Ribosomal DNA copy number is coupled with gene expression variation and mitochondrial abundance in humans.

Abstract:

:Ribosomes are essential intracellular machines composed of proteins and RNA molecules. The DNA sequences (rDNA) encoding ribosomal RNAs (rRNAs) are tandemly repeated and give origin to the nucleolus. Here we develop a computational method for estimating rDNA dosage (copy number) and mitochondrial DNA abundance using whole-genome short-read DNA sequencing. We estimate these attributes across hundreds of human genomes and their association with global gene expression. The analyses uncover abundant variation in rDNA dosage that is coupled with the expression of hundreds of functionally coherent gene sets. These include associations with genes coding for chromatin components that target the nucleolus, including CTCF and HP1β. Finally, the data show an inverse association between rDNA dosage and mitochondrial DNA abundance that is manifested across genotypes. Our findings uncover a novel and cryptic source of hypervariable genomic diversity with global regulatory consequences (ribosomal eQTL) in humans. The variation provides a mechanism for cellular homeostasis and for rapid and reversible adaptation.

journal_name

Nat Commun

journal_title

Nature communications

authors

Gibbons JG,Branco AT,Yu S,Lemos B

doi

10.1038/ncomms5850

subject

Has Abstract

pub_date

2014-09-11 00:00:00

pages

4850

issn

2041-1723

pii

ncomms5850

journal_volume

5

pub_type

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