Related Experiment Video
Updated: Sep 18, 2025
11:03
Massively Parallel Reporter Assays in Cultured Mammalian Cells
Published on: August 17, 2014
21.8K
Lineage-specific regulatory evolution: insights from massively parallel reporter assays
Ryder Easterlin1, Nadav Ahituv1
1Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
Current Opinion in Genetics & Development
|June 21, 2025
Summary
Massively parallel reporter assays (MPRAs) reveal how genetic variants in regulatory elements drive evolutionary changes. This technology helps understand human evolution by studying gene expression differences across species.
Area of Science:
- Evolutionary genomics
- Regulatory element function
- Human evolution
Background:
- Lineage-specific genetic variants are crucial for evolutionary divergence.
- Cis-regulatory elements fine-tune gene expression, influencing evolutionary trajectories.
- Understanding regulatory element evolution is key to distinguishing human traits.
Purpose of the Study:
- To review the application of Massively Parallel Reporter Assays (MPRAs) in studying lineage-specific regulatory activity.
- To highlight the role of MPRAs in analyzing enhancer elements across different hominin and primate lineages.
- To discuss how MPRA technology contributes to understanding gene expression divergence.
Main Methods:
- Utilizing Massively Parallel Reporter Assays (MPRAs) to characterize genetic variants at scale.
- Analyzing regulatory activity in enhancer elements, including human accelerated regions and conserved deletions.
- Disentangling cis- and trans-regulatory contributions to gene expression using MPRA data.
Main Results:
- MPRAs have successfully identified lineage-specific regulatory activity in key evolutionary regions.
- Enhancer variations studied via MPRA affect traits distinguishing modern humans, archaic hominins, and primates.
- MPRAs effectively differentiate cis- and trans-regulatory effects on gene expression divergence.
Conclusions:
- MPRAs are a powerful tool for studying the evolution of gene regulation.
- Future integration with CRISPR and AI will further enhance our understanding of regulatory evolution.
- This approach provides critical insights into the genetic basis of human-specific traits and evolution.
Related Concept Videos
02:02Cis-regulatory Sequences
10.2K
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...
10.2K
02:05Gene Evolution - Fast or Slow?
7.5K
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
7.5K
01:23Regulation of Expression at Multiple Steps
1.0K
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.0K
02:11Reporter Genes
11.9K
Reporter genes are a type of protein-coding gene that are often tagged to a gene of interest. Once inside a target cell, reporter genes usually produce visually identifiable characteristics like fluorescence and luminescence when expressed along with the gene of interest. Thus, reporter genes “report” the presence or absence of genes of interest in an organism, determine the gene expression pattern, or track the physical location of a DNA segment or protein in the cell.
11.9K
02:24Regulation of Expression Occurs at Multiple Steps
23.5K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
23.5K
02:37Gene Duplication and Divergence
6.4K
The seminal work of Ohno in 1970 popularized the idea of gene duplication and divergence. DNA sequence comparison studies reveal that a large portion of the genes in bacteria, archaebacteria, and eukaryotes was generated by gene duplication and divergence, indicating its critical role in evolution.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...
6.4K