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Related Concept Videos

Leaky Scanning02:28

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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
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While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.
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Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
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The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
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Novel Sequence Discovery by Subtractive Genomics
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Novel start codons introduce novel coding sequences in the human genomes.

He Zhang1, Yang Xie2

  • 1Quantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. he.zhang@utsouthwestern.edu.

Scientific Reports
|May 19, 2023
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Summary
This summary is machine-generated.

Start-gain mutations create new gene start codons, enhancing translation initiation. Researchers identified 829 polymorphic and 26 human-specific start codons with significant functional impacts.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Human Genetics

Background:

  • Start-gain mutations introduce novel start codons, potentially altering gene function and coding sequences.
  • These mutations can lead to new protein isoforms or affect gene expression regulation.

Purpose of the Study:

  • To systematically investigate novel start codons (polymorphic and fixed) in the human genome.
  • To analyze the functional impact and evolutionary significance of these start-gain mutations.

Main Methods:

  • Identification and characterization of start-gain single nucleotide variants (SNVs) in human populations.
  • Comparative genomic analysis to identify human-specific fixed start codons.
  • Assessment of translation initiation activity for novel start codons.

Main Results:

  • Identified 829 polymorphic start-gain SNVs with significantly higher translation initiation activity.
  • Discovered 26 human-specific start codons fixed after human-chimpanzee divergence, exhibiting high initiation activity.
  • Detected negative selection signals in novel coding sequences arising from human-specific start codons.

Conclusions:

  • Novel start codons generated by start-gain mutations can significantly enhance translation initiation.
  • Human-specific start codons represent important evolutionary events with functional consequences.
  • These findings highlight the role of start-gain mutations in human genome evolution and potential disease associations.