Common HLA Alleles Associated with Health, but Not with Facial Attractiveness

Three adaptive hypotheses have been proposed to explain the link between the human leucocyte antigen (HLA) genes, health measures and facial attractiveness: inbreeding avoidance, heterozygote advantage and frequency-dependent selection. This paper reports findings that support a new hypothesis relating HLA to health. We suggest a new method to quantify the level of heterozygosity. HLA heterozygosity did not significantly predict health measures in women, but allele frequency did. Women with more common HLA alleles reported fewer cold and flu bouts per year, fewer illnesses in the previous year and rated themselves healthier than women with rare alleles. To our knowledge, this is the first study to show a positive correlation between HLA allele frequency and general health measures. We propose that certain common HLA alleles confer resistance to prevalent pathogens. Nevertheless, neither HLA heterozygosity nor allele frequency significantly predicted how healthy or attractive men rated the female volunteers. Three non-mutually exclusive explanations are put forward to explain this finding

Systems Biology Approaches Reveal a Specific Interferon-Inducible Signature in HTLV-1 Associated Myelopathy

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that persists lifelong in the host. In ∼4% of infected people, HTLV-1 causes a chronic disabling neuroinflammatory disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The pathogenesis of HAM/TSP is unknown and treatment remains ineffective. We used gene expression microarrays followed by flow cytometric and functional assays to investigate global changes in blood transcriptional profiles of HTLV-1-infected and seronegative individuals. We found that perturbations of the p53 signaling pathway were a hallmark of HTLV-1 infection. In contrast, a subset of interferon (IFN)-stimulated genes was over-expressed in patients with HAM/TSP but not in asymptomatic HTLV-1 carriers or patients with the clinically similar disease multiple sclerosis. The IFN-inducible signature was present in all circulating leukocytes and its intensity correlated with the clinical severity of HAM/TSP. Leukocytes from patients with HAM/TSP were primed to respond strongly to stimulation with exogenous IFN. However, while type I IFN suppressed expression of the HTLV-1 structural protein Gag it failed to suppress the highly immunogenic viral transcriptional transactivator Tax. We conclude that over-expression of a subset of IFN-stimulated genes in chronic HTLV-1 infection does not constitute an efficient host response but instead contributes to the development of HAM/TSP

Avian β-defensin variation in bottlenecked populations : the Seychelles warbler and other congeners

β-defensins are important components of the vertebrate innate immune system responsible for encoding a variety of anti-microbial peptides. Pathogen-mediated selection is thought to act on immune genes and potentially maintain allelic variation in the face of genetic drift. The Seychelles warbler, Acrocephalus sechellensis, is an endemic passerine that underwent a recent bottleneck in its last remaining population, resulting in a considerable reduction in genome-wide variation. We genotyped avian β-defensin (AvBD) genes in contemporary (2000–2008) and museum samples (1876–1940) of the Seychelles warbler to investigate whether immunogenetic variation was lost through this bottleneck, and examined AvBD variation across four other Acrocephalus species with varying demographic histories. No variation was detected at four of the six AvBD loci screened in the post-bottleneck population of Seychelles warbler, but two silent nucleotide polymorphisms were identified at AvBD8 and one potentially functional amino-acid variation was observed at AvBD11. Variation in the Seychelles warbler was significantly lower than in the mainland migratory congeneric species investigated, but it similar to that found in other bottlenecked species. In addition, screening AvBD7 in 15 museum specimens of Seychelles warblers sampled prior to the bottleneck (1877–1905) revealed that this locus possessed two alleles previously, compared to the single allele in the contemporary population. Overall, the results show that little AvBD variation remains in the Seychelles warbler, probably as a result of having low AvBD diversity historically rather than the loss of variation due to drift associated with past demographic history. Given the limited pathogen fauna, this lack of variation at the AvBD loci may currently not pose a problem for this isolate population of Seychelles warblers, but it may be detrimental to the species’ long-term survival if new pathogens reach the population in the future

Contrasting responses to selection in class I and class II alpha major histocompatibility-linked markers in salmon

Comparison of levels and patterns of genetic variation in natural populations either across loci or against neutral expectation can yield insight into locus-specific differences in the strength and direction of evolutionary forces. We used both approaches to test the hypotheses on patterns of selection on major histocompatibility (MH)-linked markers. We performed temporal analyses of class I and class IIα MH-linked markers and eight microsatellite loci in two Atlantic salmon populations in Ireland on two temporal scales: over six decades and 9 years in the rivers Burrishoole and Delphi, respectively. We also compared contemporary Burrishoole and Delphi samples with nearby populations for the same loci. On comparing patterns of temporal and spatial differentiation among classes of loci, the class IIα MH-linked marker was consistently identified as an outlier compared with patterns at the other microsatellite loci or neutral expectation. We found higher levels of temporal and spatial heterogeneity in heterozygosity (but not in allelic richness) for the class IIα MH-linked marker compared with microsatellites. Tests on both within- and among-population differentiation are consistent with directional selection acting on the class IIα-linked marker in both temporal and spatial comparisons, but only in temporal comparisons for the class I-linked marker. Our results indicate a complex pattern of selection on MH-linked markers in natural populations of Atlantic salmon. These findings highlight the importance of considering selection on MH-linked markers when using these markers for management and conservation purposes