Genetic diversity of the major cat allergen, Fel d 1.

Cat allergy affects ∼15% of the US population and can cause severe symptoms, including asthma. The major cat allergen, Fel d 1, drives IgE antibody responses. We conducted a comparative analysis of Fel d 1 genes, and , and investigated structural features of Fel d 1 homologs across the family . The and domestic cat DNA references were used to identify homologous sequences in domestic and exotic cat genomes. Variability of these sequences within or across cat species was analyzed. Comprehensive alignments of Fel d 1 sequences and homologs from 276 domestic or exotic cats identified >100 unique, dissimilar substitutions in the protein sequences across . Selective pressure analyses of 37 exotic cat species revealed that Fel d 1 experienced positive selection, or greater variability over time, in and . Linear regression of the mean pairwise identities of Fel d 1 DNA or protein sequences indicated that the genes largely reflected the evolution of . The Fel d 1 genes are highly variable (41 and 58% of the amino acid residues encoded by and , respectively), suggesting that the biological function of Fel d 1, which is currently unknown, may vary among cat species and/or that Fel d 1 may be nonessential for cats. This is supported by Fel d 1 homology to nonessential proteins and recent evidence of healthy cats with CRISPR-edited genes. Fel d 1 variability could confer an evolutionary advantage for cats by allowing the allergen to bind different physiological ligands.