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. 2009 Sep 11:9:232.
doi: 10.1186/1471-2148-9-232.

Genetic variation at hair length candidate genes in elephants and the extinct woolly mammoth

Alfred L Roca  1 , Yasuko Ishida, Nikolas Nikolaidis, Sergios-Orestis Kolokotronis, Stephen Fratpietro, Kristin Stewardson, Shannon Hensley, Michele Tisdale, Gennady Boeskorov, Alex D Greenwood
Affiliations

Genetic variation at hair length candidate genes in elephants and the extinct woolly mammoth

Alfred L Roca et al. BMC Evol Biol. .

Abstract

Background: Like humans, the living elephants are unusual among mammals in being sparsely covered with hair. Relative to extant elephants, the extinct woolly mammoth, Mammuthus primigenius, had a dense hair cover and extremely long hair, which likely were adaptations to its subarctic habitat. The fibroblast growth factor 5 (FGF5) gene affects hair length in a diverse set of mammalian species. Mutations in FGF5 lead to recessive long hair phenotypes in mice, dogs, and cats; and the gene has been implicated in hair length variation in rabbits. Thus, FGF5 represents a leading candidate gene for the phenotypic differences in hair length notable between extant elephants and the woolly mammoth. We therefore sequenced the three exons (except for the 3' UTR) and a portion of the promoter of FGF5 from the living elephantid species (Asian, African savanna and African forest elephants) and, using protocols for ancient DNA, from a woolly mammoth.

Results: Between the extant elephants and the mammoth, two single base substitutions were observed in FGF5, neither of which alters the amino acid sequence. Modeling of the protein structure suggests that the elephantid proteins fold similarly to the human FGF5 protein. Bioinformatics analyses and DNA sequencing of another locus that has been implicated in hair cover in humans, type I hair keratin pseudogene (KRTHAP1), also yielded negative results. Interestingly, KRTHAP1 is a pseudogene in elephantids as in humans (although fully functional in non-human primates).

Conclusion: The data suggest that the coding sequence of the FGF5 gene is not the critical determinant of hair length differences among elephantids. The results are discussed in the context of hairlessness among mammals and in terms of the potential impact of large body size, subarctic conditions, and an aquatic ancestor on hair cover in the Proboscidea.

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Figures

Figure 1
Figure 1
Chronogram showing divergence dates for selected mammalian species. Branches are shown in gray for relatively hairless lineages [28] and in black for taxa with greater hair cover. Lineages that are completely aquatic are italicized. An asterisk indicates domestic species for which mutations in the FGF5 gene have been identified as responsible for long hair phenotypes in one or more breeds [2,5,6,8]. The relationships depicted among taxa, and the divergence dates on the chronogram, are from previously published paleontological [30,31] or genetic [9,10,34,39] studies.
Figure 2
Figure 2
Alignment of FGF5 amino acid sequences determined for elephantids, along with the large splice variants of bovid, human, cat, dog (wolf, not shown, has amino acid sequence identical to dog), and mouse. Exon 2 is lightly shaded while exons 1 and 3 are unshaded. Common and scientific names are shown for all species; laboratory codes are shown for the elephantids (see Methods for information on individual samples). An Asian elephant is used as the reference sequence; identities are shown as dots; differences are shown as the single letter amino acid code that differs from the reference sequence; alignment gaps are shown as dashes. The Indigirka ("Ind") woolly mammoth sequence is distinguished by dark shading. Sequences not obtained for specific individuals are shown with #.
Figure 3
Figure 3
The mammoth FGF5 protein compared to the human FGF5 protein sequence. (A) Pairwise alignment of the FGF5 sequences from human [GenBank:NP_004455] and mammoth (this study). The secondary structure, which is shown above each alignment row, represents the consensus structure as predicted by the SSPro and PHYRE programs. The signal peptide is shown with bold-italic fonts; the position of the G33A forest elephant mutation is depicted with bold-underlined fonts; the solvent exposed loop is shown with italics; the glycine box is shown with underlined font [23]. Black triangles depict O-glycosylation sites and a black diamond is used to depict the N-glycosylation site. The FGF receptor (FGFR) binding sites are shown with # and the heparin binding sites with * [24]. (B) The three-dimensional model of the mammoth FGF5 (violet color) protein. The FGFR and heparin binding sites are depicted using yellow and blue color, respectively. The differences between human and mammoth FGF5 sequences are colored green.
Figure 4
Figure 4
Partial sequence of KRTHAP1 exon 1 of the Indigirka woolly mammoth (Mammuthus primigenius), aligned to respective sequences from savanna elephant (Loxodonta africana) and human (Homo sapiens). For each species, both DNA (above) and amino acid sequences (below, in boldface) are shown. Premature stop codons predicted for the elephantids are indicated (after which no amino acids are shown for them). Mammoth consensus sequence was generated from clones of two independent PCR reactions (not shown); genomic sequences were used for the other two species.
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