Identification of the ancestral killer immunoglobulin-like receptor gene in primates

BACKGROUND: Killer Immunoglobulin-like Receptors (KIR) are essential immuno-surveillance molecules. They are expressed on natural killer and T cells, and interact with human leukocyte antigens. KIR genes are highly polymorphic and contribute vital variability to our immune system. Numerous KIR genes, belonging to five distinct lineages, have been identified in all primates examined thus far and shown to be rapidly evolving. Since few KIR remain orthologous between species, with only one of them, KIR2DL4, shown to be common to human, apes and monkeys, the evolution of the KIR gene family in primates remains unclear. RESULTS: Using comparative analyses, we have identified the ancestral KIR lineage (provisionally named KIR3DL0) in primates. We show KIR3DL0 to be highly conserved with the identification of orthologues in human (Homo sapiens), common chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla), rhesus monkey (Macaca mulatta) and common marmoset (Callithrix jacchus). We predict KIR3DL0 to encode a functional molecule in all primates by demonstrating expression in human, chimpanzee and rhesus monkey. Using the rhesus monkey as a model, we further show the expression profile to be typical of KIR by quantitative measurement of KIR3DL0 from an enriched population of natural killer cells. CONCLUSION: One reason why KIR3DL0 may have escaped discovery for so long is that, in human, it maps in between two related leukocyte immunoglobulin-like receptor clusters outside the known KIR gene cluster on Chromosome 19. Based on genomic, cDNA, expression and phylogenetic data, we report a novel lineage of immunoglobulin receptors belonging to the KIR family, which is highly conserved throughout 50 million years of primate evolution

Rearrangements between the Meningococcal Genomes

<p>The dotplots were generated using MUMmer version 3.15 (<a href="http://mummer.sourceforge.net" target="_blank">http://mummer.sourceforge.net</a>) and indicate matching sequences with codirectional and reversed regions of synteny shown in red and green, respectively. Genome sequences are aligned to start/finish at the origin of replication with the approximate position of the terminus of replication indicated (Ter) (note this required rotation of the publicly available sequences for Z2491 and MC58, see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0030023#s3" target="_blank">Materials and Methods</a>). Also shown are the positions of the foci of the three major inversion events (IE1, IE2, and IE3, see text for detail).</p

NIME Array Percentage G + C Content Profile for an Array Located at 1283600–1284640 bp in the FAM18 Genome

<p>The % G + C window size is 24 bases. Maximum, minimum, and median are also shown. Red blocks represent dRS3 with inverted repeats indicated by grey triangles. Blue blocks represent RS elements.</p

Pie Charts Showing Association between Repeat Arrays and Surface Proteins in FAM18

<p>Chart sectors are coloured according to gene function (see colour key).</p

Sequence Divergence in Orthologues Flanking Repeat Arrays<b> </b>

<div><p>(A) Plot of repeat array length against flanking orthologue sequence identity for FAM18 versus Z2491 (blue diamond), Z2491 versus MC58 (red square), and FAM18 versus MC58 (green triangle).</p><p>(B) Plot of distance from array versus orthologue identity for FAM18 versus Z2491, Z2491 versus MC58, and FAM18 versus MC58.</p><p>(C) The same as (B), ignoring the first CDS.</p></div