Evidence map›Paper›PMID 27324920›Full record

ArticleGenome biology and evolution2016

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

Yaroslav A Kainov, Vasily N Aushev, Sergey A Naumenko, Elena M Tchevkina, Georgii A Bazykin

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Article in Genome biology and evolution, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

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0cells of the map it votes in
6citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Yaroslav A KainovCentre 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.
Vasily N AushevOncogenes Regulation Department, N.N. Blokhin Russian Cancer Research Center, Institute of Carcinogenesis, Moscow, Russia Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York.
Sergey A NaumenkoInstitute for Information Transmission Problems (Kharkevich Institute) of the Russian Academy of Sciences, Moscow, Russia Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Canada.
Elena M TchevkinaOncogenes Regulation Department, N.N. Blokhin Russian Cancer Research Center, Institute of Carcinogenesis, Moscow, Russia.
Georgii A BazykinInstitute for Information Transmission Problems (Kharkevich Institute) of the Russian Academy of Sciences, Moscow, Russia Skolkovo Institute of Science and Technology, Skolkovo, Russia Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Russia Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Russia Pirogov Russian National Research Medical University, Moscow, Russia yaroslav.kainov@kcl.ac.uk gbazykin@iitp.ru.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 redundant and/or weakly functional PAS. Nevertheless, a fraction of the SNPs at PAS hexamers likely affect gene functions; in particular, some of the observed SNPs are associated with disease.

Indexed as

Genome, HumanExonsGene FrequencyHumansPolyadenylationPolymorphism, Single NucleotideRNA 3' Polyadenylation SignalsRNA, MessengerRNA, Messenger1000 genomesAATAAAmRNA processingpolyadenylationSNP

Identifiers

PMID27324920
PMCPMC4943204

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