The role of genomic data in the discovery, annotation and evolutionary interpretation of the interferon-lambda family.
BACKGROUND
Type-I interferons, type-II interferons, and the IL-10 family are helical cytokines with similar three-dimensional folds. However, their homologous relationship is difficult to detect on the basis of sequence alone. We have previously described the discovery of the human type-III interferons (IFN lambda-1, -2, -3 or IL-29, IL-28A, IL-28B), which required a combination of manual and computational techniques applied to predicted protein sequences.


RESULTS
Here we describe how the use of gene structure analysis and comparative genomics enabled a more extensive understanding of these genes early in the discovery process. More recently, additional mammalian genome sequences have shown that there are between one and potentially nine copies of interferon lambda genes in each genome, and that several species have single exon versions of the interferon lambda gene.


CONCLUSIONS
The variable number of single exon type-I interferons in mammals, along with recently identified genes in zebrafish homologous to interferons allows a story of interferon evolution to be proposed. This model suggests that the gene duplications and single exon retrotransposons of mammalian type-III interferons are positively selected for within a genome. These characteristics are also shared with the fish interferons and could be responsible for the generation of the IL10 family and also the single exon type-I interferons.
Fox
Brian A
BA
Bioinformatics Department, ZymoGenetics, Inc, Seattle, Washington, United States of America. bfox@novonordisk.com
Sheppard
Paul O
PO
O'Hara
Patrick J
PJ
D000818:Animals; D001483:Base Sequence; D019143:Evolution, Molecular; D005091:Exons; D023281:Genomics; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000145:classification / Q000235:genetics*; D007438:Introns; D008969:Molecular Sequence Data; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D000095022:Interferon Lambda
D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda