Possibly relevant human trait(s) and/or gene(s) (MIM number): 613456

Mendelian trait/disorder: no

Mode of inheritance: Multifactorial

Considered a defect: no

Key variant known: no

Key variant is published: no

History: Variation in beak shape and size between species of finches on different islands of the Galapagos archipelago has become one of the textbook examples of evolution. This variation was first noted by Charles Darwin, following his visit to the archipelago in 1835 during the round-the-world voyage of HMS Beagle. Darwin did not mention the variation in the diary he wrote at the time of the visit, but did mention it in his published journal of the voyage (Darwin, 1839): "It is very remarkable that a nearly perfect gradation of structure in this one group can be traced in the form of the beak, from one exceeding in dimensions that of the largest gros-beak, to another differing but little from that of a warbler. [pp. 461-462] . . . I have stated, that in the thirteen species of ground-finches, a nearly perfect gradation may be traced, from a beak extraordinarily thick, to one so fine, that it may be compared to that of a warbler. I very much suspect, that certain members of the series are confined to different islands; therefore, if the collection had been made on any one island, it would not have presented so perfect a gradation. It is clear, that if several islands have each their peculiar species of the same genera, when these are placed together, they will have a wide range of character. But there is not space in this work, to enter on this curious subject. [p. 475]"

By the time of the second edition of this journal, published in 1845, Darwin had more to say on the variation in beak shape and size: "The most curious fact is the perfect gradation in the size of the beaks in the different species of Geospiza, from one as large as that of a hawfinch to that of a chaffinch, and (if Mr. Gould is right in including his sub-group, Certhidea, in the main group), even to that of a warbler. The largest beak in the genus Geospiza is shown in Fig. 1, and the smallest in Fig. 3; but instead of there being only one intermediate species, with a beak of the size shown in Fig. 2, there are no less than six species with insensibly graduated beaks. The beak of the sub-group Certhidea, is shown in Fig. 4. The beak of Cactornis is somewhat like that of a starling; and that of the fourth sub-group, Camarhynchus, is slightly parrot-shaped. Seeing this gradation and diversity of structure in one small, intimately related group of birds, one might really fancy that from an original paucity of birds in this archipelago, one species had been taken and modified for different ends. [pp. 379-380]". The reference to figures relates to a plate in the 1845 journal, illustrating the contrasting beak shapes and sizes of four Galapagos finches.

Interestingly, Darwin makes no mention of Galapagos finches in any edition of Origin of Species, because (despite his earlier surmises above), he never had sufficient information on the available specimens to enable him to draw firm conclusions about evolution. Ironically, it was not until many decades after Darwin's death that sufficient information had been gathered on Galapagos finches (see, e.g., Lack, 1947) to enable them to become a classic textbook example of evolution.

Mapping: A landmark paper by Leif Andersson and colleagues (Lamichhaney et al., 2015), published online on the eve of Darwin's 206th birthday, reports a comparison of whole-genome sequence between "populations that are closely related but show different beak morphology: G.magnirostris and G. conirostris on [the island] Espanola have blunt beaks, whereas G. conirostris on Genovesa and G. difficilis on [the island] Wolf have pointed beaks. . . . Among the 15 most significant regions, six harboured genes previously associated with craniofacial and/or beak development in mammals or birds including calmodulin (CALM), goosecoid homeobox (GSC), retinol dehydrogenase 14 (RDH14),ALXhomeobox 1 (ALX1), fibroblast growth factor 10 (FGF10) and forkhead box C1 (FOXC1)."

Molecular basis: From the results of the comparison of whole-genome sequence described above, Lamichhaney et al. (2015) reported that the highest fixation index between the two groups was observed in a 240-kb region containing the gene ALX1, which "encodes a paired type homeodomain protein that plays a crucial role in development of structures derived from craniofacial mesenchyme, the first branchial arch and the limb bud, and on migration of cranial neural crest cells, highly relevant to beak development. Loss of ALX1 in humans causes disruption of early craniofacial development" (see the link to OMIM 613456 above). Equally importantly, mutations in ALX1 in cats give rise to brachycephaly! (see OMIA 001551-9685).

Consistent with their observation of at least 15 regions of differentiation between the two groups of finches, the authors were careful to note that "A polygenic basis for beak diversity is indicated by our discovery of about 15 regions with strong genetic differentiation between groups of finches with blunt or pointed beaks." Thus, ALX1 is a QTL for beak shape.

The authors conclude: "We present evidence that the ALX1 locus contributes to beak diversity, within and among species. The derived ALX1-B haplotype associated with blunt beaks has a long evolutionary history (hundreds of thousands of years), because its origin predates the radiation of vegetarian, tree and ground finches . . . . This haplotype is fixed or nearly fixed in two ground finches with blunt beaks, G. magnirostris and G. conirostris on Espanola, and it co-segregates with variation in beak shape in G. fortis. . . . Natural selection and introgression affecting this locus have contributed to the diversification of beak shapes among Darwin’s finches and hence to their expanded utilization of food resources on Galapagos."

Associated gene: