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Background <p>Melanism in wild felids represents an intriguing evolutionary trait, potentially advantageous under specific ecological conditions, but the genetic basis of this phenotype remains unclear in many populations. Here, we explored melanism in the Indian leopard (<i>Panthera pardus fusca</i>) by integrating whole-genome sequencing with evolutionary and structural analyses.</p> Results <p>We identified a single-point mutation (p.C117F) in the agouti signalling protein (ASIP) gene. Evolutionary analyses indicated signs of positive selection acting on the ASIP locus, while codon usage patterns revealed no impairment in translational efficiency. Computational predictions (SIFT, PROVEAN) classified the mutation as functionally damaging. Structural modelling combined with molecular dynamics simulations revealed significant disruptions in the stability, helical content, and receptor-binding affinity of the mutated ASIP protein compared to the wild type. The mutation notably diminished ASIP’s inhibitory interaction with melanocortin-1 receptor (MC1R), which is crucial for melanogenesis regulation. Machine-learning models differentiated between mutant and wild-type protein structures by analysing molecular features.</p> Conclusions <p>Our results support the conclusion that the p.C117F mutation significantly contributes to melanism in Indian leopards, shedding new light on this trait’s molecular underpinnings and evolutionary history. This study identifies the p.C117F mutation as a key driver of melanism in leopards of the Indian subcontinent, providing mechanistic insight into the evolution of complex phenotypes in non-model species.</p>

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Integrated genomic and structural dissection of melanism in Indian leopard (Panthera pardus fusca)

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月11日

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  • Avijit Ghosh,
  • Sachin Kumar,
  • Paresh Porob,
  • Mukesh Thakur,
  • Malay Shukla,
  • Satish Kumar,
  • Sweta Nidhi,
  • Abhishek Singh

摘要

Background

Melanism in wild felids represents an intriguing evolutionary trait, potentially advantageous under specific ecological conditions, but the genetic basis of this phenotype remains unclear in many populations. Here, we explored melanism in the Indian leopard (Panthera pardus fusca) by integrating whole-genome sequencing with evolutionary and structural analyses.

Results

We identified a single-point mutation (p.C117F) in the agouti signalling protein (ASIP) gene. Evolutionary analyses indicated signs of positive selection acting on the ASIP locus, while codon usage patterns revealed no impairment in translational efficiency. Computational predictions (SIFT, PROVEAN) classified the mutation as functionally damaging. Structural modelling combined with molecular dynamics simulations revealed significant disruptions in the stability, helical content, and receptor-binding affinity of the mutated ASIP protein compared to the wild type. The mutation notably diminished ASIP’s inhibitory interaction with melanocortin-1 receptor (MC1R), which is crucial for melanogenesis regulation. Machine-learning models differentiated between mutant and wild-type protein structures by analysing molecular features.

Conclusions

Our results support the conclusion that the p.C117F mutation significantly contributes to melanism in Indian leopards, shedding new light on this trait’s molecular underpinnings and evolutionary history. This study identifies the p.C117F mutation as a key driver of melanism in leopards of the Indian subcontinent, providing mechanistic insight into the evolution of complex phenotypes in non-model species.