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Related Concept Videos

Multi-species Conserved Sequences02:51

Multi-species Conserved Sequences

Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale  studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved DNA...
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
Leaky Scanning02:28

Leaky Scanning

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 stands for...
Ribosome Profiling02:24

Ribosome Profiling

Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
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Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
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From DNA to Protein03:06

From DNA to Protein

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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Related Experiment Video

Updated: May 17, 2026

Single Cell Multiplex Reverse Transcription Polymerase Chain Reaction After Patch-clamp
10:44

Single Cell Multiplex Reverse Transcription Polymerase Chain Reaction After Patch-clamp

Published on: June 20, 2018

Selective constraint on the upstream open reading frames that overlap with coding sequences in animals.

Ming-Kung Hsu1, Feng-Chi Chen

  • 1Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.

Plos One
|November 8, 2012
PubMed
Summary
This summary is machine-generated.

Upstream open reading frames (uORFs) that overlap coding sequences (VuORFs) are slightly harmful. Optimal-context VuORFs are conserved, suggesting gained regulatory functions in smaller populations, later subject to negative selection.

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Related Experiment Videos

Last Updated: May 17, 2026

Single Cell Multiplex Reverse Transcription Polymerase Chain Reaction After Patch-clamp
10:44

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Published on: June 20, 2018

An Integrated Approach for Microprotein Identification and Sequence Analysis
09:37

An Integrated Approach for Microprotein Identification and Sequence Analysis

Published on: July 12, 2022

De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
08:23

De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data

Published on: February 18, 2022

Area of Science:

  • Genetics
  • Molecular Biology
  • Evolutionary Biology

Background:

  • Upstream open reading frames (uORFs) regulate gene expression by repressing translation of downstream coding sequences (CDS).
  • Overlapping uORFs (VuORFs) can cause translational inhibition or N-terminal peptide truncation.
  • Selective constraints on uORFs, especially VuORFs, are not well understood.

Purpose of the Study:

  • To investigate the selective constraints on VuORFs across different species.
  • To determine the impact of VuORF sequence context on their evolutionary trajectory.
  • To explore the potential for VuORFs to acquire regulatory functions.

Main Methods:

  • Comparative genomic analysis of VuORF-containing transcripts in human, mouse, and fruit fly.
  • Assessment of the proportion of genes with VuORF transcripts relative to evolutionary expectations.
  • Analysis of the relationship between VuORF context (start codon context) and selective pressure.

Main Results:

  • VuORFs are generally slightly deleterious, with fewer observed than expected across species.
  • Fruit flies exhibit a higher removal rate of VuORFs compared to mammals, correlating with effective population size.
  • Optimal-context VuAUGs are more conserved than suboptimal ones, despite being more disfavored.
  • Optimal-context VuAUGs are more conserved than expected, suggesting functional roles.

Conclusions:

  • VuORFs impose a slight deleterious effect, with removal efficiency varying by species' effective population size.
  • The conservation of optimal-context VuAUGs suggests they can be fortuitously gained and evolve regulatory functions in populations with lower selective pressures.
  • Once established, functional VuORFs become subject to negative selection, balancing their deleterious effects with their regulatory roles.