The allotypic patchwork pattern of the rabbit IGKC1 allele b5wf: genic exchange or common ancestry?

 The protein sequences of different alleles of the rabbit immunoglobulin IGKC1 gene can differ at more than 40% of the amino acid positions. This exceptional degree of allelic divergence raises questions concerning the causal underlying mechanisms. We report the DNA sequence of the coding region of an allotype which is associated with the mitochondrial lineage A (Southwestern Spain). At the serological level, this b5wf allotype presents a patchwork of antigenic determinants which in domestic breeds are characteristic of the b4, b5, and b6 allotypes. The inferred protein sequence of the b5wf allotype was found to differ from that of the b4, b5, and b6 allotypes at 25, 10, and 15% of the amino acid positions, respectively. Sequence comparisons show that the b4-specific epitopes of the b5wf allotype are probably due to a shared ThrThrGlnThr motif at Kabat positions 153–156. Similarly, the shared b5-specific determinants should relate to the motifs 161ThrSerLys163 and/or 182LysSerAspGlu185. A monoclonal antibody binding epitope shared among the b5wf, b5, and b6 sequences appeared to be correlated with the presence of Asp190. Although there is evidence of interallelic genic exchange, sequence comparisons suggest that the apparent mosaic structure of the b5wf allotype is better explained by common ancestry and point mutation. Received: 22 June 1998 / Revised: 18 August 1998     

Virus-immune dynamics determined by prey-predator interaction network and epistasis in viral fitness landscape

The emergence and persistence of polymorphism within populations generally requires specific regimes of natural or sexual selection. Here, we develop a unified theoretical framework to explore how polymorphism at targeted loci can be generated and maintained by either disassortative mating choice or balancing selection due to, for example, heterozygote advantage. To this aim, we model the dynamics of alleles at a single locus A in a population of haploid individuals, where reproductive success depends on the combination of alleles carried by the parents at locus A. Our theoretical study of the model confirms that the conditions for the persistence of a given level of allelic polymorphism depend on the relative reproductive advantages among pairs of individuals. Interestingly, equilibria with unbalanced allelic frequencies were shown to emerge from successive introduction of mutants. We then investigate the role of the function linking allelic divergence to reproductive advantage on the evolutionary fate of alleles within the population. Our results highlight the significance of the shape of this function for both the number of alleles maintained and their level of genetic divergence. Large number of alleles are maintained with substantial replacement of alleles, when disassortative advantage slowly increases with allelic differentiation . In contrast, few highly differentiated alleles are predicted to be maintained when genetic differentiation has a strong effect on disassortative advantage. These opposite effects predicted by our model explain how disassortative mate choice may lead to various levels of allelic differentiation and polymorphism, and shed light on the effect of mate preferences on the persistence of balanced and unbalanced polymorphism in natural population.

     

Mhc class II B gene evolution in East African cichlid fishes

 A distinctive feature of essential major histocompatibility complex (Mhc) loci is their polymorphism characterized by large genetic distances between alleles and long persistence times of allelic lineages. Since the lineages often span several successive speciations, we investigated the behavior of the Mhc alleles during or close to the speciation phase. We sequenced exon 2 of the class II B locus 4 from 232 East African cichlid fishes representing 32 related species. The divergence times of the (sub)species ranged from 6000 to 8.4 million years. Two types of evolutionary analysis were used to elucidate the pattern of exon 2 sequence divergence. First, phylogenetic methods were applied to reconstruct the most likely evolutionary pathways leading from the last common ancestor of the set to the extant sequences, and to assess the probable mechanisms involved in allelic diversification. Second, pairwise comparisons of sequences were carried out to detect differences seemingly incompatible with origin by nonparallel point mutations. The analysis revealed point mutations to be the most important mechanism behind allelic divergences, with recombination playing only an auxiliary part. Comparison of sequences from related species revealed evidence of random allelic (lineage) losses apparently associated with speciation. Sharing of identical alleles could be demonstrated between species that diverged 2 million years ago. The phylogeny of the exon was incongruent with that of the flanking introns, indicating either a high degree of convergent evolution at the peptide-binding region-encoding sites, or intron homogenization. Received: 6 December 1999 / Revised: 15 February 2000     

Isolation and introgression in the Intermountain West: contrasting gene genealogies reveal the complex biogeographic history of the American pika (Ochotona princeps)

Aim We studied the history of colonization, diversification and introgression among major phylogroups in the American pika, Ochotona princeps (Lagomorpha), using comparative and statistical phylogeographic methods. Our goal was to understand how Pleistocene climatic fluctuations have shaped the distribution of diversity at mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) loci in this alpine specialist. Location North America’s Intermountain West. Methods We accumulated mtDNA sequence data (c. 560–1700 bp) from 232 pikas representing 64 localities, and sequenced two nuclear introns (mast cell growth factor, c. 550 bp, n = 148; protein kinase C iota, c. 660 bp, n = 139) from a subset of individuals. To determine the distribution of major mtDNA lineages, we conducted a phylogenetic analysis on the mtDNA sequence data, and we calculated divergence times among the lineages using a Bayesian Markov chain Monte Carlo approach. Relationships among nuclear alleles were explored with minimum spanning networks. Finally, we conducted coalescent simulations of alternative models of population history to test for congruence between nDNA and mtDNA responses to Pleistocene glacial cycles. Results We found that: (1) all individuals could be assigned to one of five allopatric mtDNA lineages; (2) lineages are associated with separate mountain provinces; (3) lineages originated from at least two rounds of differentiation; (4) nDNA and mtDNA markers exhibited overall phylogeographic congruence; and (5) introgression among phylogroups has occurred at nuclear loci since their initial isolation. Main conclusions Pika populations associated with different mountain systems have followed separate but not completely independent evolutionary trajectories through multiple glacial cycles. Range expansion associated with climate cooling (i.e. glaciations) promoted genetic admixture among populations within mountain ranges. It also permitted periodic contact and introgression between phylogroups associated with different mountain systems, the record of which is retained at nDNA but not mtDNA loci. Evidence for different histories at nuclear and mtDNA loci (i.e. periodic introgression versus deep isolation, respectively) emphasizes the importance of multilocus perspectives for reconstructing complete population histories.     

Characterization of Mhc-DRB allelic diversity in white-tailed deer (Odocoileus virginianus) provides insight into Mhc-DRB allelic evolution within Cervidae

 Although white-tailed deer (Odocoileus virginianus) are one of North America's best studied mammals, no information is available concerning allelic diversity at any locus of the major histocompatibility complex in this taxon. Using the polymerase chain reaction, single-stranded conformation polymorphism analysis, and DNA sequencing techniques, 15 DRB exon 2 alleles were identified among 150 white-tailed deer from a single population in southeastern Oklahoma. These alleles represent a single locus and exhibit a high degree of nucleotide and amino acid polymorphism, with most amino acid variation occurring at positions forming the peptide binding sites. Furthermore, twenty-seven amino acid residues unique to white-tailed deer DRB alleles were detected, with 19 of these occurring at residues forming contact points of the peptide binding region. Significantly higher rates of nonsynonymous than synonymous substitutions were detected among these DRB alleles. In contrast to other studies of Artiodactyla DRB sequences, interallelic recombination does not appear to be playing a significant role in the generation of allelic diversity at this locus in white-tailed deer. To examine evolution of white-tailed deer (Odvi-DRB) alleles within Cervidae, we performed a phylogenetic analysis of all published red deer (Ceel-DRB), roe deer (Caca-DRB), and moose (Alal-DRB) DRB alleles. The phylogenetic tree clearly shows a trans-species persistence of DRB lineages among these taxa. Moreover, this phylogenetic tree provides insight into evolution of DRB allelic lineages within Cervidae and may aid in assignment of red deer DRB alleles to specific loci. Received: 25 June 1998 / Revised: 2 September 1998     

Trans-species polymorphism of class IIMhc loci in danio fishes

 A characteristic feature of the major histocompatibility complex (Mhc) polymorphism in mammals is the existence of allelic lineages shared by related species. This trans-species polymorphism has thus far been documented only in primates, rodents, and artiodactyls. In this communication we provide evidence that it also exists in cyprinid (bony) fishes at the class II A and B loci coding for the α and β polypeptide chains of the class II α : β heterodimers. The study has focused on three species of the family Cyprinidae, subfamily Rasborinae: the zebrafish (Danio rerio), the giant danio (D. malabaricus), and the pearl danio (D. albolineatus). The polymerase chain reaction was used to amplify and then sequence intron 1 and exon 2 of the class II B loci and exon 2 of the class II A loci in these species. Phylogenetic analysis of the sequences revealed the existence of allelic lineages whose divergence predates the divergence of the three species at both the A and B loci. The lineages at the B locus in particular are separated by large genetic distances. The polymorphism is concentrated in the peptide-binding region sites and is apparently maintained by balancing selection. Sharing of this unique Mhc feature by both bony fishes and mammals suggests that the main function of the Mhc (presentation of peptides to T lymphocytes) has not changed during the last 400 million years of its evolution. Received: 6 December 1995 / Revised: 6 February 1996     

Mito‐nuclear discord in six congeneric lineages of Holarctic ducks (genus Anas)

Many species have Holarctic distributions that extend across Europe, Asia and North America. Most genetics research on these species has examined only mitochondrial (mt) DNA, which has revealed wide variance in divergence between Old World (OW) and New World (NW) populations, ranging from shallow, unstructured genealogies to deeply divergent lineages. In this study, we sequenced 20 nuclear introns to test for concordant patterns of OW–NW differentiation between mtDNA and nuclear (nu) DNA for six lineages of Holarctic ducks (genus Anas). Genetic differentiation for both marker types varied widely among these lineages (idiosyncratic population histories), but mtDNA and nuDNA divergence within lineages was not significantly correlated. Moreover, compared with the association between mtDNA and nuDNA divergence observed among different species, OW–NW nuDNA differentiation was generally lower than mtDNA divergence, at least for lineages with deeply divergent mtDNA. Furthermore, coalescent estimates indicated significantly higher rates of gene flow for nuDNA than mtDNA for four of the six lineages. Thus, Holarctic ducks show prominent mito‐nuclear discord between OW and NW populations, and we reject differences in sorting rates as the sole cause of the within‐species discord. Male‐mediated intercontinental gene flow is likely a leading contributor to this discord, although selection could also cause increased mtDNA divergence relative to weak nuDNA differentiation. The population genetics of these ducks contribute to growing evidence that mtDNA can be an unreliable indicator of stage of speciation and that more holistic approaches are needed for species delimitation.     

Polymorphism, natural selection, and structural modeling of class Ia MHC in the African clawed frog (Xenopus laevis)

In the African clawed frog (Xenopus laevis), two deeply divergent allelic lineages of multiple genes of the class I MHC region have been discovered. For the MHC class I UAA locus, functional differences and the molecular basis for lineages maintenance are unknown. Alleles of linked class I region genes also exhibit strong disequilibrium with specific MHC alleles, but the underlying cause is not clear. We use MHC class Ia sequence data to estimate substitution rates and investigate structural differences between allelic lineages from protein models. Results indicate the operation of natural selection, and differences in the steric properties in the F pocket of the peptide-binding region among lineages. Variability in this pocket likely enables allelic lineages to bind very different sets of peptides and to interact differently with MHC chaperones in the endoplasmic reticulum. These results constitute evidence of the molecular evolutionary basis for 1) the maintenance of allelic lineages, 2) functional differences among lineages, and 3) strong linkage disequilibrium of allelic variants of class I region genes in X. laevis.Electronic Supplementary Material Supplementary material is available for this article at     

Mitochondrial DNA variability in viviparous and ovoviviparous populations of the urodele Salamandra salamandra

Mitochondrial DNA analysis of 13 populations of S. salamandra along a transect across the North of the Iberian Peninsula showed values of divergence between haplotypes ranging from d = 0.41% to 5.91%. Phenetic and cladistic analysis grouped the isofemale lineages into two main clusters with contrasting phylogeographic patterns. The first group encompasses populations located at each extreme of the Iberian Peninsula. Despite the large geographic distance separating these populations, they exhibit only a minor degree of divergence among haplotypes. In contrast, much higher diversification, in both number of distinct haplotypes, and overall genetic divergence, was observed in the second group of phylogenetically related populations. Surprisingly, this process of radiation and divergence in mtDNA haplotypes occurred in populations in close geographic proximity. All populations sampled in this group are located within a 300 km range, in the central part of our transect across the Northern edge of the Peninsula. Most populations in the central range of our transect exhibit viviparous reproduction — which is derived and highly unusual among urodeles. The genetic distances measured among Asturian (central portion of our transect), viviparous populations are higher than the distances measured between the two main taxonomic clusters. A viviparous population showing an unusual level of mtDNA heterogenetiy is reported and the potential implications of this focus of localized variability are discussed. The dynamics of isofemale lineages among the two reproductive modes was further explored in combination with the previous allozyme data. Several nuclear markers suggest that major mtDNA divergences could be explained by long-term extrinsic barriers to gene flow. Isofemale lineages indicate a narrow secondary contact zone among populations with different reproductive patterns. The existence of viviparous and ovovivparous populations sharing a common haplotype suggests that reproductive transition in S. salamandra could have arisen in absence of genetic mtDNA differentiation. We finally outline a genetic model system where the acquisition of water independence from a primitively aquatic dependent amphibian life cycle can be analyzed from a microevolutionary perspective.     

Transfer of mitochondrial DNA from the northern red-backed vole (Clethrionomys rutilus) to the bank vole (C. glareolus)

Summary Using a silver staining method to detect DNA fragments produced by restriction enzymes, it was possible to compare mitochondrial DNAs (mtDNAs) from 85 individuals of the bank vole (Clethrionomys glareolus) trapped at 25 localities in Fennoscandia. There are two distinctly different mtDNA lineages, one occurring in southern and central Fennoscandia and the other in the northern parts. A fragment comparison method shows about 12.7% nucleotide sequence divergence between these two lineages. This major difference between animals of the same species could theoretically be explained by intraspecific lineage survivorship independent of species hybridization, or by introduction of an atypical mtDNA via hybridization with a closely related species. Analysis of mtDNAs from the two otherClethrionomys species present in Fennoscandia (C. rutilus andC. rufocanus) shows that the mtDNA of northernC. glareolus is very similar to that ofC. rutilus and that the mtDNA lineages of these two species cluster together in a phenogram, with small genetic distances among them. By contrast, electrophoresis of proteins encoded by 17 nuclear loci reveals fixed allelic differences between these two species at 8 loci. Hence the presence of two distinctly different mtDNA lineages withinC. glareolus may be a consequence of a limited episode of hybridization betweenC. glareolus andC. rutilus, probably during the postglacial recolonization of Fennoscandia 8000–13,000 years ago.     

Relic of ancient recombinations in gibbon ABO blood group genes deciphered through phylogenetic network analysis

The primate ABO blood group gene encodes a glycosyl transferase (either A or B type), and is known to have large coalescence times among the allelic lineages in human. We determined nucleotide sequences of ca. 2.2 kb of this gene for 23 individuals of three gibbon species (agile gibbon, white-handed gibbon, and siamang), and observed a total of 24 haplotypes. We found relics of five ancient intragenic recombinations, occurred during ca. 2–7 million years ago, through a phylogenetic network analysis. The coalescence time between A and B alleles estimate precede the divergence (ca. 8 MYA) of siamang and common gibbon lineages. This establishes the coexistence of divergent allelic lineages of the ABO blood group gene for a long period in the ancestral gibbon species, and strengthens the non-neutral evolution for this gene.     

Potential merger of ancient lineages in a passerine bird discovered based on evidence from host‐specific ectoparasites

The merger of formerly isolated lineages is hypothesized to occur in vertebrates under certain conditions. However, despite many demonstrated instances of introgression between taxa in secondary contact, examples of lineage mergers are rare. Preliminary mtDNA sequencing of a Malagasy passerine, Xanthomixis zosterops (Passeriformes: Bernieridae), indicated a possible instance of merging lineages. We tested the hypothesis that X. zosterops lineages are merging by comparing mtDNA sequence and microsatellite data, as well as mtDNA sequence data from host‐specific feather lice in the genus Myrsidea (Phthiraptera: Menoponidae). Xanthomixis zosterops comprises four deeply divergent, broadly sympatric, cryptic mtDNA clades that likely began diverging approximately 3.6 million years ago. Despite this level of divergence, the microsatellite data indicate that the X. zosterops mtDNA clades are virtually panmictic. Three major phylogroups of Myrsidea were found, supporting previous allopatry of the X. zosterops clades. In combination, the datasets from X. zosterops and its Myrsidea document a potential merger of previously allopatric lineages that likely date to the Pliocene. This represents the first report of sympatric apparent hybridization among more than two terrestrial vertebrate lineages. Further, the mtDNA phylogeographic pattern of X. zosterops, namely the syntopy of more than two deeply divergent cryptic clades, appears to be a novel scenario among vertebrates. We highlight the value of gathering multiple types of data in phylogeographic studies to contribute to the study of vertebrate speciation.     

Phylogeography,more than elevation,accounts for sex chromosome differentiation in Swiss populations of the common frog (Rana temporaria)*

Sex chromosomes in vertebrates range from highly heteromorphic (as in most birds and mammals) to strictly homomorphic (as in many fishes, amphibians, and nonavian reptiles). Reasons for these contrasted evolutionary trajectories remain unclear, but species such as common frogs with polymorphism in the extent of sex chromosome differentiation may potentially deliver important clues. By investigating 92 common frog populations from a wide range of elevations throughout Switzerland, we show that sex chromosome differentiation strongly correlates with alleles at the candidate sex-determining gene Dmrt1. Y-specific Dmrt1 haplotypes cluster into two main haplogroups, Y_A and Y_B, with a phylogeographic signal that parallels mtDNA haplotypes: Y_A populations, with mostly well-differentiated sex chromosomes, occur primarily south of the main alpine ridge that bisects Switzerland, whereas Y_B populations, with mostly undifferentiated (proto-)sex chromosomes, occur north of this ridge. Elevation has only a marginal effect, opposing previous suggestions of a major role for climate on sex chromosome differentiation. The Y-haplotype effect might result from differences in the penetrance of alleles at the sex-determining locus (such that sex reversal and ensuing X-Y recombination are more frequent in Y_B populations), and/or fixation of an inversion on Y_A (as supported by the empirical observation that Y_A haplotypes might not recombine in XY_A females).     

Geographic ranges, population structure, and ages of sexual and parthenogenetic snail lineages

Abstract A sexual reproduction is thought to doom organisms to extinction due to mutation accumulation and parasite exploitation. Theoretical models suggest that parthenogens may escape the negative effects of conspecific and biological enemiecs through escape in space. Through intensive sequencing of a mitochondrial DNA (mtDNA) and a nuclear intron locus in sexual and pathenogenetic freshwater snails (Campelom), I examine three questionss: (1) Are sexual mtDNA lineage more restricted geographically than parthenogenetic mtDNA lineages? (2) Are independent pathenogenetic lineages shorter lived than sexual lineages? (3) Do pathenogens have higher intraindividual nuclear sequence diversity and form well‐differentiated monophyletic groups as expected under the Meselson effect? Geographic ranges of parthenogenetic lineages are significantly larger than geographic ranges of sexual lineages. Based on coalescence times under different deographic assumptions, asexual lineages are short lived, but there is variation in clonal ages. Although alternative explanations exit, these results suggest that asexual lineages may persist in the short term through dispersal, and that various constraints may cause geographic restriction of sexual lineagess. Both allotriploid and diploid Campleloma parthenogens have significantly higher allelic divergence within individuals, but show limited nuclear sequence divergence from sexual ancestors. In contrast to previous allozyme evidence for nonhybrid origins of diploid Campeloma parthenogens, cryptic hybridization may account for elevated heterozygosity.     

Mitochondrial DNA diversity and taxa delineation in the land snails of the Iberus gualtieranus (Pulmonata,Helicidae) complex

Iberus gualtieranus is a species complex of land snails that is endemic to the Iberian Peninsula. The species taxonomy of the group is based merely on the basis of shell morphology, but validity of the existing taxonomy is uncertain. Using mitochondrial DNA (mtDNA) data (cytochrome oxidase I and 16S rRNA sequences) we were able to validate the observed phylogenetic taxa within the I. gualtieranus s.l. complex by means of the analysis of specimens of the different morphospecies, together with the study of topotypes. Strong incongruences were obtained between morphology and molecular data. The Iberus alonensis morphospecies comprised several genetically divergent but morphologically cryptic lineages. Considering (1) the allopatric distribution of the operational taxonomic units (OTUs), (2) the morphological differentiation, (3) the possible occurrence of hybridization among the different lineages, and (4) the strong differentiation of the mtDNA phylogroups, we suggest the main lineages obtained, for the time being, may be treated as evolutionary species. The robust phylogenetic reconstruction obtained allows us to consider I. alonensis s.s., Iberus campesinus, Iberus carthaginiensis, and Iberus gualtieranus s.s. as valid species. Two additional unnominated taxa of the alonensis shell type have also been identified. Further subdivisions are also considered, including Iberus gualtieranus mariae and Iberus gualtieranus ornatissimus. © 2008 The Linnean Society of London, Zoological Journal of the Linnean Society, 2008, 154 , 722–737.     

Biogeography of ‘Cyprinella lutrensis’: intensive genetic sampling from the Pecos River ‘melting pot’ reveals a dynamic history and phylogenetic complexity

Thorough sampling is necessary to delineate lineage diversity for polytypic ‘species’ such as Cyprinella lutrensis. We conducted extensive mtDNA sampling (cytochrome b and ND4) from the Pecos River, Rio Grande, and South Canadian River, New Mexico. Our study focussed on the Pecos River due to its complex geological history and potential to harbour multiple lineages. We used geometric–morphometric, morphometric, and meristic analyses to test for phenotypic divergence and combined nucDNA with mtDNA to test for cytonuclear disequilibrium and combined our sequences with published data to conduct a phylogenetic re‐assessment of the entire C. lutrensis clade. We detected five co‐occurring mtDNA lineages in the Pecos River, but no evidence for cytonuclear disequilibrium or phenotypic divergence. Recognized species were interspersed amongst divergent lineages of ‘C. lutrensis’. Allopatric divergence among drainages isolated in the Late Miocene and Pliocene apparently produced several recognized species and major divisions within ‘C. lutrensis’. Pleistocene re‐expansion and subsequent re‐fragmentation of a centralized lineage founded younger, divergent lineages throughout the Rio Grande basin and Edwards Plateau. There is also evidence of recent introductions to the Rio Grande, Pecos and South Canadian Rivers. Nonetheless, deeply divergent lineages have coexisted since the Pleistocene.     

Conservation genetics of the black rhinoceros (Diceros bicornis)

We analysed genetic variation in mitochondrial DNA (mtDNA) control region in the Diceros bicornis minor and D. b. michaelianimals at the Western Plains Zoo, which form part of an international ex-situ breeding program. Six of the nine D. b. minor animals were wild-caught from Zimbabwe during the 1990s, and our study revealed five distinct mtDNA haplotypes, and a haplotype diversity of 0.86 in the colony. Phylogenetic relationships between mtDNA haplotypes analyzed using the neighbor joining method reveal that for the small sample available, D. b. minor and D. b. michaeli are reciprocally monophyletic and represent separate ancestral lineages. Nucleotide divergence between the black and and white rhinoceros(Ceratotherium simum) was 14.0%, and nucleotide divergencebetween the D. b. minor and the D. b. michaeli subspecies was 2.6%. This suggests a divergence time for the two blackrhinoceros subspecies of between 0.93 MY and 1.3 MY.     

Female-to-Male Breeding Ratio in Modern Humans—an Analysis Based on Historical Recombinations

Was the past genetic contribution of women and men to the current human population equal? Was polygyny (excess of breeding women) present among hominid lineages? We addressed these questions by measuring the ratio of population recombination rates between the X chromosome and the autosomes, ρ_X/ρ_A. The X chromosome recombines only in female meiosis, whereas autosomes undergo crossovers in both sexes; thus, ρ_X/ρ_A reflects the female-to-male breeding ratio, β. We estimated β from ρ_X/ρ_A inferred from genomic diversity data and calibrated with recombination rates derived from pedigree data. For the HapMap populations, we obtained β of 1.4 in the Yoruba from West Africa, 1.3 in Europeans, and 1.1 in East Asian samples. These values are consistent with a high prevalence of monogamy and limited polygyny in human populations. More mutations occur during male meiosis as compared to female meiosis at the rate ratio referred to as α. We show that at α ≠ 1, the divergence rates and genetic diversities of the X chromosome relative to the autosomes are complex functions of both α and β, making their independent estimation difficult. Because our estimator of β does not require any knowledge of the mutation rates, our approach should allow us to dissociate the effects of α and β on the genetic diversity and divergence rate ratios of the sex chromosomes to the autosomes.     

Thirty allele-level haplotypes centered around KIR2DL5 define the diversity in an African American population

KIR2DL5 alleles were physically linked to alleles at adjacent KIR loci to define this region of KIR haplotypes in 55 gene-positive random African Americans. The majority carried KIR2DL5B. Three KIR2DL5A and six KIR2DL5B alleles that have been previously described and 11 novel KIR2DL5 alleles were identified by DNA sequencing. Novel alleles included variation that may impact promoter activity; two alleles carried nonsynonymous coding region variation. Based on linkage with KIR2DS1, KIR2DS3, KIR2DS5, KIR2DL2, KIR2DL3, and KIR3DS1 alleles, seven haplotypes of KIR2DL5A and 23 haplotypes of KIR2DL5B were observed. The phylogenetic relationships among the KIR2DL5 alleles predicted their association with either KIR2DS3 (six alleles) or KIR2DS5 (seven alleles). All of the KIR2DL5A alleles were linked either to KIR3DS1*01301 or KIR3DS1*049N. The majority of the KIR2DL5B alleles were linked to seven KIR2DL2 alleles; two were linked to a novel allele of KIR2DL3. These findings underscore the diversity of KIR haplotypes present in this population.