中生動物ニハイチュウの発生初期におけるDNA再配列と増幅を示唆する環状DNA群の出現と消失

取得学位：博士(理学)，学位授与番号：博甲第550号，学位授与年月日：平成15年3月25日,学位授与年：200

Structure of the germline genome of Tetrahymena thermophila and relationship to the massively rearranged somatic genome

The germline genome of the binucleated ciliate Tetrahymena thermophila undergoes programmed chromosome breakage and massive DNA elimination to generate the somatic genome. Here, we present a complete sequence assembly of the germline genome and analyze multiple features of its structure and its relationship to the somatic genome, shedding light on the mechanisms of genome rearrangement as well as the evolutionary history of this remarkable germline/soma differentiation. Our results strengthen the notion that a complex, dynamic, and ongoing interplay between mobile DNA elements and the host genome have shaped Tetrahymena chromosome structure, locally and globally. Non-standard outcomes of rearrangement events, including the generation of short-lived somatic chromosomes and excision of DNA interrupting protein-coding regions, may represent novel forms of developmental gene regulation. We also compare Tetrahymenas germline/soma differentiation to that of other characterized ciliates, illustrating the wide diversity of adaptations that have occurred within this phylum.</p

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Whats, hows and whys of programmed DNA elimination in Tetrahymena

International audienc

Small RNA-Mediated trans -Nuclear and trans -Element Communications in Tetrahymena DNA Elimination

International audienceEpigenetic inheritance of acquired traits is widespread among eukaryotes, but how and to what extent such information is transgenerationally inherited is still unclear. The patterns of programmed DNA elimination in ciliates are epigenetically and transgenerationally inherited, and it has been proposed that small RNAs, which shuttle between the germline and the soma, regulate this epigenetic inheritance. In this study, we test the existence and role of such small-RNA-mediated communication by epigenetically disturbing the pattern of DNA elimination in Tetrahymena. We show that the pattern of DNA elimination is, indeed, determined by the selective turnover of small RNAs, which is induced by the interaction between germline-derived small RNAs and the somatic genome. In addition, we show that DNA elimination of an element is regulated by small-RNA-mediated communication with other eliminated elements. By contrast, no evidence obtained thus far supports the notion that transfer of epigenetic information from the soma to the germline, if any, regulates DNA elimination. Our results indicate that small-RNA-mediated trans-nuclear and trans-element communication, in addition to unknown information in the germline genome, contributes to determining the pattern of DNA elimination

Diversification of small RNA amplification mechanisms for targeting transposon-related sequences in ciliates

International audienc

Peculiar behavior of distinct chromosomal DNA elements during and after development in the dicyemid mesozoan Dicyema japonicum

The dicyemid mesozoans are obligate parasites that inhabit the cephalopod renal appendage. Dicyemids have a simple body, consisting of approximately 30 cells: one long cylindrical axial cell contains intracellular stem cells (called axoblast), from which embryos are derived, and is surrounded by some 30 peripheral somatic cells. Somatic cells divide at most eight times in their life span, and never divide after differentiation. During early somatic cell development, numerous unique DNA sequences are first amplified and then eliminated, in the form of extrachromosomal circular DNA, leading to genome reduction. In this study we demonstrate that the remaining sequences, single-copy genes and repetitive sequences, have very different fates. Single-copy genes, such as β-tubulin, are initially amplified, presumably via endoreduplication, but subsequently decrease in copy number through development, suggesting that the whole genome is initially amplified and then the amplified DNAs are simply diluted in successive cell divisions, with little DNA replication. In contrast, repetitive sequences are maintained even in terminally differentiated somatic cell nuclei. Considering the increasing intensity of in-situ hybridization, incorporation of BrdU, and a general correlation between nuclear content and cell size, those repetitive sequences must be selectively endoreplicated in the peripheral cell nucleus, concomitant with the increase of cell size. The biological significance of this mechanism is discussed as a unique dicyemid adaptation to parasitism