Gene and Genome

Gene and Genome

Denovo gene evolution refers to genes arising from:

De novo gene birth describes emergence of novel protein-coding genes from previously non-coding DNA rather than duplication or horizontal acquisition. Intergenic regions, antisense transcripts or intronic sequences acquire mutations creating open reading frame, transcription factor binding sites and translation signals. Phylostratigraphy reveals young lineage-specific genes initially disordered, moderately expressed, evolving under purifying selection after gaining function. Examples in yeast, Drosophila and mammals involve emergence from non-coding RNA that becomes stably translated. This mechanism expands proteome innovatively beyond modifications of ancestral genes.

Ref: McLysaght A, Guerzoni D, PNAS 2015: De Novo Gene Evolution Refers to Genes Arising from Non-coding DNA

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Gene and Genome

Most dsDNA viruses have genome organization that is:

Double-stranded DNA viruses generally package genome as single continuous molecule containing all essential genes on one chromosome, termed monopartite organization. Herpesviruses, poxviruses, adenoviruses and most bacteriophages encode replication, transcription and structural proteins contiguously, ensuring complete genetic information delivered per particle. Segmented dsDNA viruses are exceptionally rare; multipartite organization characteristic of some plant RNA viruses requires multiple particles for infection. Monopartite architecture simplifies replication via theta or strand displacement, allows tight regulation of temporal gene classes and avoids reassortment necessitated by segmentation.

Ref: Fields et al., Virology: Most dsDNA Viruses Have Genome Organization That is Monopartite

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Gene and Genome

Ambisense genome contains:

Ambisense coding strategy observed in arenaviruses, phleboviruses and tospoviruses combines positive and negative polarity within same RNA segment. Each segment contains two open reading frames in opposite orientation separated by intergenic hairpin acting as transcription termination signal. One gene is expressed from genomic strand as negative-sense, the second from antigenomic complementary strand as positive-sense after replication. This arrangement allows regulation of gene expression timing and genome compactness. It differs from fully negative or positive genomes by encoding proteins from both strands of single molecule.

Ref: Nguyen M, Haenni AL, Virology 2003: Ambisense Genome Contains Both Sense in Same RNA

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Gene and Genome

Segmented genome is typical of:

Segmented genomes divide viral nucleic acid into multiple fragments packaged within single particle or distinct particles requiring co-infection for productive replication. Orthomyxoviridae including influenza A virus carry eight negative-sense RNA segments encoding polymerase subunits, hemagglutinin, neuraminidase, nucleoprotein and nonstructural proteins, facilitating genetic reassortment during co-infection leading to antigenic shift responsible for pandemics. Reoviruses have 10-12 dsRNA segments, bunyaviruses three segments. Segmentation contrasts monopartite genomes like poliovirus containing single continuous molecule. Electrophoresis of purified RNA reveals multiple bands diagnostic of segmentation and reassortment potential.

Ref: Palese P, Shaw ML, Orthomyxoviridae, Fields Virology: Segmented Genome Typical of Influenza Virus

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Gene and Genome

HIV genome is:

Human immunodeficiency virus type 1 possesses lentiviral genome unique among retroviruses for efficient targeting of non-dividing cells. Encapsidated within conical capsid are two identical, non-covalently linked copies of ~9.2 kb positive-sense RNA capped and polyadenylated, bonded at dimer linkage structure near 5' end. Diploidy facilitates recombination and complementation of defects. Each RNA associates with nucleocapsid protein, reverse transcriptase and integrase. After entry, reverse transcriptase copies one RNA into double-stranded proviral DNA integrated into host chromosome by integrase, establishing persistent infection hallmarked by high mutation rate.

Ref: Freed EO, Virology 2015: HIV Genome is Two Identical RNA Copies, Lentiviral Diploid Genome

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Gene and Genome

Retroviruses contain genome which is:

Retroviruses such as HIV, MLV and HTLV store genetic information as two copies of positive-sense single-stranded RNA genome of 7-12 kb containing gag, pol and env genes flanked by long terminal repeats. Positive-sense denotes same polarity as mRNA, translatable although retroviruses first reverse transcribe RNA into double-stranded DNA provirus using virion reverse transcriptase. Diploid RNA allows recombination during reverse transcription, enhancing diversity. Packaging two RNAs ensures repair of breaks and promotes strand switching. Genome organization distinguishes them from negative- and double-stranded RNA viruses.

Ref: Coffin JM, Hughes SH, Varmus HE, Retroviruses, Cold Spring Harbor Press: Retrovirus Genome is ssRNA Positive Sense

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Gene and Genome

Negative‑sense RNA viruses require which enzyme first?

Negative-sense RNA viruses carry genome complementary to mRNA, unable to be translated directly by host ribosomes. Influenza, rabies, Ebola and measles viruses package RNA-dependent RNA polymerase within virion to transcribe genome into positive-sense cRNAs and mRNAs immediately after entry. This polymerase synthesizes complementary strand serving as template for replication and as translatable message bearing 5' cap obtained via cap-snatching. Host RNA polymerase II cannot transcribe RNA genomes, precluding reliance on cellular enzyme. Requirement for preformed viral polymerase explains why purified genomic RNA alone is non-infectious.

Ref: Baltimore D., PNAS 1971: Negative-Sense RNA Viruses Require RNA-Dependent RNA Polymerase First

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Gene and Genome

Viroids replicate via:

Viroids replicate autonomously using host transcriptional machinery despite lack of protein-coding capacity. Most pospiviroids utilize asymmetric rolling circle mechanism where circular RNA is transcribed by host RNA polymerase II into concatemeric complementary strands cleaved by host RNase and ligated to generate new circles. Chloroplast-replicating avsunviroids use symmetric pathway with self-cleavage via hammerhead ribozyme motifs. No DNA intermediate is involved, distinguishing them from retroviruses. Efficiency depends on RNA structure acting as promoter for Pol II, diverting enzyme from DNA templates to RNA-directed transcription.

Ref: Flores et al., Annu Rev Phytopathology 2005: Viroids Replicate via Rolling Circle Mechanism

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Gene and Genome

Viroids are characterized by:

Viroids represent subviral pathogens composed solely of small, non-coding, single-stranded circular RNA without encapsidation or protein synthesis capability. Ranging from 246 to 401 nucleotides, they form highly base-paired rod-like secondary structure conferring resistance to nucleases that hijack host RNA polymerase II for replication via rolling circle mechanism. Infecting higher plants causing diseases like potato spindle tuber, they replicate in nucleus or chloroplast. Absence of capsid distinguishes them from viruses. Small size, circularity and lack of protein coat are diagnostic features separating viroids from virusoids and satellites.

Ref: Diener TO, Annu Rev Virology: Viroids Characterized by ss Circular RNA Without Protein Coat

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Gene and Genome

Which complex is encoded by ND genes in mitochondria?

Mitochondrial DNA encodes 13 hydrophobic core subunits essential for electron transport chain, distributed across complexes. NADH dehydrogenase genes ND1, ND2, ND3, ND4, ND4L, ND5 and ND6 encode subunits of complex I, NADH:ubiquinone oxidoreductase, largest respiratory complex initiating electron transfer from NADH to ubiquinone and pumping protons. Remaining genes include cytochrome b for complex III, COX1-3 for complex IV and ATP6, ATP8 for complex V. Complex II is entirely nuclear encoded. Mutations in ND genes cause Leber hereditary optic neuropathy and mitochondrial encephalomyopathies.

Ref: DiMauro S, Schon EA, Mitochondrial Respiratory-Chain Diseases, NEJM 2003: ND Genes Encode Complex I

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Gene and Genome

Human mitochondrial genome encodes:

Human mitochondrial DNA is a circular, 16.6 kb molecule inherited maternally, lacking introns and histones, encoding components of oxidative phosphorylation system. Initial complete sequencing by Anderson et al. revealed 37 genes: 13 protein coding for subunits of respiratory complexes I, III, IV and V, 22 transfer RNAs and 2 ribosomal RNAs 12S and 16S. Non-coding D-loop regulates replication and transcription. Compact organization with overlapping genes and minimal intergenic spacers maximizes coding capacity. Counting only protein genes yields 13, but total gene number including RNAs is 37.

Ref: Anderson et al., Nature 1981: Human Mitochondrial Genome Encodes 37 Genes, mtDNA Sequencing

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Gene and Genome

Plasmids are:

Plasmids are accessory genetic elements replicating independently of main chromosome through own origin of replication compatible with host initiation factors. Typically circular double-stranded DNA of few kilobases to over 100 kb, encoding antibiotic resistance, virulence, catabolic pathways or conjugation machinery, they are dispensable under non-selective conditions and may be lost without lethal effect. Found predominantly in bacteria, also in some archaea and eukaryotes. Classification by incompatibility groups and mobilization ability underlies biotechnology vectors derived from natural plasmids like pSC101 and pUC for cloning and expression.

Ref: Novick RP, Annu Rev Microbiology 1987: Plasmids are Extra-Chromosomal DNA, Bacterial Plasmids

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