Related Experiment Video
Updated: Mar 19, 2026
08:35
Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
Published on: June 24, 2021
6.5K
Complex Selection on Human Polyadenylation Signals Revealed by Polymorphism and Divergence Data.
Yaroslav A Kainov1, Vasily N Aushev2, Sergey A Naumenko3
1Centre for Developmental Neurobiology, King's College London, London, United Kingdom Oncogenes Regulation Department, N.N. Blokhin Russian Cancer Research Center, Institute of Carcinogenesis, Moscow, Russia yaroslav.kainov@kcl.ac.uk gbazykin@iitp.ru.
Genome Biology and Evolution
|June 22, 2016
Summary
Selection pressures shape polyadenylation signals (PAS) in human genes. Mutations improving PAS efficiency are favored, while those impairing it are selected against, especially at crucial polyadenylation sites.
Area of Science:
- Genetics
- Molecular Biology
- Evolutionary Biology
Background:
- Polyadenylation is a critical mRNA processing step influencing gene expression and stability.
- The major polyadenylation signal (PAS) is a conserved hexamer (AATAAA consensus).
- Alternative polyadenylation (APA) generates transcript diversity, impacting function and stability.
Purpose of the Study:
- Investigate evolutionary selection patterns on Polyadenylation Signal (PAS) hexamers.
- Analyze the impact of single nucleotide polymorphisms (SNPs) on PAS function and conservation.
- Determine how selection acts on PAS variants across different types of polyadenylation sites.
Main Methods:
- Utilized whole-genome human polymorphism data.
- Analyzed interspecies divergence data in placental mammals.
- Compared derived allele frequencies (DAFs) and conservation of PAS hexamer SNPs.
Main Results:
- PAS hexamers show depletion of SNPs, indicating negative selection.
- SNPs improving PAS cleavage efficiency exhibit increased DAF compared to those impairing it.
- SNPs are rarer at unique, distal, and exonic polyadenylation sites.
Conclusions:
- Selection permits PAS mutations primarily at redundant or weakly functional sites.
- A subset of PAS SNPs may impact gene function and are associated with diseases.
- Understanding PAS evolution provides insights into gene regulation and disease mechanisms.
Related Concept Videos
02:51Multi-species Conserved Sequences
4.9K
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...
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
4.9K
00:43Bacterial RNA Polymerase
33.5K
Unlike eukaryotes, bacteria use a single RNA Polymerase (RNAP) to transcribe all genes. The different subunits of bacterial RNAPhave distinct functions. The multisubunit structure of the bacterial RNAP helps the enzyme to maintain catalytic function, facilitate assembly, interact with DNA and RNA, and self-regulate its activity.
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
33.5K
01:05Single Nucleotide Polymorphisms-SNPs
19.6K
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,...
19.6K
02:37Gene Duplication and Divergence
8.2K
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...
8.2K
02:23RNA Editing
10.1K
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
10.1K
02:28Leaky Scanning
5.8K
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...
5.8K