Pervasive variation of transcription factor orthologs contributes to regulatory network evolution

PLoS Genetics
Shilpa NadimpalliMona Singh

Abstract

Differences in transcriptional regulatory networks underlie much of the phenotypic variation observed across organisms. Changes to cis-regulatory elements are widely believed to be the predominant means by which regulatory networks evolve, yet examples of regulatory network divergence due to transcription factor (TF) variation have also been observed. To systematically ascertain the extent to which TFs contribute to regulatory divergence, we analyzed the evolution of the largest class of metazoan TFs, Cys2-His2 zinc finger (C2H2-ZF) TFs, across 12 Drosophila species spanning ~45 million years of evolution. Remarkably, we uncovered that a significant fraction of all C2H2-ZF 1-to-1 orthologs in flies exhibit variations that can affect their DNA-binding specificities. In addition to loss and recruitment of C2H2-ZF domains, we found diverging DNA-contacting residues in ~44% of domains shared between D. melanogaster and the other fly species. These diverging DNA-contacting residues, found in ~70% of the D. melanogaster C2H2-ZF genes in our analysis and corresponding to ~26% of all annotated D. melanogaster TFs, show evidence of functional constraint: they tend to be conserved across phylogenetic clades and evolve slower than other d...Continue Reading

References

Apr 11, 1975·Science·M C King, A C Wilson
Jun 20, 1991·Nature·J H McDonald, M Kreitman
Jul 25, 1969·Science·R J Britten, E H Davidson
Jul 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·H R Pelham, D D Brown
Nov 21, 1997·Computer Applications in the Biosciences : CABIOS·Z Yang
Aug 15, 2000·Annual Review of Biophysics and Biomolecular Structure·S A WolfeC O Pabo
Aug 31, 2000·Journal of Molecular Biology·C NotredameJ Heringa
Sep 27, 2000·Evolution; International Journal of Organic Evolution·D L Stern
May 22, 2001·Cellular and Molecular Life Sciences : CMLS·S Iuchi
Jun 8, 2001·Annual Review of Biochemistry·C O PaboR A Grant
Feb 23, 2002·Nature·Matthew RonshaugenWilliam McGinnis
Apr 5, 2002·Genome Research·W James Kent
Jun 26, 2002·Molecular Biology and Evolution·Emmanouil T Dermitzakis, Andrew G Clark
Jul 5, 2002·Genome Research·Olivier LespinetL Aravind
Nov 7, 2002·Journal of Molecular Biology·Panayiotis V BenosGary D Stormo
Jan 10, 2003·Nucleic Acids Research·V MatysE Wingender
Jun 5, 2003·Molecular Biology and Evolution·Gregory A WrayLaura A Romano
Oct 2, 2003·Genome Biology·Raul Urrutia
Oct 18, 2003·Gene·Françoise MazetSebastian M Shimeld
Mar 11, 2004·Journal of Molecular Evolution·Stanley A SawyerDaniel L Hartl
Jun 3, 2004·Genome Research·Gavin E CrooksSteven E Brenner
Dec 1, 2004·Annual Review of Genetics·John S Taylor, Jeroen Raes
Jul 8, 2005·PLoS Biology·Sean B Carroll
Aug 17, 2005·PLoS Computational Biology·Tommy KaplanHanah Margalit
Oct 17, 2006·PLoS Computational Biology·Alan M MosesMichael B Eisen
Feb 17, 2007·Nature Reviews. Genetics·Gregory A Wray
May 12, 2007·Evolution; International Journal of Organic Evolution·Hopi E Hoekstra, Jerry A Coyne
May 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Benjamin Prud'hommeSean B Carroll
May 29, 2007·PLoS Computational Biology·Scott W Doniger, Justin C Fay
Jun 16, 2007·Molecular Biology and Evolution·Ho-Ryun ChungHerbert Jäckle
Aug 11, 2007·Science·Anthony R BornemanMichael Snyder

❮ Previous
Next ❯

Citations

Mar 3, 2019·Molecular Biology and Evolution·Otmane LamrabetThomas Hindré
May 28, 2019·Nature Genetics·Samuel A LambertTimothy R Hughes
Jul 14, 2020·Bioinformatics·Moses StamboulianPredrag Radivojac
Aug 10, 2017·Nature Communications·Tamar FriedlanderGašper Tkačik

❮ Previous
Next ❯

Methods Mentioned

BETA
ChIP
gene knockout
gene knockouts

Software Mentioned

Notung
modENCODE
Pfam
fimo
WebLogo
BLAT
hmmsearch
Coffee
GO Term Finder
FlyAtlas

Related Concepts

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.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

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.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.