Biology subjects

Shigeki Nakagome

Publications and source records attributed to Shigeki Nakagome.

3 recordsLinked to original sources

bioRxiv2016

Demographic and immune-based selection shifts before and after European contact inferred from 50 ancient and modern exomes from the Northwest Coast of North America

The susceptibility of Native Americans to infectious disease has been postulated as a major factor for their population decline after European contact. To investigate if a preexisting genetic component contributed to this phenomenon, we analyzed 50 exomes of both ancient and modern individuals from the Northwest Coast of North America, dating from before and after European contact. We confirmed the genetic continuity between the ancient and modern individuals and modeled the population collapse after European contact, inferring a 57% reduction in effective population size. We also identified signatures of positive selection on immune-related genes in the ancient but not the modern group. The strongest selection signal in the ancients came from the human leukocyte antigen (HLA) gene HLA-DQA1, with alleles that are close to fixation. The important immune function of HLA-DQA1 supports an ancient adaptation to the environments of the Americas. The modern individuals show a marked decrease in the frequency of the associated alleles (the most pronounced variant showing a 64% difference). This decrease is likely due to the environmental change associated with European colonization, which resulted in a shift of selection pressures, whereby negative selection may have acted on the same gene after contact. Furthermore, the selection pressure shift could correlate to the European-borne epidemics of the 1800s, suffered in the Northwest Coast region. This is among the first studies to examine a single population through time and exemplifies the power of such studies in uncovering nuanced demographic and adaptive histories.

Genetics↗

bioRxiv2015

Patterns of transcriptional response to 1,25-dihydroxyvitamin D3 and bacterial lipopolysaccharide in primary human monocytes

The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), plays an important immunomodulatory role, regulating transcription of genes in the innate and adaptive immune system. The present study examines patterns of transcriptome-wide response to 1,25D and the bacterial lipopolysaccharide (LPS) in primary human monocytes, to elucidate pathways underlying the effects of 1,25D on the immune system. Monocytes obtained from healthy individuals of African-African and European-American ancestry were treated with 1,25D alone or in the presence of LPS, which induced significant up-regulation of genes in the antimicrobial and autophagy pathways, while pro-inflammatory response genes were significantly down-regulated. A joint Bayesian analysis enabled clustering of genes into patterns of shared transcriptional response across treatments. The biological pathways enriched within these expression patterns highlighted several mechanisms through which 1,25D could exert its immunomodulatory role. Pathways such as mTOR signaling, EIF2 signaling, IL-8 signaling and Tec Kinase signaling were enriched among genes with opposite transcriptional responses to 1,25D and LPS, respectively, highlighting the important roles of these pathways in mediating the immunomodulatory activity of 1,25D. Furthermore, a subset of genes with evidence of inter-ethnic differences in transcriptional response was also identified, suggesting that in addition to the well-established inter-ethnic variation in circulating levels of vitamin D, the intensity of transcriptional response to 1,25D and LPS also varies between ethnic groups. We propose that dysregulation of the pathways identified in this study could contribute to immune-mediated disease risk.

Genetics↗

bioRxiv2013

Natural Allelic Variations of Xenobiotic Enzymes Pleiotropically Affect Sexual Dimorphism in Oryzias latipes

Summary Summary Highlights Results and Discussion Accession Numbers Reference Sexual dimorphisms, which are phenotypic differences between males and females, are driven by sexual selection [1, 2]. Interestingly, sexually selected traits show geographic variations within species despite strong directional selective pressures [3, 4]. However, genetic factors that regulate varied sexual differences remain unknown. In this study, we show that polymorphisms in cytochrome P450 (CYP) 1B1, which encodes a xenobiotic-metabolising enzyme, are associated with local differences of sexual dimorphisms in the anal fin morphology of medaka fish (Oryzias latipes). High and low activity CYP1B1 alleles increased and decreased differences in anal fin sizes ...

Evolutionary Biology↗