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1.
Sci Rep ; 6: 39734, 2016 12 22.
Article in English | MEDLINE | ID: mdl-28004835

ABSTRACT

Despite half a century of research, the biology of dinoflagellates remains enigmatic: they defy many functional and genetic traits attributed to typical eukaryotic cells. Genomic approaches to study dinoflagellates are often stymied due to their large, multi-gigabase genomes. Members of the genus Symbiodinium are photosynthetic endosymbionts of stony corals that provide the foundation of coral reef ecosystems. Their smaller genome sizes provide an opportunity to interrogate evolution and functionality of dinoflagellate genomes and endosymbiosis. We sequenced the genome of the ancestral Symbiodinium microadriaticum and compared it to the genomes of the more derived Symbiodinium minutum and Symbiodinium kawagutii and eukaryote model systems as well as transcriptomes from other dinoflagellates. Comparative analyses of genome and transcriptome protein sets show that all dinoflagellates, not only Symbiodinium, possess significantly more transmembrane transporters involved in the exchange of amino acids, lipids, and glycerol than other eukaryotes. Importantly, we find that only Symbiodinium harbor an extensive transporter repertoire associated with the provisioning of carbon and nitrogen. Analyses of these transporters show species-specific expansions, which provides a genomic basis to explain differential compatibilities to an array of hosts and environments, and highlights the putative importance of gene duplications as an evolutionary mechanism in dinoflagellates and Symbiodinium.


Subject(s)
Adaptation, Biological/physiology , Anthozoa/physiology , Dinoflagellida/genetics , Evolution, Molecular , Genome , Symbiosis/physiology , Animals , Dinoflagellida/classification
2.
Sci Rep ; 6: 31326, 2016 08 09.
Article in English | MEDLINE | ID: mdl-27502179

ABSTRACT

The agricultural transition profoundly changed human societies. We sequenced and analysed the first genome (1.39x) of an early Neolithic woman from Ganj Dareh, in the Zagros Mountains of Iran, a site with early evidence for an economy based on goat herding, ca. 10,000 BP. We show that Western Iran was inhabited by a population genetically most similar to hunter-gatherers from the Caucasus, but distinct from the Neolithic Anatolian people who later brought food production into Europe. The inhabitants of Ganj Dareh made little direct genetic contribution to modern European populations, suggesting those of the Central Zagros were somewhat isolated from other populations of the Fertile Crescent. Runs of homozygosity are of a similar length to those from Neolithic farmers, and shorter than those of Caucasus and Western Hunter-Gatherers, suggesting that the inhabitants of Ganj Dareh did not undergo the large population bottleneck suffered by their northern neighbours. While some degree of cultural diffusion between Anatolia, Western Iran and other neighbouring regions is possible, the genetic dissimilarity between early Anatolian farmers and the inhabitants of Ganj Dareh supports a model in which Neolithic societies in these areas were distinct.


Subject(s)
Agriculture , DNA, Ancient/analysis , Farmers , Genetics, Population , Archaeology , DNA, Mitochondrial/genetics , Ethnicity/genetics , Europe , Female , Genetic Variation , Genome, Human , Geography , Haplotypes , Human Migration , Humans , Iran/ethnology , Phenotype , Phylogeny , Principal Component Analysis
3.
Science ; 350(6262): 820-2, 2015 Nov 13.
Article in English | MEDLINE | ID: mdl-26449472

ABSTRACT

Characterizing genetic diversity in Africa is a crucial step for most analyses reconstructing the evolutionary history of anatomically modern humans. However, historic migrations from Eurasia into Africa have affected many contemporary populations, confounding inferences. Here, we present a 12.5× coverage ancient genome of an Ethiopian male ("Mota") who lived approximately 4500 years ago. We use this genome to demonstrate that the Eurasian backflow into Africa came from a population closely related to Early Neolithic farmers, who had colonized Europe 4000 years earlier. The extent of this backflow was much greater than previously reported, reaching all the way to Central, West, and Southern Africa, affecting even populations such as Yoruba and Mbuti, previously thought to be relatively unadmixed, who harbor 6 to 7% Eurasian ancestry.


Subject(s)
Black People/genetics , Genome, Human , Human Migration , Asia , Biological Evolution , Ethiopia , Europe , Genetic Variation , Humans , Male
4.
Pharmacogenomics J ; 14(6): 503-8, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24709692

ABSTRACT

We performed whole-genome sequencing (WGS) of a case of early-stage small-cell lung cancer (SCLC) to analyze the genomic features. WGS revealed a lot of single-nucleotide variations (SNVs), small insertion/deletions and chromosomal abnormality. Chromosomes 4p, 5q, 13q, 15q, 17p and 22q contained many block deletions. Especially, copy loss was observed in tumor suppressor genes RB1 and TP53, and copy gain in oncogene hTERT. Somatic mutations were found in TP53 and CREBBP. Novel nonsynonymous (ns) SNVs in C6ORF103 and SLC5A4 genes were also found. Sanger sequencing of the SLC5A4 gene in 23 independent SCLC samples showed another nsSNV in the SLC5A4 gene, indicating that nsSNVs in the SLC5A4 gene are recurrent in SCLC. WGS of an early-stage SCLC identified novel recurrent mutations and validated known variations, including copy number variations. These findings provide insight into the genomic landscape contributing to SCLC development.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , DNA Mutational Analysis , DNA, Neoplasm/genetics , Lung Neoplasms/genetics , Sequence Analysis, DNA , Genome, Human/genetics , Genomics , Humans , Male , Middle Aged , Mutation/genetics , Polymorphism, Single Nucleotide/genetics
5.
Oncogene ; 33(46): 5341-7, 2014 Nov 13.
Article in English | MEDLINE | ID: mdl-24276243

ABSTRACT

Fusion genes act as potent oncogenes, resulting from chromosomal rearrangements or abnormal transcription in many human cancers. Although multiple gastric cancer genomes have been sequenced, the driving recurrent gene fusions have not been well characterized. Here, we used paired-end transcriptome sequencing to identify novel gene fusions in 18 human gastric cancer cell lines and 18 pairs of primary human gastric cancer tissues and their adjacent normal tissues. Multiple samples revealed expression of PPP1R1B-STARD3 fusion transcript. The presence of PPP1R1B-STARD3 correlated with elevated levels of PPP1R1B mRNA. PPP1R1B-STARD3 fusion transcript was detected in 21.3% of primary human gastric cancers but not in adjacent matched normal gastric tissues. Based on reverse transcription PCR analysis of DNA, unlike other fusions described in gastric cancer, the PPP1R1B-STARD3 appears to be generated by RNA processing without chromosomal rearrangement. Overexpression of PPP1R1B-STARD3 in MKN-28 significantly increased cell proliferation and colony formation. This increased proliferation was mediated by activation of phosphatidylinositol-3-kinase (PI3K)/AKT signaling. Furthermore, expression of PPP1R1B-STARD3 fusion transcript enhanced the tumor growth of MKN-28 cells in athymic nude mice. These findings show that PPP1R1B-STARD3 fusion transcript has a key role in subsets of gastric cancers through the activation of PI3K/AKT signaling.


Subject(s)
Carrier Proteins/genetics , Dopamine and cAMP-Regulated Phosphoprotein 32/genetics , Membrane Proteins/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Stomach Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Animals , Blotting, Western , Carcinogenesis/genetics , Carcinogenesis/metabolism , Cell Line, Tumor , Chromones/pharmacology , Enzyme Inhibitors/pharmacology , Female , Humans , Male , Mice, Nude , Middle Aged , Morpholines/pharmacology , Oncogene Proteins, Fusion/genetics , Phosphoinositide-3 Kinase Inhibitors , Phosphorylation/drug effects , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Transplantation, Heterologous , Tumor Burden/genetics
6.
Zygote ; 11(1): 69-76, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12625531

ABSTRACT

In this study, the developmental capacity and cytogenetic composition of different oocyte activation protocols was evaluated following intracytoplasmic sperm injection (ICSI) of in vitro matured bovine oocytes. Motile spermatozoa selected by Percoll density gradient were treated with 5 mM dithiothreitol (DTT) and analysed for ultrastructural changes of the head using transmission electron microscopy (TEM). The alterations in sperm morphology after DTT treatment for different times (15, 30 and 60 min) were 10%, 45-55% and 70-85%, respectively. Further, a partial decondensation of sperm heads was observed after DTT treatment for 30 min. Oocytes were injected with sperm treated with DTT for 30 min. In group 1, sperm injection was performed without any activation stimulus to the oocytes. In group 2, sham injection without sperm was performed without activating the oocytes. Oocytes injected with sperm exposed to 5 microM ionomycin for 5 min (group 3), 5 microM ionomycin + 1.9 mM dimethylaminopurine (DMAP) for 3 h (group 4) and 5 microM ionomycin + 3 h culture in M199 + 1.9 mM DMAP (group 5) were also evaluated for cleavage, development and chromosomal abnormality. Cleavage and development rates in groups 1, 2 and 3 were significantly (p < 0.05) lower than those in groups 4 and 5. The incidence of chromosomal abnormality in the embryos treated directly with DMAP after ionomycin (group 4) was higher than in group 5. We conclude that immediate DMAP treatment after ionomycin exposure of oocytes results in arrest of release of the second polar body, and thus leads to changes in chromosomal pattern. Therefore, the time interval between ionomycin and DMAP plays a crucial role in bovine ICSI.


Subject(s)
Oocytes/physiology , Sperm Injections, Intracytoplasmic/methods , Animals , Antioxidants/pharmacology , Cattle , Dithiothreitol/pharmacology , Female , Ionomycin/pharmacology , Ionophores/pharmacology , Male , Oocytes/drug effects , Pyridines/pharmacology , Time Factors
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