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Conservation, Extensive Heterozygosity, and Convergence of Signaling Potential All Indicate a Critical Role for KIR3DL3 in Higher Primates.

ABSTRACT: Natural killer (NK) cell functions are modulated by polymorphic killer cell immunoglobulin-like receptors (KIR). Among 13 human KIR genes, which vary by presence and copy number, KIR3DL3 is ubiquitously present in every individual across diverse populations. No ligand or function is known for KIR3DL3, but limited knowledge of expression suggests involvement in reproduction, likely during placentation. With 157 human alleles, KIR3DL3 is also highly polymorphic and we show heterozygosity exceeds that of HLA-B in many populations. The external domains of catarrhine primate KIR3DL3 evolved as a conserved lineage distinct from other KIR. Accordingly, and in contrast to other KIR, we show the focus of natural selection does not correspond exclusively to known ligand binding sites. Instead, a strong signal for diversifying selection occurs in the D1 Ig domain at a site involved in receptor aggregation, which we show is polymorphic in humans worldwide, suggesting differential ability for receptor aggregation. Meanwhile in the cytoplasmic tail, the first of two inhibitory tyrosine motifs (ITIM) is conserved, whereas independent genomic events have mutated the second ITIM of KIR3DL3 alleles in all great apes. Together, these findings suggest that KIR3DL3 binds a conserved ligand, and a function requiring both receptor aggregation and inhibitory signal attenuation. In this model KIR3DL3 resembles other NK cell inhibitory receptors having only one ITIM, which interact with bivalent downstream signaling proteins through dimerization. Due to the extensive conservation across species, selection, and other unusual properties, we consider elucidating the ligand and function of KIR3DL3 to be a pressing question.

SUBMITTER: Leaton LA

PROVIDER: S-EPMC6360152 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Small freshwater ponds host diverse and vulnerable biotic assemblages but relatively few conspicuous, specially protected taxa. In Europe, the amphibians Triturus cristatus and Pelobates fuscus are among a few species whose populations have been successfully restored using pond restoration and management activities at the landscape scale. In this study, we explored whether the ponds constructed for those two target species have wider conservation significance, particularly for other species of conservation concern. We recorded the occurrence of amphibians and selected aquatic macro-invertebrates (dragonflies; damselflies; diving beetles; water scavenger beetles) in 66 ponds specially constructed for amphibians (up to 8 years post construction) and, for comparison, in 100 man-made ponds (created by local people for cattle or garden watering, peat excavation, etc.) and 65 natural ponds in Estonia. We analysed nestedness of the species assemblages and its dependence on the environment, and described the co-occurrence patterns between the target amphibians and other aquatic species. The assemblages in all ponds were significantly nested, but the environmental determinants of nestedness and co-occurrence of particular species differed among pond types. Constructed ponds were most species-rich irrespective of the presence of the target species; however, T. cristatus was frequent in those ponds and rare elsewhere, and it showed nested patterns in every type of pond. We thus conclude that pond construction for the protected amphibians can serve broader habitat conservation aims in the short term. However, the heterogeneity and inconsistent presence of species of conservation concern observed in other types of ponds implies that long-term perspectives on pond management require more explicit consideration of different habitat and biodiversity values. We also highlight nestedness analysis as a tool that can be used for the practical task of selecting focal species for habitat conservation.

Dataset Information

Conservation, Extensive Heterozygosity, and Convergence of Signaling Potential All Indicate a Critical Role for KIR3DL3 in Higher Primates.

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