title: Genome content analysis yields new insights into the relationship between the human malaria parasite Plasmodium falciparum and its anopheline vectors.
abstract: The persistent and growing gap between the availability of sequenced genomes and the ability to assign functions to sequenced genes led us to explore ways to maximize the information content of automated annotation for studies of anopheline mosquitos. Specifically, we use genome content analysis of a large number of previously sequenced anopheline mosquitos to follow the loss and gain of protein families over the evolutionary history of this group. The importance of this endeavor lies in the potential for comparative genomic studies between Anopheles and closely related non-vector species to reveal ancestral genome content dynamics involved in vector competence. In addition, comparisons within Anopheles could identify genome content changes responsible for variation in the vectorial capacity of this family of important parasite vectors.
  
  
  
  The competence and capacity of P. falciparum vectors do not appear to be phylogenetically constrained within the Anophelinae. Instead, using ancestral reconstruction methods, we suggest that a previously unexamined component of vector biology, anopheline nucleotide metabolism, may contribute to the unique status of anophelines as P. falciparum vectors. While the fitness effects of nucleotide co-option by P. falciparum parasites on their anopheline hosts are not yet known, our results suggest that anopheline genome content may be responding to selection pressure from P. falciparum. Whether this response is defensive, in an attempt to redress improper nucleotide balance resulting from P. falciparum infection, or perhaps symbiotic, resulting from an as-yet-unknown mutualism between anophelines and P. falciparum, is an open question that deserves further study.
  
  
  
  Clearly, there is a wealth of functional information to be gained from detailed manual genome annotation, yet the rapid increase in the number of available sequences means that most researchers will not have the time or resources to manually annotate all the sequence data they generate. We believe that efforts to maximize the amount of information obtained from automated annotation can help address the functional annotation deficit that most evolutionary biologists now face, and here demonstrate the value of such an approach.
authors.affiliation: Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, NY, 10024, USA. soppenheim@amnh.org.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Oppenheim
authors.affiliation: Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, NY, 10024, USA.|Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Rosenfeld
authors.affiliation: Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, NY, 10024, USA.
authors.forename: Rob
authors.initials: R
authors.lastname: DeSalle
mesh_terms: D000818:Animals; D000852:Anopheles / Q000145:classification / Q000235:genetics*; D002874:Chromosome Mapping; D049750:Genome, Insect; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D007303:Insect Vectors / Q000235:genetics*; D016778:Malaria, Falciparum / Q000469:parasitology* / Q000473:pathology; D009711:Nucleotides / Q000378:metabolism; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000235:genetics*
chemical_list: D019476:Insect Proteins; D009711:Nucleotides
keywords: Anopheles; Automatic annotation; Gene ontology; Genome content; Malaria; Plasmodium falciparum; Vector-parasite interactions