Evolutionary Origins of Pax6 Control of Crystallin Genes

Cvekl, Aleš; Zhao, Yilin; McGreal, Rebecca; Xie, Qing; Gu, Xun; Zheng, Deyou

doi:10.1093/gbe/evx153

Cited by 24 publications

(20 citation statements)

References 128 publications

(192 reference statements)

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“…For example, sequence comparisons have detailed the recruitment of crystallins during the initial evolution of the vertebrate lens, finding that the α-crystallins are related to extra-lenticular small heat shock proteins ( Wistow & Piatigorsky, 1988 ). A subsequent gene duplication event was followed by divergence in transcriptional regulation and expression between the two resulting paralogs (αA and αB-crystallin) ( Cvekl et al, 2017 ). A more recent evolutionary change in the regulation of α-crystallins was investigated in the blind mole rat, in which the αB-crystallin promoter has specifically lost lens activity, presumably reflecting the degenerated eyes of this subterranean species ( Hough et al, 2002 ).…”

Section: Introductionmentioning

confidence: 99%

The zebrafish as a model system for analyzing mammalian and native α-crystallin promoter function

Posner

Murray

McDonald

et al. 2017

PeerJ

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Previous studies have used the zebrafish to investigate the biology of lens crystallin proteins and their roles in development and disease. However, little is known about zebrafish α-crystallin promoter function, how it compares to that of mammals, or whether mammalian α-crystallin promoter activity can be assessed using zebrafish embryos. We injected a variety of α-crystallin promoter fragments from each species combined with the coding sequence for green fluorescent protein (GFP) into zebrafish zygotes to determine the resulting spatiotemporal expression patterns in the developing embryo. We also measured mRNA levels and protein abundance for all three zebrafish α-crystallins. Our data showed that mouse and zebrafish αA-crystallin promoters generated similar GFP expression in the lens, but with earlier onset when using mouse promoters. Expression was also found in notochord and skeletal muscle in a smaller percentage of embryos. Mouse αB-crystallin promoter fragments drove GFP expression primarily in zebrafish skeletal muscle, with less common expression in notochord, lens, heart and in extraocular regions of the eye. A short fragment containing only a lens-specific enhancer region increased lens and notochord GFP expression while decreasing muscle expression, suggesting that the influence of mouse promoter control regions carries over into zebrafish embryos. The two paralogous zebrafish αB-crystallin promoters produced subtly different expression profiles, with the aBa promoter driving expression equally in notochord and skeletal muscle while the αBb promoter resulted primarily in skeletal muscle expression. Messenger RNA for zebrafish αA increased between 1 and 2 days post fertilization (dpf), αBa increased between 4 and 5 dpf, but αBb remained at baseline levels through 5 dpf. Parallel reaction monitoring (PRM) mass spectrometry was used to detect αA, aBa, and αBb peptides in digests of zebrafish embryos. In whole embryos, αA-crystallin was first detected by 2 dpf, peaked in abundance by 4–5 dpf, and was localized to the eye. αBa was detected in whole embryo at nearly constant levels from 1–6 dpf, was also localized primarily to the eye, and its abundance in extraocular tissues decreased from 4–7 dpf. In contrast, due to its low abundance, no αBb protein could be detected in whole embryo, or dissected eye and extraocular tissues. Our results show that mammalian α-crystallin promoters can be efficiently screened in zebrafish embryos and that their controlling regions are well conserved. An ontogenetic shift in zebrafish aBa-crystallin promoter activity provides an interesting system for examining the evolution and control of tissue specificity. Future studies that combine these promoter based approaches with the expanding ability to engineer the zebrafish genome via techniques such as CRISPR/Cas9 will allow the manipulation of protein expression to test hypotheses about lens crystallin function and its relation to lens biology and disease.

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Section: Introductionmentioning

confidence: 99%

The zebrafish as a model system for analyzing mammalian and native α-crystallin promoter function

Posner

Murray

McDonald

et al. 2017

PeerJ

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“…Characterization of the CgPMU3 promoter UAS has uncovered a potential new mechanism to regulate thiamine starvation genes and has demonstrated an interesting aspect of cis regulatory acquisition. Often, there is the recruitment of the same transcription factors, and thus, the apparent convergent evolution of the same cis sequences to bind those factors (Dalal et al 2016;Cvekl et al 2017;Kuang et al 2018). However, we observe a novel cis regulatory sequence in a promoter that is recently evolved in a different genetic milieu (i.e., lack of THI2), but still gives the same output as many other THI genes.…”

Section: Discussionmentioning

confidence: 73%

A NovelcisElement Achieves the Same Solution as an AncestralcisElement During Thiamine Starvation inCandida glabrata

Iosue

Gulotta

Selhorst

et al. 2020

G3 Genes|Genomes|Genetics

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Regulatory networks often converge on very similar cis sequences to drive transcriptional programs due to constraints on what transcription factors are present. To determine the role of constraint loss on cis element evolution, we examined the recent appearance of a thiamine starvation regulated promoter in Candida glabrata. This species lacks the ancestral transcription factor Thi2, but still has the transcription factor Pdc2, which regulates thiamine starvation genes, allowing us to determine the effect of constraint change on a new promoter. We identified two different cis elements in C. glabrata - one present in the evolutionarily recent gene called CgPMU3, and the other element present in the other thiamine (THI) regulated genes. Reciprocal swaps of the cis elements and incorporation of the S. cerevisiaeThi2 transcription factor-binding site into these promoters demonstrate that the two elements are functionally different from one another. Thus, this loss of an imposed constraint on promoter function has generated a novel cis sequence, suggesting that loss of trans constraints can generate a non-convergent pathway with the same output.

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“…The binding sites for PAX6 as a transcription factor occupy an incredible position of similarity to sites used to regulate a number of stress response networks. Heat shock elements (found in lenses), antioxidant response elements (found throughout the eye), and p53 binding sites (cell cycle arrest and pigment expression) are all exceedingly similar to the 'optimal' PAX6 binding site (Cvekl et al 2017) . Very few mutations are needed to change any one of these promoter regions into one that would recognize PAX6 as an activator.…”

Section: Genomic Regulation Transforms Stress Response Network Inmentioning

confidence: 99%

“…By examining literature surrounding a vertebrate copy of PAX, PAX6, we once again see links to ROS and UV stress responses that may have driven the disambugation of light-mediated stress responses from the stimulus of UV exposure (Mikkola et al 1999;Ou et al 2008;Laggner et al 2017) . The sequence similarity between PAX6 promoters and the promoters driving crucial portions of the UV-response network facilitated PAX6 to become adopted as an 'unified' activator (Cvekl et al 2017) . With UV light still sufficient, but no longer necessary, developmental processes could express the response pathways above in cohesive, photosensitive 'eyespots' permanently presensitized to track levels of UV light from a distance, setting in motion the evolution of more complex eyes.…”

Section: Genomic Regulation Transforms Stress Response Network Inmentioning

confidence: 99%

Light-Induced Stress as a Primary Evolutionary Driver of Eye Origins

Swafford

Oakley

2019

Preprint

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Eyes are quintessential complex traits and our understanding of their evolution guides understanding of trait evolution in general. A long-standing account of eye evolution argues natural selection favors morphological variations that allow increased functionality for sensing light (Darwin 1859; v. Salvini-Plawen and Mayr 1977; Nilsson and Pelger 1994; Nilsson 2013). While certainly true in part, this focus on visual performance does not entirely explain why diffuse photosensitivity persists even after eyes evolve, or why eyes evolved many times, each time using similar building blocks. Here we briefly review a vast literature indicating most genetic components of eyes historically responded to stress caused directly by light, including UV damage of DNA, oxidative stress, and production of aldehydes. We propose light-induced stress had a direct and prominent role in the evolution of eyes by bringing together genes to repair and prevent damage from light-stress, both before and during the evolution of eyes themselves. Stress-repair and stress-prevention genes were perhaps originally deployed as plastic responses to light and/or as beneficial mutations genetically driving expression where light was prominent. These stress-response genes sense, shield, and refract light but only under UV exposure. Once under regulatory-genetic control, they could be expressed before UV stress appeared, evolve as a single unit, and be influenced by natural selection to increase functionality for sensing light, ultimately leading to complex eyes and behaviors. Recognizing the potentially prominent role of stress in eye evolution invites discussions of plasticity and assimilation and provides a hypothesis for why similar genes are repeatedly used in convergent eyes. Broadening the drivers of eye evolution encourages consideration of multi-faceted mechanisms of plasticity/assimilation and mutation/selection for complex novelties and innovations in general.

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Evolutionary Origins of Pax6 Control of Crystallin Genes

Cited by 24 publications

References 128 publications

The zebrafish as a model system for analyzing mammalian and native α-crystallin promoter function

The zebrafish as a model system for analyzing mammalian and native α-crystallin promoter function

A NovelcisElement Achieves the Same Solution as an AncestralcisElement During Thiamine Starvation inCandida glabrata

Light-Induced Stress as a Primary Evolutionary Driver of Eye Origins

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