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1.
bioRxiv ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38948816

RESUMO

Understanding the phenotypic consequences of naturally occurring genetic changes, as well as their impact on fitness, is fundamental to understanding how organisms adapt to an environment. This is critical when genetic variants have pleiotropic effects, as determining how each phenotype impacted by a gene contributes to fitness is essential to understand how and why traits have evolved. A striking example of a pleiotropic gene contributing to trait evolution is the oca2 gene, coding mutations in which underlie albinism and reductions of sleep in the blind Mexican cavefish, Astyanax mexicanus. Here, we characterize the effects of mutations in the oca2 gene on larval prey capture. We find that when conspecific surface fish with engineered mutations in the oca2 allele are hunting, they use cave-like, wide angle strikes to capture prey. However, unlike cavefish or surface fish in the dark, which rely on lateral line mediated hunting, oca2 mutant surface fish use vision when striking at prey from wide angles. Finally, we find that while oca2 mutant surface fish do not outcompete pigmented surface siblings in the dark, pigmented fish outcompete albino fish in the light. This raises the possibility that albinism is detrimental to larval feeding in a surface-like lighted environment, but does not have negative consequences for fish in cave-like, dark environments. Together, these results demonstrate that oca2 plays a role in larval feeding behavior in A. mexicanus. Further, they expand our understanding of the pleiotropic phenotypic consequences of oca2 in cavefish evolution.

2.
Curr Biol ; 31(16): 3694-3701.e4, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34293332

RESUMO

Adaptation to novel environments often involves the evolution of multiple morphological, physiological, and behavioral traits. One striking example of multi-trait evolution is the suite of traits that has evolved repeatedly in cave animals, including regression of eyes, loss of pigmentation, and enhancement of non-visual sensory systems.1,2 The Mexican tetra, Astyanax mexicanus, consists of fish that inhabit at least 30 caves in Mexico and ancestral-like surface fish that inhabit the rivers of Mexico and southern Texas.3 Cave A. mexicanus are interfertile with surface fish and have evolved a number of traits, including reduced pigmentation, eye loss, and alterations to behavior.4-6 To define relationships between different cave-evolved traits, we phenotyped 208 surface-cave F2 hybrid fish for numerous morphological and behavioral traits. We found differences in sleep between pigmented and albino hybrid fish, raising the possibility that these traits share a genetic basis. In cavefish and other species, mutations in oculocutaneous albinism 2 (oca2) cause albinism.7-12 Surface fish with mutations in oca2 displayed both albinism and reduced sleep. Further, this mutation in oca2 fails to complement sleep loss when surface fish harboring this engineered mutation are crossed to independently evolved populations of albino cavefish with naturally occurring mutations in oca2. Analysis of the oca2 locus in wild-caught cave and surface fish suggests that oca2 is under positive selection in 3 cave populations. Taken together, these findings identify oca2 as a novel regulator of sleep and suggest that a pleiotropic function of oca2 underlies the adaptive evolution of albinism and sleep loss.


Assuntos
Albinismo , Characidae , Proteínas de Peixes/genética , Sono , Animais , Evolução Biológica , Characidae/genética , Olho , Pigmentação/genética
3.
RNA ; 27(2): 221-233, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33219089

RESUMO

During their maturation, nascent 40S subunits enter a translation-like quality control cycle, where they are joined by mature 60S subunits to form 80S-like ribosomes. While these assembly intermediates are essential for maturation and quality control, how they form, and how their structure promotes quality control, remains unknown. To address these questions, we determined the structure of an 80S-like ribosome assembly intermediate to an overall resolution of 3.4 Å. The structure, validated by biochemical data, resolves a large body of previously paradoxical data and illustrates how assembly and translation factors cooperate to promote the formation of an interface that lacks many mature subunit contacts but is stabilized by the universally conserved methyltransferase Dim1. We also show how Tsr1 enables this interface by blocking the canonical binding of eIF5B to 40S subunits, while maintaining its binding to 60S. The structure also shows how this interface leads to unfolding of the platform, which allows for temporal regulation of the ATPase Fap7, thus linking 40S maturation to quality control during ribosome assembly.


Assuntos
Adenilato Quinase/genética , Regulação Fúngica da Expressão Gênica , Metiltransferases/genética , Proteínas Nucleares/genética , Nucleosídeo-Trifosfatase/genética , Proteínas Ribossômicas/genética , Subunidades Ribossômicas Maiores de Eucariotos/genética , Subunidades Ribossômicas Menores de Eucariotos/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Adenilato Quinase/química , Adenilato Quinase/metabolismo , Sítios de Ligação , Metiltransferases/química , Metiltransferases/metabolismo , Modelos Moleculares , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Nucleosídeo-Trifosfatase/química , Nucleosídeo-Trifosfatase/metabolismo , Biogênese de Organelas , Ligação Proteica , Biossíntese de Proteínas , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Proteínas Ribossômicas/química , Proteínas Ribossômicas/metabolismo , Subunidades Ribossômicas Maiores de Eucariotos/metabolismo , Subunidades Ribossômicas Maiores de Eucariotos/ultraestrutura , Subunidades Ribossômicas Menores de Eucariotos/metabolismo , Subunidades Ribossômicas Menores de Eucariotos/ultraestrutura , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo
4.
In. Faculty of Medical Sciences, The University of the West Indies. Faculty of Medical Sciences Students Research Day 2022. , , . , graf.
Não convencional em Inglês | MedCarib | ID: biblio-1516371

RESUMO

Untreated cataract worsens over time which can result in severe vision impairment, leading to blindness thereby contributing to the limitations in the overall functioning of an individual. Cataract extraction can greatly improve one's vision and by extension quality of life (QoL). However, the uptake of cataract surgery is affected by barriers such as affordability, and poor accessibility and availability (AU)


Assuntos
Humanos , Adulto , Pessoa de Meia-Idade
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