The intronic branch point sequence is under strong evolutionary constraint in the bovine and human genome
| Autor: | Xena M. Mapel, Hubert Pausch, Naveen Kumar Kadri |
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| Rok vydání: | 2021 |
| Předmět: |
Male
QH301-705.5 Medicine (miscellaneous) Single-nucleotide polymorphism Computational biology Biology Genome General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Negative selection 0302 clinical medicine Genetics Animals Humans Biology (General) 030304 developmental biology 2. Zero hunger 0303 health sciences Genome Human Alternative splicing Intron Exons Genomics Biological Evolution Introns Bovine genome RNA splicing Mutation Human genome Cattle General Agricultural and Biological Sciences 030217 neurology & neurosurgery |
| Zdroj: | Communications Biology Communications Biology, 4 Communications Biology, Vol 4, Iss 1, Pp 1-13 (2021) |
| ISSN: | 2399-3642 |
| Popis: | The branch point sequence is a cis-acting intronic motif required for mRNA splicing. Despite their functional importance, branch point sequences are not routinely annotated. Here we predict branch point sequences in 179,476 bovine introns and investigate their variability using a catalogue of 29.4 million variants detected in 266 cattle genomes. We localize the bovine branch point within a degenerate heptamer “nnyTrAy”. An adenine residue at position 6, that acts as branch point, and a thymine residue at position 4 of the heptamer are more strongly depleted for mutations than coding sequences suggesting extreme purifying selection. We provide evidence that mutations affecting these evolutionarily constrained residues lead to alternative splicing. We confirm evolutionary constraints on branch point sequences using a catalogue of 115 million SNPs established from 3,942 human genomes of the gnomAD database. Kadri and colleagues present the evolutionary constraints of the branch point motifs in the bovine and human genome. The functional role of these predicted branch points sequences in the bovine genome is inferred using splicing quantitative trait loci analyses. |
| Databáze: | OpenAIRE |
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