Jun 22, 2016

Complex Selection on Human Polyadenylation Signals Revealed by Polymorphism and Divergence Data

Genome Biology and Evolution
Yaroslav A KainovGeorgii A Bazykin

Abstract

Polyadenylation is a step of mRNA processing which is crucial for its expression and stability. The major polyadenylation signal (PAS) represents a nucleotide hexamer that adheres to the AATAAA consensus sequence. Over a half of human genes have multiple cleavage and polyadenylation sites, resulting in a great diversity of transcripts differing in function, stability, and translational activity. Here, we use available whole-genome human polymorphism data together with data on interspecies divergence to study the patterns of selection acting on PAS hexamers. Common variants of PAS hexamers are depleted of single nucleotide polymorphisms (SNPs), and SNPs within PAS hexamers have a reduced derived allele frequency (DAF) and increased conservation, indicating prevalent negative selection; at the same time, the SNPs that "improve" the PAS (i.e., those leading to higher cleavage efficiency) have increased DAF, compared to those that "impair" it. SNPs are rarer at PAS of "unique" polyadenylation sites (one site per gene); among alternative polyadenylation sites, at the distal PAS and at exonic PAS. Similar trends were observed in DAFs and divergence between species of placental mammals. Thus, selection permits PAS mutations mainly at ...Continue Reading

  • References52
  • Citations

References

  • References52
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Gene Polymorphism
Patterns
Exons
Genes
Polyadenylation Pathway
Placenta
Cytokinesis of the Fertilized Ovum
MRNA Processing
Protein Biosynthesis
Whole Genome Amplification

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Coronavirus Protein Structures

Deciphering and comparing the proteins of different coronaviruses forms a basis for understanding SARS-CoV-2 evolution and virus-receptor interactions. This feed follows studies analyzing the structures of coronavirus proteins, thereby revealing potential drug target sites.

DDX3X Syndrome

DDX3X syndrome is caused by a spontaneous mutation at conception that primarily affects girls due to its location on the X-chromosome. DDX3X syndrome has been linked to intellectual disabilities, seizures, autism, low muscle tone, brain abnormalities, and slower physical developments. Here is the latest research.

ALS: Stress Granules

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by cytoplasmic protein aggregates within motor neurons. TDP-43 is an ALS-linked protein that is known to regulate splicing and storage of specific mRNAs into stress granules, which have been implicated in formation of ALS protein aggregates. Here is the latest research.

Fusion Oncoproteins in Childhood Cancers

This feed explores the function of fusion oncoproteins in specific childhood cancers, including those from racial/ethnic minority and underserved groups, and to provide preclinical assessment of potential therapeutics and how fusion oncoproteins influence gene expression to perturb normal cellular programs to block lineage differentiation and development

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Mitotic-exit networks with cytokinesis

Cytokinesis is the highly regulated process that physically separates daughter and mother cells in late mitosis. The mitotic-exit network (MEN), the signalling pathway that drives mitotic exit, directly regulates cytokinesis. Discover the latest research on mitotic-exit networks with cytokinesis here.

DNA Replication Origin

DNA replication is initiated as specific gene sequences, called origins, that function to start DNA replication. Pre-replication complexes are assembled at these origins during the G1 phase of the cell cycle. These sequences allow for targeted activation or deactivation of replication. Discover the latest research on DNA replication origins here.