Can you tell me what the purpose and hypothesis of this article is please? Its obviously somewhere in the first 2 short paragraphs, but I cant REFINE the purpose. And as for the hypothesis, I know the question they are trying to solve, but im missing where they hypothesized what the outcome would be. Thank you in advance.
Article: Progressive Loss of Function in a Limb Enhancer during Snake Evolution
Distant-acting transcriptional enhancers are a major class of tissue-specific regulatory DNA sequences that has been implicated in morphological evolution in vertebrates. Sequence changes in non-coding regulatory DNA are hypothesized to be a main driver of changes in body shape), but many aspects of this complex inter- play between molecular changes in regulatory sequences and morphological adaptations across the vertebrate tree remain the subject of considerable debate.
In the present study, we utilized a series of recently sequenced snake genomes to study the molecular and functional evolution of a critical limb enhancer in snakes and examine its possible role in limb loss. Our analysis focuses on one of the best-studied verte- brate enhancers, the Zone of Polarizing Activity [ZPA] Regulatory Sequence (ZRS, also known as MFCS1). The ZRS is a limb-specific enhancer of the Sonic hedge- hog (Shh) gene that is located at the extreme distance of nearly one million base pairs from its target promoter. During limb devel- opment, the enhancer is active in the posterior limb bud mesen- chyme, where its activity is critically required for normal limb development in mouse. Single- nucleotide mutations within the ZRS cause limb malformations, such as preaxial polydactyly, in multiple vertebrate species including humans. Surprisingly, we observed that the sequence of this limb enhancer is conserved throughout nearly all examined species in the snake lineage. In basal snakes, which retain vestigial limbs, it is highly conserved, whereas it un- derwent a rapid increase in substitution rate in advanced snakes, in which all skeletal limb structures have disappeared. Consistent with this, we provide evidence that the snake enhancer progres- sively lost its in vivo function as the body plan evolved from basal to advanced snakes. Finally, we identify a specific subset of nucleotide changes within the enhancer that contribute to its functional degeneration in snakes and show in a mouse model that synthetic reintroduction of just one degraded transcription factor binding site is sufficient to recreate the ancestral function and to rescue normal limb formation in vivo.
Can you tell me what the purpose and hypothesis of this article is please? Its obviously somewhere in the first 2 short paragraphs, but I cant REFINE the purpose. And as for the hypothesis, I know the question they are trying to solve, but im missing where they hypothesized what the outcome would be. Thank you in advance.
Article: Progressive Loss of Function in a Limb Enhancer during Snake Evolution
Distant-acting transcriptional enhancers are a major class of tissue-specific regulatory DNA sequences that has been implicated in morphological evolution in vertebrates. Sequence changes in non-coding regulatory DNA are hypothesized to be a main driver of changes in body shape), but many aspects of this complex inter- play between molecular changes in regulatory sequences and morphological adaptations across the vertebrate tree remain the subject of considerable debate.
In the present study, we utilized a series of recently sequenced snake genomes to study the molecular and functional evolution of a critical limb enhancer in snakes and examine its possible role in limb loss. Our analysis focuses on one of the best-studied verte- brate enhancers, the Zone of Polarizing Activity [ZPA] Regulatory Sequence (ZRS, also known as MFCS1). The ZRS is a limb-specific enhancer of the Sonic hedge- hog (Shh) gene that is located at the extreme distance of nearly one million base pairs from its target promoter. During limb devel- opment, the enhancer is active in the posterior limb bud mesen- chyme, where its activity is critically required for normal limb development in mouse. Single- nucleotide mutations within the ZRS cause limb malformations, such as preaxial polydactyly, in multiple vertebrate species including humans. Surprisingly, we observed that the sequence of this limb enhancer is conserved throughout nearly all examined species in the snake lineage. In basal snakes, which retain vestigial limbs, it is highly conserved, whereas it un- derwent a rapid increase in substitution rate in advanced snakes, in which all skeletal limb structures have disappeared. Consistent with this, we provide evidence that the snake enhancer progres- sively lost its in vivo function as the body plan evolved from basal to advanced snakes. Finally, we identify a specific subset of nucleotide changes within the enhancer that contribute to its functional degeneration in snakes and show in a mouse model that synthetic reintroduction of just one degraded transcription factor binding site is sufficient to recreate the ancestral function and to rescue normal limb formation in vivo.
