The phylogenetic Order Diptera comprises the "true" flies (defined as having a single pair of wings arising from the thorax) and is first found in the fossil record in the Middle Triassic (~245 million years ago).  It is one of the most evolutionarily successful, comprising 120,000 known species and thought to encompass almost twice that number.  The group comprises a number of species associated with humans and with human diseases, including a number of mosquito species (Culex, Aedes, Anopheles), the tsetse fly (Glossina morsitans) and the common house fly, Musca domestica.  While some mosquito species and the tsetse fly genome have been determined previously, last October an international and interdisciplinary group* disclosed the house fly genome.  The house fly is particularly important for human health, being capable of transmitting  more than 100 human diseases.  These include:  salmonellosis, anthrax, ophthalmia, shigellosis, typhoid fever, tuberculosis, cholera and infantile diarrhea; protozoan infections including amebic dysentery; helminthic infections including pinworms, roundworms, hookworms and tapeworms; and viral and rickettsial infections.

The house fly genetic complement was known to be contained in five autosomes and an X/Y pair of sex chromosomes.  The Y chromosome contains the male dominant factor, M, but there are house fly strains known to have translocated the M factor onto any one of the 5 autosomes; these "autosomal M" males are usually XX, but M-factor mutants exist that can be female determinants.

The report, published in Genome Biology ("Genome of the house fly, Musca domestica L., a global vector of diseases with adaptations to a septic environment," 15: 466) sequenced six adult females of aabys strain; the sequenced genome size is 691 Mb and was found to contain 15,345 genes, of which 14,180 genes were predicted from open reading frames and 1,165 comprised "non-coding" genes; overall the  genes from the house fly shared ~64% identity with genes from the fruit fly Drosophila melanogaster, one of the most well-studied animal species and the best-characterized member of the Diptera.

Compared with Drosophila, the group reported detection of 49% of the predicted housefly genes to be single copy orthologs, and another 37% to comprise conserved paralogous groups, with the remaining 1,934 genes (14%) having no homologs in the Drosophila genome.  Fifty-two percent of house fly genomic DNA was found to be made up of interspersed repeats, one genomic feature that distinguishes this species from Drosophila melanogaster.  Also, about one-half of the house fly interspersed repeats are class II transposons (capable of excision and reintegration into the fly chromosome).  Gene ontology analysis found that 12.1% of the genes were involved in single-organism process and another 12% in cellular processes; 11.4% were metabolic genes and 10.8% were involved in biological regulation.  The most abundant cellular components were cell (32.6%) and organelle (29.2%).  The most abundant molecular processes were binding (48.1%) and catalytic activity (28.9%).  Overall, these breakdowns in gene ontology showed a very similar distribution to genes in Drosophila.

The significant differences involved "immune-relates" genes, genes for olefaction and genes for detoxification.  Regarding the immune-related genes, the house fly has 771 such genes, compared with 416 in Drosophila.  The putative function of these genes involved "recognition proteins that identify pathogen-associated molecular patterns, proteins that belong to signaling pathways that activate the transcriptional response to infection, and effector molecules that kill pathogens," all of which relate to similar genes in other insect species.  While immune signaling genes and their pathways are conserved compared with Drosophila, there have been "substantial increases" in both gene copy number and genic diversity for genes involved in recognition and effector components (including in particular genes, such as Nimrod and thioester-containing proteins, Teps, involved in phagocytosis, wherein there has been a large expansion of such genes in houseflies compared with Drosophila).  Of the effector protein genes, four classes of antimicrobial genes (attacins, diptericins, cecropins, and defensins) are shared with Drosophila; these have expanded in housefly (29 genes vs. 19 in Drosophila).

Another gene type having expanded in houseflies compared with Drosophila are metabolism/detoxification genes, comprising the three groups of cytochrome P450s, esterase/hydroxylases, and conjugation enzymes.

cytochrome P450s  -  146 genes (84 in Drosophila), 11 pseudogenes, largest expansion in the CYP4 (43%) and CYP6 (46%) families

esterase/hydroxylases  -  92 genes (phosphodiesterase, acetylcholinesterase, thioesterase, carboxylesterase, metallophosphoesterase, neuropathy target esterase and palmitoyl-protein thioesterase) distributed as 39 carboxylic-ester hydrolases (EC 3.1.1), 10 thioester hydrolases (EC 3.1.2), three phosphoric-monoester hydrolases (EC 3.1.3) and 40 phosphoric-diester hydrolases (EC 3.1.4)

conjugation enzymes  -  33 GST genes/3 spice variants (33/11 in Drosophila)

The Report also contains the sequences for genes involved in fast synaptic transmission, members of the cys-loop ligand-gated ion channel (cysLGIC) superfamily, with 23 subunit-encoding genes (the same as Drosophila).  These genes are important, according to the Report, as being targets for insecticides and may provide a rational basis for designing new and more effective and/or specific insecticides against the house fly.

Also reported were chemoreceptor genes in the genome, which include odorant binding proteins (OBP, 87 genes in house fly/52 genes in Drosophila), odorant receptors (OR, 85 genes (86 transcripts) in house fly/60 genes (62 transcripts) in Drosophila), gustatory receptors (GR, 79(103)/60(68)), and ionotropic receptors (IR, 110/65), with the species sharing evolutionary-conserved genes in this category but also showing rapid evolution of genes and pseudogenes; "while there are roughly equal numbers of gene losses and pseudogenes in each species, M. domestica has duplicated and retained more genes in each family.  These gene subfamily expansions are particularly prominent in the candidate gustatory receptors, especially those implicated in perception of bitter tasting compounds."  Also, "M. domestica also has large expansions of ORs related to [] receptors involved in repulsion from aversive chemicals in larvae and in perception of a male-produced pheromone."  From this data the report concludes that "M. domestica has evolved an expanded repertoire of chemoreceptors and associated proteins compared with D. melanogaster.  This expansion is mostly associated with gustation, specifically perception of bitter tasting compounds" and that "[i]t may be that the more diverse and potentially toxic food sources and larval habitats of M. domestica have led to retention and specialization of gene duplicates in these receptor gene subfamilies."

Another interesting aspect of house fly biology is sex determination and sex-biased gene expression and evolution.  The group reports sequencing of "Md-tra^D alleles of 22 to 24 individuals from 7 populations sampled across Europe, North America, Asia, Africa and Australia," finding Md-tra^D alleles on all continents; "[s]urprisingly," according to the report, the same molecular signatures in Md-tra^D alleles were found in all populations tested, "but different alleles for the non-dominant form, containing insertions or deletions in exon 3."

With there being premature translation termination in exon 2b and exon 3 mutants in males, while these lesions are "skipped" in mutant females.  With regard to sex-based expression, the report testes 10,096 genes with expression levels high enough to compare sex-related expression patterns, and found 113 having male-biased expression and 81 have female-biased expression, with no significant differencs found in the various gene ontology categories noted above.  This is a substantial difference from Drosophila, which show a ten-fold higher level of sex-based expression.

The report also notes that the house fly has five actin genes (to four in Drosophila) that have high sequence homology with Drosophila genes, and miRNA loci, showing conserved transporting/processing/function genes.

The report ends with a statement that might be applied to every advance in the genomics field with regard to the hoped-for consequences of this work:

The availability of the house fly genome should accelerate the pace of research on this important vector of human and animal diseases.  The house fly genome provides a rich resource for enabling work on innovative methods of insect control, for understanding the mechanisms of insecticide resistance, genetic adaptation to high pathogen loads, host parasitoid interactions, and for exploring the basic biology of this important pest.

* The interdisciplinary group included scientists from Cornell University, Washington University School of Medicine, the University of Groningen, the University of Zurich, the University of Illinois/Champagne-Urbana, Auburn University, the University of Houston, the National Institutes of Health, the University of Tennessee, Harvard University, and University College, London