Natural selection on human microRNA binding sites inferred from SNP data
Kevin Chen1, Nikolaus Rajewsky
1Center for Comparative Functional Genomics, Department of Biology, New York University, New York, New York 10003, USA.
Nature Genetics
|October 31, 2006
Summary
Natural selection strongly impacts microRNA (miRNA) binding sites, influencing gene regulation and human fitness. These findings suggest polymorphisms in miRNA sites may cause disease.
Area of Science:
- Evolutionary biology
- Genomics
- Molecular biology
Background:
- Gene regulation is crucial for understanding evolution.
- MicroRNAs (miRNAs) are key regulators of gene expression.
- Identifying functional regulatory elements is challenging.
Purpose of the Study:
- To investigate the role of natural selection on microRNA binding sites.
- To assess the functionality of conserved and nonconserved miRNA binding sites.
- To explore the potential of miRNA binding site polymorphisms in human diseases.
Main Methods:
- Utilized SNP genotype data and population genetics.
- Analyzed conserved and nonconserved miRNA binding sites in 3' UTRs.
- Applied computational prediction models for miRNA targets.
Main Results:
- Negative selection is significantly stronger on conserved miRNA binding sites compared to other conserved motifs.
- Estimated 30%-50% of nonconserved miRNA binding sites are functional under endogenous coexpression.
- Polymorphisms in predicted miRNA binding sites are likely deleterious.
Conclusions:
- MicroRNAs contribute to Darwinian fitness.
- The study provides evidence for the functional importance of miRNA binding sites.
- MiRNA binding site polymorphisms are potential causal variants for human diseases.
Related Concept Videos
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
01:05Single Nucleotide Polymorphisms-SNPs
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...