The MOXD2 gene encodes a membrane-bound monooxygenase similar to dopamine-β-hydroxylase, and has been proposed to be associated with olfaction. In this study, we analyzed MOXD2 genes from 64 mammalian species, and identified loss-of-function mutations in apes (humans, Sumatran and Bornean orangutans, and five gibbon species from the four major gibbon genera), toothed whales (killer whales, bottlenose dolphins, finless porpoises, baijis, and sperm whales), and baleen whales (minke whales and fin whales). We also identified a shared 13-nt deletion in the last exon of Old World cercopithecine monkeys that results in conversion of a membrane-bound protein to a soluble form. We hypothesize that the frequent inactivation and alteration of MOXD2 genes in catarrhines and whales may be associated with the evolution of olfaction in these clades.
Humans have acquired many distinct evolutionary traits after the human-chimpanzee divergence. These phenotypes have resulted from genetic changes that occurred in the human genome and were retained by natural selection. Comparative primate genome analyses reveal that loss-of-function mutations are common in the human genome. Some of these gene inactivation events were revealed to be associated with the emergence of advantageous phenotypes and were therefore positively selected and fixed in modern humans (the “less-ismore” hypothesis). Representative cases of human gene inactivation and their functional implications are presented in this review. Functional studies of additional inactive genes will provide insight into the molecular mechanisms underlying acquisition of various human-specific traits. [BMB Reports 2015; 48(7): 373-379]
Heterologous protein production in Saccharomyces cerevisiae is a useful and effective strategy with many advantages, including the secretion of proteins that require posttranslational processing. However, heterologous proteins in S. cerevisiae are often secreted at comparatively low levels. To improve the production of the heterologous protein, human granulocyte colony‐stimulating factor (hG‐CSF) in S. cerevisiae , a secretion‐enhancing peptide cassette including an hIL‐1β‐derived propeptide, was added and used as a secretion enhancer to alleviate specific bottlenecks in the yeast secretory pathway. The effects of three key parameters— N ‐glycosylation, net negative charge balance, and glycine‐rich flexible linker—were investigated in batch cultures of S. cerevisiae . Using a three‐stage design involving screening, selection, and optimization, the production and secretion of hG‐CSF by S. cerevisiae were significantly increased. The amount of extracellular mature hG‐CSF produced by the optimized propeptide after the final stage increased by 190% compared to that of the original propeptide. Although hG‐CSF was used as the model protein in the current study, this strategy applies to the enhanced production of other heterologous proteins, using S. cerevisiae as the host.
Heat shock RNA 1 (HSR1) is described as a "eukaryotic heat-sensing noncoding RNA" that regulates heat shock response in human and other eukaryotic cells. Highly conserved HSR1 sequences have been identified from humans, hamsters, Drosophila, Caenorhabditis elegans, and Arabidopsis. In a previous study, however, it was suggested that HSR1 had originated from a bacterial genome. HSR1 showed no detectible nucleotide sequence similarity to any eukaryotic sequences but harbored a protein coding region that showed amino-acid sequence similarity to bacterial voltage-gated chloride channel proteins. The bacterial origin of HSR1 was not convincible because the nucleotide sequence similarity was marginal. In this study, we have found that a genomic contig sequence of Comamonas testosteroni strain JL14 contained a sequence virtually identical to that of HSR1, decisively confirming the bacterial origin of HSR1. Thus, HSR1 is an exogenous RNA, which can ectopically trigger heat shock response in eukaryotes. Therefore, it is no longer appropriate to cite HSR1 as a "eukaryotic functional noncoding RNA."
Plant pathogenic RNA viruses are present in a variety of plant-based foods. When ingested by humans, these viruses can survive the passage through the digestive tract, and are frequently detected in human feces. Kimchi is a traditional fermented Korean food made from cabbage or vegetables, with a variety of other plant-based ingredients, including ground red pepper and garlic paste. We analyzed microbial metatranscriptome data from kimchi at five fermentation stages to identify plant RNA virus-derived sequences. We successfully identified a substantial amount of plant RNA virus sequences, especially during the early stages of fermentation: 23.47% and 16.45% of total clean reads on days 7 and 13, respectively. The most abundant plant RNA virus sequences were from pepper mild mottle virus, a major pathogen of red peppers; this constituted 95% of the total RNA virus sequences identified throughout the fermentation period. We observed distinct sequencing read-depth distributions for plant RNA virus genomes, possibly implying intrinsic and/or technical biases during the metatranscriptome generation procedure. We also identified RNA virus sequences in publicly available microbial metatranscriptome data sets. We propose that metatranscriptome data may serve as a valuable resource for RNA virus detection, and a systematic screening of the ingredients may help prevent the use of virus-infected low-quality materials for food production.
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