differences. "Because we have sequenced the genomes of three closely related species, we are able to study what changes have occurred during the divergence of these species from one another," says Werren. "One of the interesting findings is that DNA of mitochondria, a small organelle that "powers" the cell in organisms as diverse as yeast and people, evolves very fast in Nasonia. Because of this, the genes of the cell's nucleus that encode proteins for the mitochondria must also evolve quickly to 'keep up'." It is these co-adapting gene sets that appear to cause problems in hybrids when the species mate with each other. Research groups are now busy trying to figure out what specific kinds of interactions go wrong in the hybrid offspring. Since mitochondria are involved in a number of human diseases, as well as fertility and aging, the rapidly evolving mitochondria of Nasonia and coadapting nuclear genes could be useful research tools to investigate these processes.
"Emerging from these genome studies are a lot of opportunities for exploiting Nasonia in topics ranging from pest control to medicine, genetics, and evolution," says Werren. “However, the community of scientists working on Nasonia is still relatively small. That is why we are hoping that more scientists will see the utility of these insects, and join in efforts to exploit their potential.” “Insects are the most diverse group of terrestrial animals”, says Zdobnov, “and the sequencing of the wasp genome significantly augments the opportunities for scientists to examine the genetic basis of this incredible diversity that underlies their success”.