Lineage-specific positive selection at the merozoite surface protein 1 (msp1) locus of Plasmodium vivax and related simian malaria parasites

<p>Abstract</p> <p>Background</p> <p>The 200 kDa merozoite surface protein 1 (MSP-1) of malaria parasites, a strong vaccine candidate, plays a key role during erythrocyte invasion and is a target of host protective immune response. <it>Plasmodium vivax</it>, the most widespread human malaria parasite, is closely related to parasites that infect Asian Old World monkeys, and has been considered to have become a parasite of man by host switch from a macaque malaria parasite. Several Asian monkey parasites have a range of natural hosts. The same parasite species shows different disease manifestations among host species. This suggests that host immune responses to <it>P. vivax</it>-related malaria parasites greatly differ among host species (albeit other factors). It is thus tempting to invoke that a major immune target parasite protein such as MSP-1 underwent unique evolution, depending on parasite species that exhibit difference in host range and host specificity.</p> <p>Results</p> <p>We performed comparative phylogenetic and population genetic analyses of the gene encoding MSP-1 (<it>msp1</it>) from <it>P. vivax </it>and nine <it>P. vivax</it>-related simian malaria parasites. The inferred phylogenetic tree of <it>msp1 </it>significantly differed from that of the mitochondrial genome, with a striking displacement of <it>P. vivax </it>from a position close to <it>P. cynomolgi </it>in the mitochondrial genome tree to an outlier of Asian monkey parasites. Importantly, positive selection was inferred for two ancestral branches, one leading to <it>P. inui </it>and <it>P. hylobati </it>and the other leading to <it>P. vivax</it>, <it>P. fieldi </it>and <it>P. cynomolgi</it>. This ancestral positive selection was estimated to have occurred three to six million years ago, coinciding with the period of radiation of Asian macaques. Comparisons of <it>msp1 </it>polymorphisms between <it>P. vivax</it>, <it>P. inui </it>and <it>P. cynomolgi </it>revealed that while some positively selected amino acid sites or regions are shared by these parasites, amino acid changes greatly differ, suggesting that diversifying selection is acting species-specifically on <it>msp1</it>.</p> <p>Conclusions</p> <p>The present results indicate that the <it>msp1 </it>locus of <it>P. vivax </it>and related parasite species has lineage-specific unique evolutionary history with positive selection. <it>P. vivax </it>and related simian malaria parasites offer an interesting system toward understanding host species-dependent adaptive evolution of immune-target surface antigen genes such as <it>msp1</it>.</p

Analysis of whole Y-chromosome sequences reveals the Japanese population history in the Jomon period

UTokyo FOCUS Press releases "Archaeological mystery solved with modern genetics : Y chromosomes reveal population boom and bust in ancient Japan" https://www.u-tokyo.ac.jp/focus/en/press/z0508_00056.htm

Discerning the origins of the Negritos, First Sundaland People : deep divergence and archaic admixture

Human presence in Southeast Asia dates back to at least40,000 years ago, when the current islands for meda continental shelf called Sundaland. In the Philippine Islands, Peninsular Malaysia, and Andaman Islands, there exist indigenous groups collectively called Negritos whose ancestry can be traced to the “First Sundaland People.” To understand the relationship between these Negrito groupsand theirdemographic histories, wegeneratedgenome-wide single nucleotide polymorphism datain the Philippine Negritos and compared them with existing data from other populations. Phylogenetic tree analyses show that Negritos are basal to other East and Southeast Asians, and that they diverged from West Eurasians at least 38,000 years ago. We also found relatively high traces of Denisovan admixture in the Philippine Negritos, but not in the Malaysian and Andamanese groups, suggesting independent introgression and/or parallel losses involving Denisovan introgressed regions. Shared genetic loci between all three Negrito groups could be related to skin pigmentation, height, facial morphology and malarial resistance. These results show the unique status of Negrito groups as descended from the First Sundaland People

A human PSMB11 variant affects thymoproteasome processing and CD8+ T cell production

The Psmb11-encoded β5t subunit of the thymoproteasome, which is specifically expressed in cortical thymic epithelial cells (cTECs), is essential for the optimal positive selection of functionally competent CD8+ T cells in mice. Here, we report that a human genomic PSMB11 variation, which is detectable at an appreciable allele frequency in human populations, alters the β5t amino acid sequence that affects the processing of catalytically active β5t proteins. The introduction of this variation in the mouse genome revealed that the heterozygotes showed reduced β5t expression in cTECs and the homozygotes further exhibited reduction in the cellularity of CD8+ T cells. No severe health problems were noticed in many heterozygous and 5 homozygous human individuals. Long-term analysis of health status, particularly in the homozygotes, is expected to improve our understanding of the role of the thymoproteasome-dependent positive selection of CD8+ T cells in humans

The Origin and Genetic Variation of Domestic Chickens with Special Reference to Junglefowls Gallus g. gallus and G. varius

It is postulated that chickens (Gallus gallus domesticus) became domesticated from wild junglefowls in Southeast Asia nearly 10,000 years ago. Based on 19 individual samples covering various chicken breeds, red junglefowl (G. g. gallus), and green junglefowl (G. varius), we address the origin of domestic chickens, the relative roles of ancestral polymorphisms and introgression, and the effects of artificial selection on the domestic chicken genome. DNA sequences from 30 introns at 25 nuclear loci are determined for both diploid chromosomes from a majority of samples. The phylogenetic analysis shows that the DNA sequences of chickens, red and green junglefowls formed reciprocally monophyletic clusters. The Markov chain Monte Carlo simulation further reveals that domestic chickens diverged from red junglefowl 58,000±16,000 years ago, well before the archeological dating of domestication, and that their common ancestor in turn diverged from green junglefowl 3.6 million years ago. Several shared haplotypes nonetheless found between green junglefowl and chickens are attributed to recent unidirectional introgression of chickens into green junglefowl. Shared haplotypes are more frequently found between red junglefowl and chickens, which are attributed to both introgression and ancestral polymorphisms. Within each chicken breed, there is an excess of homozygosity, but there is no significant reduction in the nucleotide diversity. Phenotypic modifications of chicken breeds as a result of artificial selection appear to stem from ancestral polymorphisms at a limited number of genetic loci

Genome-Wide Association Study Confirming Association of HLA-DP with Protection against Chronic Hepatitis B and Viral Clearance in Japanese and Korean

Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85–90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with Pmeta = 1.89×10−12 for rs3077 and Pmeta = 9.69×10−10 for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB) in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (Pmeta = 4.40×10−19 for rs3077 and Pmeta = 1.28×10−15 for rs9277542). These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule

Evolutionary Relationships of Major Histocompatibility Complex Class I Genes in Similar Primates

　　　Major histocompatibility complex (MHC) genes code for glycoproteins that can trigger the so- called acquired immune system by presenting non-self peptides to T cells. MHC class I genes evolved with rapid gene duplications and turnover. Indeed, comparative studies of marsupial and eutherian MHC class I genes have shown that the two mammalian subclasses express MHC class I genes of different evolutionary lineages. Furthermore, orthologous relationships have not been established among MHC class I genes of different mammalian orders, such as rodents, primates and so on. Until now, this also holds true even within primates, and New World monkeys (NWMs) occupy a critical phylogenetic position in elucidating the evolutionary process of MHC class I genes in primates. Although there have been many studies about primate MHC evolution, almost all studies have concentrated on humans, apes and Old World monkeys. These studies have revealed some orthologous relationships, but not with NWMs. To reconstruct the evolutionary history of primate MHC class I genes, it is imperative to examine NWMs.　　　In outer to understand the evolutionary dynamics of primate MHC class I genes, the orthologous relationships of various MHC genes, particularly B and G related or group B and G genes, were examined in three species of NWMs. The 5\u27 flanking region of class I genes was used in the analysis because this region contains a number of phylogenetically informative insertion elements and numerous nucleotide substitutions. From three subfamilies of Aotinae, Cebinae and Atelinae, the 5\u27 flanking regions of 18 class I genes were obtained and phylogenetically examined in terms of their Alu/LINE insertion elements and nucleotide substitutions. Two pairs of genes from Aotinae and Atelinae are clearly orthologous to the HLA-E and -F genes. Among the remaining 14 genes, eight belong to a distinct group B, together with HLA-B and -C, but not with other HLA class I genes. These eight NWM genes are grouped into four, which are designated as NWM-Bl, -B2, -B3 and -B4. Of these, NWM-B2 is orthologous to HLA- B/C. Orthologous relationships of NWM-Bl, -B2 and -B3 are present between different families of Cebidae and Atelidae, which is in sharp contrast to the genus-spectfic gene organization within subfamily Callitrichinae. The other six genes belong to a distinct group G. However, a monophyletic clade of these six NWM genes is almost equally related to HLA-A, -J, -G or -K, and there is no strong support for their orthologous relationship to HLA-G. It is argued that class I genes in simian primates are extensively duplicated in their common ancestral lineage, and that their subsequent evolution in descendant species has been facilitated mainly by the independent loss of genes. 　　　Following on the above, DNA sequence data from HLA class I genes were analyzed, including pseudogenes, to estimate the time when previously functional HLA genes became pseudogenes. The functional cnstraint at nonsynonymous sites must have been relaxed since a HLA gene became a pseudogene. Using this change in functional constraint, I estimated the time of HLA pseudogenizaion. Four HLA pseudogenes (HLA-H, -J, -K and -L) were compared with functional HLA genes belonging to the most closely related groups (HLA-A, -G, -G and -B). The HLA dysfunctioning times were estimated as 1.3-6.6, 14.7-33.2, 36.6-45.9 and 46.2-46.6 million years (myr) ago for HLA-H, -J, -K and -L, respectively It is suggested that there have always been six to eight functional HLA genes at any given time during the past 50 myr. 　　　Finally, in order to explore the evolutionary trends of classical or nonclassical class I genes, I examined the HLA promoter region and peptide binding region (PBR), and discuss the functional changes of MHC class I genes in NWMs. The regulatory elements in HLA classical class I genes seem to be fairly well conserved On the other hand, nonclassical class I genes display nucleotide sequence variations when compared to sequences of classical class I gene promoters. Promoter sequence analysis of MHC genes of Aotus trivirgatus shows that Aotr-B1 and -B2 have nonclassical-like characteristics, and Aotr-B3, -G1 and - G2 have classical-like characteristics. Aotr-B1 lacks X2 and a TATA box, and Aotr-B2 lacks almost all transcription binding sites. In Aotr-G1 and -G2, all binding sites that are observed in classical class I genes are intact, whereas Aotr-B3 lacks only a TATA box. A phylogenetic analysis of PBRs supports the above characteristics. Consequently, it is suggested that there is no obvious relationship between the groups defined by phylogenetic analyses and the division of classical and nonclassical class I genes