TY - JOUR
T1 - The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome
AU - FANTOM consortium
AU - Hurst, Laurence D.
AU - Ghanbarian, Avazeh T.
AU - Forrest, Alistair R.R.
AU - Huminiecki, Lukasz
AU - Rehli, Michael
AU - Kenneth Baillie, J.
AU - de Hoon, Michiel J.L.
AU - Haberle, Vanja
AU - Lassmann, Timo
AU - Kulakovskiy, Ivan V.
AU - Lizio, Marina
AU - Itoh, Masayoshi
AU - Andersson, Robin
AU - Mungall, Christopher J.
AU - Meehan, Terrence F.
AU - Schmeier, Sebastian
AU - Bertin, Nicolas
AU - Jørgensen, Mette
AU - Dimont, Emmanuel
AU - Arner, Erik
AU - Schmidl, Christian
AU - Schaefer, Ulf
AU - Medvedeva, Yulia A.
AU - Plessy, Charles
AU - Vitezic, Morana
AU - Severin, Jessica
AU - Semple, Colin A.
AU - Ishizu, Yuri
AU - Young, Robert S.
AU - Francescatto, Margherita
AU - Alam, Intikhab
AU - Albanese, Davide
AU - Altschuler, Gabriel M.
AU - Arakawa, Takahiro
AU - Archer, John A.C.
AU - Arner, Peter
AU - Babina, Magda
AU - Baker, Sarah
AU - Balwierz, Piotr J.
AU - Beckhouse, Anthony G.
AU - Pradhan, Swati Bhatt
AU - Blake, Judith A.
AU - Blumenthal, Antje
AU - Bodega, Beatrice
AU - Bonetti, Alessandro
AU - Briggs, James
AU - Brombacher, Frank
AU - Maxwell Burroughs, A.
AU - Califano, Andrea
AU - Yamaguchi, Yoko
N1 - Publisher Copyright:
© 2015 Hurst et al.
PY - 2015/12/18
Y1 - 2015/12/18
N2 - X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X’s gene content, gene expression, and evolution.
AB - X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X’s gene content, gene expression, and evolution.
UR - http://www.scopus.com/inward/record.url?scp=84969295765&partnerID=8YFLogxK
U2 - 10.1371/journal.pbio.1002315
DO - 10.1371/journal.pbio.1002315
M3 - Article
C2 - 26685068
AN - SCOPUS:84969295765
SN - 1544-9173
VL - 13
JO - PLoS Biology
JF - PLoS Biology
IS - 12
M1 - e1002315
ER -