Taking a color photo: A homozygous 25-bp deletion in Bace2 may cause brown- and- white coat color in giant pandas

• 成果类型: Article
• 署名作者: Guan, Dengfeng; Sun, Shuyan; Song, Lingyun; Zhao, Pengpeng; Nie, Yonggang; Huang, Xin; Zhou, Wenliang; Yan, Li; Lei, Yinghu; Hu, Yibo; Wei, Fuwen
• 署名单位: Chinese Academy of Sciences; Institute of Zoology, CAS; Jiangxi Agricultural University; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Southern Marine Science & Engineering Guangdong Laboratory; Southern Marine Science & Engineering Guangdong Laboratory (Guangzhou)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12387
• DOI: 10.1073/pnas.2317430121
• 发表日期: 2024-03-12
• 关键词: selection; pmel

摘要

Brown- and - white giant pandas (hereafter brown pandas) are distinct coat color mutants found exclusively in the Qinling Mountains, Shaanxi, China. However, its genetic mechanism has remained unclear since their discovery in 1985. Here, we identified the genetic basis for this coat color variation using a combination of field ecological data, population genomic data, and a CRISPR-Cas9 knockout mouse model. We de novo assembled a long- read - based giant panda genome and resequenced the genomes of 35 giant pandas, including two brown pandas and two family trios associated with a brown panda. We identified a homozygous 25 - bp deletion in the first exon of Bace2, a gene encoding amyloid precursor protein cleaving enzyme, as the most likely genetic basis for brown- and - white coat color. This deletion was further validated using PCR and Sanger sequencing of another 192 black giant pandas and CRISPR-Cas9 edited knockout mice. Our investigation revealed that this mutation reduced the number and size of melanosomes of the hairs in knockout mice and possibly in the brown panda, further leading to the hypopigmentation. These findings provide unique insights into the genetic basis of coat color variation in wild animals. Significance Coat color variation is one of the most diverse traits in wild animals. The giant pandas can have a color photo because of the occurrence of brown pandas. However, the genetic basis of the brown- and - white coat color has remained elusive in the past about four decades. We identified a homozygous 25 - bp deletion in the first exon of Bace2 as the most likely genetic basis for brown- and - white coat color variation in giant pandas. Our study provides unique insights into the genetic basis of coat color variation in wild animals and will guide scientific breeding of the rare brown pandas.