In other species: woodpecker finch , large cactus finch , small ground finch , large ground finch , common cactus finch , sharp-beaked ground finch , small tree finch , large tree finch , medium tree finch , Cocos finch , mangrove finch , Española cactus finch & Genovesa ground finch

Possibly relevant human trait(s) and/or gene(s) (MIM number): 611740 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2021

Species-specific description: Enbody et al. (2021) "report a combined field and molecular-genetic investigation of a nestling beak color polymorphism in Darwin's finches. ... we show that the polymorphism arose in the Galápagos half a million years ago through a mutation associated with regulatory change in the BCO2 gene and is shared by 14 descendant species."

History: The beak colour polymorphism was first reported by Grant et al. (1979).

Inheritance: Grant and Grant (2014) reported that yellow beak is a recessive trait.

Mapping: Enbody et al. (2021): “We sequenced whole genomes at low coverage of 456 [Geospiza scandens and G. fortis] individuals of known phenotype …. We generated genotype likelihoods … and conducted an association analysis….We discovered a small region on chromosome 24 harboring a region strongly associated with the yellow phenotype overlapping the carotenoid-cleaving beta-carotene oxygenase 2 gene.”

Molecular basis: After an exhaustive analysis, Enbody et al. (2021) identified a single exonic SNP (chr24:6,166,878G>A) which leads to a synonymous change 32 bp into exon 4 of the positional candidate gene BCO2 as likely causal variant. BCO2 is known to control the yellow skin phenotype in domestic chicken (see OMIA001449-9031: Skin/shank colour, yellow in Gallus gallus).

“The synonymous mutation associated with the yellow morph has an uncertain functional consequence” and the authors acknowledge that they “cannot completely exclude the possibility that this synonymous mutation may be linked to one or several unidentified causal variants.”

However, compelling evidence is provided to support the conclusion that the variant is causal and two possible mechanism are discussed. Firstly, the variant “changes the highest frequency valine codon to the least abundant in the finch genome … [and it is known that] codon usage can be under strong selection and may have functional consequences on translation, RNA stability, and transcription.” Secondly, the authors “found that yellow homozygotes showed significantly lower BCO2 expression compared to pink homozygotes in the upper beak of developing embryos … that were sourced from a variety of different species and islands. … Differences in expression between the two alleles, and in the absence of alternative splice variants … , raise the possibility that the synonymous change alters transcription factor binding affinity in exon 4.”

Associated gene: