Loss and Gain of Natural Killer Cell Receptor Function in an African Hunter-Gatherer Population

Modulating natural killer cell functions in human immunity and reproduction are diverse interactions between the killer cell immunoglobulin-like receptors (KIR) of Natural Killer (NK) cells and HLA class I ligands on the surface of tissue cells. Dominant interactions are between KIR2DL1 and the C2 epitope of HLA-C and between KIR2DL2/3 and the C1 epitope of HLA-C. KhoeSan hunter-gatherers of Southern Africa represent the earliest population divergence known and are the most genetically diverse indigenous people, qualities reflected in their KIR and HLA genes. Of the ten KhoeSan KIR2DL1 alleles, KIR2DL1*022 and KIR2DL1*026 likely originated in the KhoeSan, and later were transmitted at low frequency to the neighboring Zulus through gene flow. These alleles arose by point mutation from other KhoeSan KIR2DL1 alleles that are more widespread globally. Mutation of KIR2DL1*001 gave rise to KIR2DL1*022, causing loss of C2 recognition and gain of C1 recognition. This makes KIR2DL1*022 a more avid and specific C1 receptor than any KIR2DL2/3 allotype. Mutation of KIR2DL1*012 gave rise to KIR2DL1*026, causing premature termination of translation at the end of the transmembrane domain. This makes KIR2DL1*026 a membrane-associated receptor that lacks both a cytoplasmic tail and signaling function. At higher frequencies than their parental allotypes, the combined effect of the KhoeSan-specific KIR2DL1*022 and KIR2DL1*026 is to reduce the frequency of strong inhibitory C2 receptors and increase the frequency of strong inhibitory C1 receptors. Because interaction of KIR2DL1 with C2 is associated with risk of pregnancy disorder, these functional changes are potentially advantageous. Whereas all other KhoeSan KIR2DL1 alleles are present on a wide diversity of centromeric KIR haplotypes, KIR2DL1*026 is present on a single KIR haplotype and KIR2DL1*022 is present on two very similar haplotypes. The high linkage disequilibrium across their haplotypes is consistent with a recent emergence for these KIR2DL1 alleles that have distinctive functions.     

Large‐Scale Zostera marina (eelgrass) Restoration in Chesapeake Bay,Maryland, USA. Part II: A Comparison of Restoration Methods in the Patuxent and Potomac Rivers

In response to systemic losses of submerged aquatic vegetation (SAV) in the Chesapeake Bay (east coast of North America), the U.S. Environmental Protection Agency's (EPA) Chesapeake Bay Program (CBP) and Maryland Department of Natural Resources (MD DNR) have considered SAV restoration a critical component in Bay restoration programs. In 2003, the CBP created the “Strategy to Accelerate the Protection and Restoration of Submerged Aquatic Vegetation in the Chesapeake Bay” in an effort to increase SAV area. As part of this strategy, large‐scale eelgrass (Zostera marina) restoration efforts were initiated in the Patuxent and Potomac Rivers in Maryland. From 2004 to 2007, nearly 4 million Z. marina seeds were dispersed over 10 ha on the Patuxent River and almost 9 million seeds over 16 ha on the Potomac River. Z. marina seedling establishment was consistent throughout the project (<4%); however, restored eelgrass survival was highly dependent on restoration site. Restoration locations on the Patuxent River experienced initial Z. marina seedling germination, but no long‐term plant survival. Restored Z. marina on the Potomac River has persisted and expanded, both vegetatively and sexually, beyond initial seeding areas. Healthy Z. marina beds now cover approximately five acres of the Potomac River bottom for the first time in decades. The differential success of Z. marina restoration efforts in the two rivers is evidence for the necessity of carefully considering site‐specific characteristics when using large‐scale seeding methods to achieve successful SAV restoration.     

Evaluating a Large‐Scale Eelgrass Restoration Project in the Chesapeake Bay

Approximately 90,000 shoots of eelgrass (Zostera marina) were planted over 3 years (2003–2005) at Piney Point (PP) in the lower Potomac River estuary in the Chesapeake Bay (mid‐Atlantic coast of North America) following 3 years of habitat evaluation using a Preliminary Transplant Suitability Index (PTSI) and test plantings. Initial survival was high for the 2003 and 2004 plantings; however, most of the eelgrass died during the summer following the fall planting. Habitat quality and restoration success were monitored for the 2005 plantings and compared to a nearby restoration site (St. George Island [SGI]). Eelgrass planted at PP in the fall of 2005 declined through the summer of 2006 with some recovery in the spring of 2007, but was gone by the end of the summer of 2007. The summer decline from late July to mid‐August of 2006 coincided with water temperatures greater than 30°C, hypoxic oxygen (0–3 mg/L) concentrations, and low percent light at leaf level (PLL < 15%). Epiphyte loads were much heavier at PP than at SGI, despite similar water quality. We suggest that this was the result of higher wave exposure at PP. All of these factors are likely to have contributed to the mortality of the 2005 plantings. Submerged aquatic vegetation habitat quality based on the PTSI, median PLL during the growing season, and test plantings did not explain the decline of the plantings. Restoration site selection criteria should be expanded to include the effects of wave exposure on self‐shading and epiphyte loads, and the potential for both short‐term exposures to stressful conditions and long‐term changes in habitat quality.     

The complete mitochondrial genome of the enigmatic bigheaded turtle (Platysternon): description of unusual genomic features and the reconciliation of phylogenetic hypotheses based on mitochondrial and nuclear DNA

Background  

The big-headed turtle (Platysternon megacephalum) from east Asia is the sole living representative of a poorly-studied turtle lineage (Platysternidae). It has no close living relatives, and its phylogenetic position within turtles is one of the outstanding controversies in turtle systematics. Platysternon was traditionally considered to be close to snapping turtles (Chelydridae) based on some studies of its morphology and mitochondrial (mt) DNA, however, other studies of morphology and nuclear (nu) DNA do not support that hypothesis.     

The phylogeny of Mediterranean tortoises and their close relatives based on complete mitochondrial genome sequences from museum specimens

As part of an ongoing project to generate a mitochondrial database for terrestrial tortoises based on museum specimens, the complete mitochondrial genome sequences of 10 species and a approximately 14kb sequence from an eleventh species are reported. The sampling of the present study emphasizes Mediterranean tortoises (genus Testudo and their close relatives). Our new sequences are aligned, along with those of two testudinoid turtles from GenBank, Chrysemys picta and Mauremys reevesii, yielding an alignment of 14,858 positions, of which 3238 are parsimony informative. We develop a phylogenetic taxonomy for Testudo and related species based on well-supported, diagnosable clades. Several well-supported nodes are recovered, including the monophyly of a restricted Testudo, T. kleinmanni+T. marginata (the Chersus clade), and the placement of the enigmatic African pancake tortoise (Malacochersus tornieri) within the predominantly Palearctic greater Testudo group (Testudona tax. nov.). Despite the large amount of sequence reported, there is low statistical support for some nodes within Testudona and so we do not propose names for those groups. A preliminary and conservative estimation of divergence times implies a late Miocene diversification for the testudonan clade (6-10 million years ago), matching their first appearance in the fossil record. The multi-continental distribution of testudonan turtles can be explained by the establishment of permanent connections between Europe, Africa, and Asia at this time. The arrival of testudonan turtles to Africa occurred after one or more initial tortoise invasions gave rise to the diverse (>25 species) 'Geochelone complex.' Two unusual genomic features are reported for the mtDNA of one tortoise, M. tornieri: (1) nad4 has a shift of reading frame that we suggest is resolved by translational frameshifting of the mRNA on the ribosome during protein synthesis and (2) there are two copies of the control region and trnF, with the latter having experienced multiple-nucleotide substitutions in a pattern suggesting that each is being maintained by selection.     

Evolutionary disruptions of human syntenic groups 3, 12, 14, and 15 in Ateles paniscus chamek (Platyrrhini, primates)

Comparative gene assignments of 18 markers, based on analyses of somatic cell hybrids and previous data in the literature, indicated that human (HSA) syntenic groups 3, 12, 14, and 15 are dissociated in the spider monkey species Ateles paniscus chamek (APC). Markers present in HSA 3p were allocated to APC 3 and APC 9. The HSA 12 cluster was split into two syntenic groups, one mainly including HSA 12p markers in APC 16 and the other, including HSA 12q markers, in APC 2p. The HSA 14q cluster split into three syntenic groups, corresponding to APC 2q, APC 6, and APC 12. Finally, the HSA 15 cluster split into two syntenic groups, APC 2q and APC 3. Comparisons with previous gene assignments and human SROs led to the tentative postulation of rearrangements having occurred during the evolutionary divergence of man and A. paniscus chamek. Chromosome painting data in the congeneric species A. geoffroyi, other New World and Old World primates, and several representative non-primate animals were compared in an attempt to delineate the ancestral and derived conditions underlying the evolutionary rearrangement of syntenic groups in mammals.     

Human KIR sequences 2003

We have compiled the nucleotide sequences and their amino acid translations from a total of 89 Killer Immunoglobulin-like Receptor (KIR) alleles, derived from 17 different KIR genes. The alignments use the KIR3DL2*001 allele as a reference sequence. Each of the KIR sequences included in these alignments has been checked and where discrepancies have arisen between reported sequences, the original authors have been contacted where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation.     

Distinctive KIR and HLA diversity in a panel of north Indian Hindus

HLA and KIR are diverse and rapidly evolving gene complexes that work together in human immunity mediated by cytolytic lymphocytes. Understanding their complex immunogenetic interaction requires study of both HLA and KIR diversity in the same human population. Here a panel of 72 unrelated north Indian Hindus was analyzed. HLA- A, B, C, DRB1, DQA1, and DQB1 alleles and their frequencies were determined by sequencing or high-resolution typing of genomic DNA; KIR genotypes were determined by gene-specific typing and by allele-level DNA typing for KIR2DL1, 2DL3, 2DL5, 3DL1, and 3DL2. From HLA analysis, the north Indian population is seen to have several characteristics shared either with Caucasian or East Asian populations, consistent with the demographic history of north India, as well as specific features, including several alleles at high frequency that are rare or absent in other populations. A majority of the north Indian KIR gene profiles have not been seen in Caucasian and Asian populations. Most striking is a higher frequency of the B group of KIR haplotypes, resulting in equal frequencies for A and B group haplotypes in north Indians. All 72 members of the north Indian panel have different HLA genotype and different KIR genotype.     

A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit,IL-23R

IL-23 is a heterodimeric cytokine composed of the IL-12p40 "soluble receptor" subunit and a novel cytokine-like subunit related to IL-12p35, termed p19. Human and mouse IL-23 exhibit some activities similar to IL-12, but differ in their capacities to stimulate particular populations of memory T cells. Like IL-12, IL-23 binds to the IL-12R subunit IL-12Rbeta1. However, it does not use IL-12Rbeta2. In this study, we identify a novel member of the hemopoietin receptor family as a subunit of the receptor for IL-23, "IL-23R." IL-23R pairs with IL-12Rbeta1 to confer IL-23 responsiveness on cells expressing both subunits. Human IL-23, but not IL-12, exhibits detectable affinity for human IL-23R. Anti-IL-12Rbeta1 and anti-IL-23R Abs block IL-23 responses of an NK cell line and Ba/F3 cells expressing the two receptor chains. IL-23 activates the same Jak-stat signaling molecules as IL-12: Jak2, Tyk2, and stat1, -3, -4, and -5, but stat4 activation is substantially weaker and different DNA-binding stat complexes form in response to IL-23 compared with IL-12. IL-23R associates constitutively with Jak2 and in a ligand-dependent manner with stat3. The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12Rbeta2, respectively. The human IL-23R gene is on human chromosome 1 within 150 kb of IL-12Rbeta2.     

Definition of gene content for nine common group B haplotypes of the Caucasoid population: KIR haplotypes contain between seven and eleven KIR genes

The segregation of killer cell immunoglobulin-like receptor ( KIR) genes was determined for a panel of 21 Caucasoid families: 23 different KIR gene patterns were found and could be assigned to combinations of 16 different haplotypes. Four loci were held in common by all haplotypes: KIR2DL4, KIR3DL2, the putative pseudogene KIR3DL3 and KIR2DL2/KIR2DL3, the latter likely being alleles of one gene. Group A haplotypes, which have a unique combination of seven KIR genes, were found at 80% frequency in the family panel, the polygenic group B haplotypes at 65% frequency. KIR gene segregation was fully determined for the nine group B haplotypes, which occurred at highest frequencies in both the family panel and a panel of unrelated individuals. The group B haplotypes carried between seven and 11 KIR genes and encoded inhibitory KIR for one, two, or all three major HLA class I epitopes. Analysis of human leucocyte antigen (HLA) class I genotypes revealed that most, but not all, individuals possess an inhibitory KIR for a self HLA class I epitope. The number of stimulatory KIR genes in group B haplotypes varied considerably between one and five. The data show that group B haplotypes possess a broad spectrum of KIR gene patterns, which is largely complementary to the KIR gene set of group A haplotypes. The results suggest that rapid diversification of group B haplotypes is the result of pathogen-mediated selection for KIR genotypes that have more than the set of KIR genes provided by the group A haplotype.