The β-casein in camels: molecular characterization of the CSN2 gene, promoter analysis and genetic variability

• The camel β-casein gene and its promoter region were sequenced and characterized.
• 46 polymorphic sites were detected. The SNP g.2126A>G falls within the TATA-box.
• The SNP c.666GMet>AIle identifies the first protein variation at the camel β-casein.
• 5 interspersed elements have been found. One LINE is unique of the camel CSN2 gene.
• microRNA sequences were indicated and putative bio-active peptides identified.

The β-casein is the most abundant protein in camel milk and its encoding gene (CSN2) is considered in other species a ‘major’ gene for the presence of alleles associated to different level of expression. In the present paper, we report for the first time the characterization of the nucleotide sequence of the whole β-casein-encoding gene (CSN2) plus 2141 bp at the 5′-flanking region in Camelus dromedarius. The promoter region and the complete cDNA are also provided for the first time in Camelus bactrianus. The gene is spread over 7.8 kb and consists of 9 exons varying in length from 24 bp (exon 5) to 519 bp (exon 7), and 8 introns from 95 bp (intron 5) to 1950 bp (intron 1). The composite response element (CoRE) region was identified in the promoter, whereas the presence of mature microRNA sequences improves the knowledge on the factors putatively involved in the gene regulation. A total of 46 polymorphic sites have been detected. The transition g.2126A>G falls within the TATA-box of dromedary CSN2 promoter with a putative influence on the transcription factor binding activity. The frequency of the G allele is 0.35 in a population of 180 she-camels belonging to 4 different ecotypes. In the same population, a conservative SNP (g.4175C>A) was found at the codon 7 of the signal peptide, whereas a comparative analysis with a cDNA sequence available in the database evidenced a missense SNP (g.4180TLeu> GArg) at exon 2. Four SNPs were found in the bactrian camel. The SNP c.666G>A is responsible for the amino acid change Met201 → Ile and it represents the first missense allele at the β-casein in camels. Finally, five interspersed repeated elements were identified at intronic level, whereas the presence of putative bio-functional peptides belonging to ACE-inhibitor and anti-oxidative families confirms the potential protective role of the camel milk for the human nutrition.