FOXP in Tetrapoda: Intrinsically Disordered Regions, Short Linear Motifs and their evolutionary significance

Viscardi, Lucas Henriques; Tovo‐Rodrigues, Luciana; Paré, Pamela; Fagundes, Nelson J. R.; Salzano, Francisco M.; Paixão‐Côrtes, Vanessa Rodrigues; Bau, Claiton H.D.; Bortolini, María Cátira

doi:10.1590/1678-4685-gmb-2016-0115

Cited by 3 publications

(1 citation statement)

References 57 publications

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“…Interesting perspectives could arise by comparing animal studies with phenotypic analyses of human FOXP1 mutations associated with speech and language deficits ( Sollis et al, 2016 , 2017 ) but also autism spectrum disorder (ASD) associated variation in sensory feedback processing ( Marco et al, 2011 ). Given that vocal learning progresses in stages and that FoxP1 and FoxP2 have diverse downstream functions ( Vernes et al, 2011 ; Mendoza and Scharff, 2017 ; Viscardi et al, 2017 ), both perceptual and productive components of vocal learning could be affected independently or simultaneously.…”

Section: Discussionmentioning

confidence: 99%

Effects of Cortical FoxP1 Knockdowns on Learned Song Preference in Female Zebra Finches

Heim

Fisher

Scharff

et al. 2023

eNeuro

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The search for molecular underpinnings of human vocal communication has focused on genes encoding forkhead-box transcription factors, as rare disruptions of FOXP1, 2 and 4 have been linked to disorders involving speech and language deficits. In male songbirds, an animal model for vocal learning, experimentally altered expression levels of these transcription factors impair song production learning. The relative contributions of auditory processing, motor function or auditory-motor integration to the deficits observed after different FoxP manipulations in songbirds are unknown. To examine the potential effects on auditory learning and development, we focused on female zebra finches (Taeniopygia guttata) that do not sing but develop song memories, which can be assayed in operant preference tests. We tested whether the relatively high levels ofFoxP1expression in forebrain areas implicated in female song preference learning are crucial for the development and/or maintenance of this behaviour. Juvenile and adult female zebra finches received FoxP1 knockdowns targeted to HVC (proper name) or to the caudomedial mesopallium (CMM). Irrespective of target site and whether the knockdown took place before (juveniles) or after (adults) the sensitive phase for song memorisation, all groups preferred their tutor’s song. However, adult females with FoxP1 knockdowns targeted at HVC showed weaker motivation to hear song and weaker song preferences than sham-treated controls, while no such differences were observed after knockdowns in CMM or in juveniles. In summary, FoxP1 knockdowns in the cortical song nucleus HVC were not associated with impaired tutor song memory but reduced motivation to actively request tutor songs.Significance statementVocal production learning in humans and birds requires auditory memory formation and recall. HumanFOXP1mutations are associated with broad neurodevelopmental disorders including speech and language impairments. In juvenile male zebra finches knockdowns of the avian ortholog, FoxP1, in regions relevant for song learning impair song copying. Whether FoxP1 is relevant for auditory learning is unknown. Studies in non-singing females make it possible to test this. We report that FoxP1 knockdowns in CMM during development and adulthood do not affect auditory learning, while knockdowns in the premotor nucleus HVC in adult but not juvenile female zebra finches reduce tutor song preference and motivation to receive playbacks. These findings support roles of FoxP1 in auditory perception and motivation to hear song.

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Section: Discussionmentioning

confidence: 99%

Effects of Cortical FoxP1 Knockdowns on Learned Song Preference in Female Zebra Finches

Heim

Fisher

Scharff

et al. 2023

eNeuro

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Sequence conservation of protein binding segments in intrinsically disordered regions

Ota

Fukuchi

2017

Biochemical and Biophysical Research Communications

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Intrinsically disordered proteins are proteins with intrinsically disordered regions (IDRs) that do not adopt a globular structure in their free state. IDRs have unique regions having protein-binding segments of which play pivotal roles in many biological processes. The binding sites in IDRs are heterogeneous in terms of their sequence conservation: some are conserved and others are not. We have been running a database of intrinsically disordered proteins, IDEAL, and collecting such binding segments, which are called protean segments (ProSs), within it. In this study, we compared the sequence conservation of ProSs, structural domains (SDs), and IDRs other than ProSs (non-ProSs) and found that i) functionally constrained residues in ProSs tend to be conserved, ii) the distribution of conservation scores of ProSs is similar to those of SDs but not non-ProSs, and iii) ProSs found in human proteins are mostly conserved only in vertebrates. These results indicate that the conservation patterns in ProSs principally follow the general rules found in SDs. However, we need to consider evolutionary distance when comparing IDR sequences because ProSs can readily emerge and disappear over the course of protein evolution. Moreover, many ProSs may remain to be identified, which may account for the heterogeneity of the sequence conservation of IDRs.

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Evolution of SLiM-mediated hijack functions in intrinsically disordered viral proteins

Glavina

Palopoli

Chemes

2022

Essays in Biochemistry

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Viruses and their hosts are involved in an ‘arms race’ where they continually evolve mechanisms to overcome each other. It has long been proposed that intrinsic disorder provides a substrate for the evolution of viral hijack functions and that short linear motifs (SLiMs) are important players in this process. Here, we review evidence in support of this tenet from two model systems: the papillomavirus E7 protein and the adenovirus E1A protein. Phylogenetic reconstructions reveal that SLiMs appear and disappear multiple times across evolution, providing evidence of convergent evolution within individual viral phylogenies. Multiple functionally related SLiMs show strong coevolution signals that persist across long distances in the primary sequence and occur in unrelated viral proteins. Moreover, changes in SLiMs are associated with changes in phenotypic traits such as host range and tropism. Tracking viral evolutionary events reveals that host switch events are associated with the loss of several SLiMs, suggesting that SLiMs are under functional selection and that changes in SLiMs support viral adaptation. Fine-tuning of viral SLiM sequences can improve affinity, allowing them to outcompete host counterparts. However, viral SLiMs are not always competitive by themselves, and tethering of two suboptimal SLiMs by a disordered linker may instead enable viral hijack. Coevolution between the SLiMs and the linker indicates that the evolution of disordered regions may be more constrained than previously thought. In summary, experimental and computational studies support a role for SLiMs and intrinsic disorder in viral hijack functions and in viral adaptive evolution.

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FOXP in Tetrapoda: Intrinsically Disordered Regions, Short Linear Motifs and their evolutionary significance

Cited by 3 publications

References 57 publications

Effects of Cortical FoxP1 Knockdowns on Learned Song Preference in Female Zebra Finches

Effects of Cortical FoxP1 Knockdowns on Learned Song Preference in Female Zebra Finches

Sequence conservation of protein binding segments in intrinsically disordered regions

Evolution of SLiM-mediated hijack functions in intrinsically disordered viral proteins

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