Signatures of positive selection in genes associated with human skin pigmentation as revealed from analyses of single nucleotide polymorphisms.

Phenotypic variation between human populations in skin pigmentation correlates with latitude at the continental level. A large number of hypotheses involving genetic adaptation have been proposed to explain human variation in skin colour, but only limited genetic evidence for positive selection has been presented. To shed light on the evolutionary genetic history of human variation in skin colour we inspected 118 genes associated with skin pigmentation in the Perlegen dataset, studying single nucleotide polymorphisms (SNPs), and analyzed 55 genes in detail. We identified eight genes that are associated with the melanin pathway (SLC45A2, OCA2, TYRP1, DCT, KITLG, EGFR, DRD2 and PPARD) and presented significant differences in genetic variation between Europeans, Africans and Asians. In six of these genes we detected, by means of the EHH test, variability patterns that are compatible with the hypothesis of local positive selection in Europeans (OCA2, TYRP1 and KITLG) and in Asians (OCA2, DCT, KITLG, EGFR and DRD2), whereas signals were scarce in Africans (DCT, EGFR and DRD2). Furthermore, a statistically significant correlation between genotypic variation in four pigmentation candidate genes and phenotypic variation of skin colour in 51 worldwide human populations was revealed. Overall, our data also suggest that light skin colour is the derived state and is of independent origin in Europeans and Asians, whereas dark skin color seems of unique origin, reflecting the ancestral state in humans.

Morphological variability within Oesophagostomum bifurcum among different primate species from Ghana.

Adult Oesophagostomum bifurcum (Nematoda: Strongylida) from human and non-human primates from Ghana were compared in order to investigate the extent of morphological variability within the species. Using analysis of variance and principal component analysis, significant differences in morphological characters (such as parasite length, width, length of the oesophagus and length of spicules) were demonstrated between O. bifurcum worms from humans, the Mona, Patas or Green monkey and/or Olive baboons. These findings suggest that O. bifurcum from different species of primate host represent distinct population variants, also supported by recent epidemiological and genetic studies of O. bifurcum from such hosts.

Insights into the epidemiology and genetic make-up of Oesophagostomum bifurcum from human and non-human primates using molecular tools.

The nodule worm Oesophagostomum bifurcum (Nematoda: Strongylida) is a parasite of major human health importance predominantly in northern Togo and Ghana. Currently, it is estimated that 0.25 million people are infected with this nematode, and at least 1 million people are at risk of infection. Infection with this parasite causes significant disease as a consequence of encysted larvae in the wall of the large intestine. In spite of the health problems caused by O. bifurcum, there have been significant gaps in the knowledge of the biology, transmission and population genetics of the parasite. This review provides an account of some recent insights into the epidemiology and genetics of the parasite from human and non-human primate hosts in specific regions of Africa using molecular tools. Recent research findings are discussed mainly in relation to non-human primates being reservoirs of infection, and the consequences for the prevention and control of oesophagostomiasis in humans are briefly discussed.

Definition of genetic markers in nuclear ribosomal DNA for a neglected parasite of primates, Ternidens deminutus (Nematoda: Strongylida)--diagnostic and epidemiological implications.

Ternidens deminutus (Strongylida) is a parasitic nematode infecting non-human and human primates in parts of Africa, Asia and the Pacific islands. The present study genetically characterized T. deminutus and defined genetic markers in nuclear ribosomal DNA (rDNA) as a basis for developing molecular-diagnostic tools. The sequences of the second internal transcribed spacer (ITS-2) of rDNA were determined for adult specimens of T. deminutus (Nematoda: Strongylida: Oesophagostominae) from the Olive baboon and the Mona monkey. The length and G+C content of the ITS-2 sequences was 216 bp and approximately 43%, respectively. While there was no sequence variation among individual T. deminutus specimens from the baboon, 6 (2.8%) nucleotide differences were detected in the ITS-2 between the parasite from baboon and that of the Mona monkey, which is similar to the difference (3.2%) between 2 other species of Oesophagostominae (Oesophagostomum bifurcum and O. stephanostomum) from non-human primates, suggesting significant population variation or the existence of cryptic (i.e. hidden) species within T. deminutus . Pairwise comparisons of the ITS-2 sequences of the 2 operational taxonomic units of T. deminutus with previously published ITS-2 sequences for selected members of the subfamilies Oesophagostominae and Chabertiinae indicated that species from primates (including those representing the subgenera Conoweberia and Ihleia) are closely related, in accordance with previous morphological studies. The sequence differences (27-48.3%) in the ITS-2 between the 2 taxonomic units of T. deminutus and hookworms (superfamily Ancylostomatoidea) enabled their identification and delineation by polymerase chain reaction (PCR)-based mutation scanning. The genetic markers in the ITS-2 provide a foundation for improved, PCR-based diagnosis of T. deminutus infections and for investigating the life-cycle, transmission patterns and ecology of this parasite.

High resolution DNA fingerprinting by AFLP to study the genetic variation among Oesophagostomum bifurcum (Nematoda) from human and non-human primates from Ghana.

An AFLP approach was established to investigate genetic diversity within Oesophagostomum bifurcum (order Strongylida) from human and non-human primates. Evaluation of different combinations of restriction enzymes (n = 8) and primers (n = 29) demonstrated that the use of HindIII/BglII digested templates and primers with the selective nucleotides + AG/ +AC, respectively, was the most effective for the analysis of O. bifurcum DNA. A total of 63 O. bifurcum adults from human, Patas monkey, Mona monkey and Olive baboon hosts from different geographical regions in Ghana were subjected to analysis using this method. Cluster analysis revealed 4 genetically distinct groups, namely O. bifurcum from the Patas monkey (I), from the Mona monkey (II), from humans (III) and from the Olive baboon (IV). These findings were concordant with those achieved previously using RAPD analysis and supports population genetic substructuring within O. bifurcum according to host species. The results demonstrated the effectiveness of the present AFLP method for establishing genetic variation within O. bifurcum, and indicates its applicability to other parasitic nematodes of human and/or veterinary health importance.

Screening for haplotypic variability within Oesophagostomum bifurcum (Nematoda) employing a single-strand conformation polymorphism approach.

Genetic markers in the mitochondrial genome have proven useful for population genetic studies because of their maternal inheritance and relatively high evolutionary rates. In this study, we exploited the high resolution capacity of PCR-coupled single-strand conformation polymorphism (SSCP) to screen for sequence variation in part of the cytochrome c oxidase subunit 1 gene (p cox 1) among individuals of the parasitic nematode, Oesophagostomum bifurcum from human or Mona monkey hosts from Africa. SSCP analysis revealed distinct profiles among some of the individuals, and subsequent sequence analysis of representative samples defined 10 different haplotypes. For comparative purposes, the p cox 1 sequences for representatives of four other species of Oesophagostomum from livestock were included. While there were high levels (11.5-13.7%) of sequence difference among the latter species, there was no fixed nucleotide difference between O. bifurcum individuals from humans and those from monkeys. The data support the proposal that O. bifurcum from the two primate hosts represents a single species and that the haplotypic variability in p cox 1 represents population variation. The results reinforce the usefulness of the SSCP-sequencing approach for studying genetic variation in nematode populations using mitochondrial markers.