Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears

Abstract

Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyper-lipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans.

Fig. 1. Sampling localities

Polar and brown bear distributions are shown in blue and brown shading, respectively. See also Table S2.

Fig. 2. Demographic inference

Joint demographic model for polar bear and North American brown bear populations inferred using the identity by state (IBS) tract method (A). Joint past population is in grey, polar bear in blue and brown bear in brown. Estimated effective population sizes are indicated and the migration rate is in genetic replacements per generation. The recent brown bear population size has been downscaled by a factor of 20, the recent polar bear population size is to scale. (B, C) Distribution of IBS tract length from our observed data (solid line) and from model prediction (dotted line) inferring gene flow from polar bear into brown bear (B) or using a simple isolation-with-migration (IM) model (C), which does not account for past population size changes. There are only two black dotted curves in (C) because the IM model constrains the within-polar bear and within-brown bear tract lengths to be the same. See also Fig. S4B and Table S3.

Fig. 3. Enrichment analysis

Gene Ontology enrichment analysis for putative genes under positive selection in the polar bear lineage. We ranked genes based on their homogeneity test score by first considering genes where the ratio between polymorphisms and divergence was lower in the polar bear than in the brown bear samples. We used the web application GOrilla (http://cbl-gorilla.cs.technion.ac.il) to detect biological process terms enriched with top genes in the ranked list. Blue shading indicates biological categories significantly enriched with genes under positive selection in the polar bear lineage, after correction for multiple tests.

Fig. 4. Positive selection analysis

(A, B) Distribution of the homogeneity test scores for the top-50 genes in polar bear (blue) and brown bear (brown). We compared the observed distribution versus the expected distribution under neutrality, using the demographic model presented in Table S3; (C, D) Predicted functional impact of polar bear-specific protein substitutions. We reported the functional classification and probability of being damaging for polar bear-specific missense mutations located in the top 20 genes under positive selection, according to the two metrics HumanDiv and HumanVar computed by PolyPhen-2. See also Table S7.

Fig. 5. The apoB and LYST protein sequences

The distribution of fixed non-synonymous polar bear mutations (blue arrows) compared to the brown bear, using the giant panda sequence as an outgroup. (A) Mutations predicted to affect protein structure based on apoB alignments across 20 vertebrate species, using the SIFT algorithm (Sim et al., 2012), are indicated with hollow circles on arrows. The grey curve shows the cubic smoothing spline of the amino acid conservation scores; higher scores indicate higher conservation across 20 vertebrate species. The x-axis shows the amino acid position from the N-terminal, the five domains are based on the human apoB sequence (Prassl and Laggner, 2009). (B) The same representation as in panel A, but for the LYST protein sequence. The domains are based on [http://www.ebi.ac.uk/interpro/protein/LYST_HUMAN]. (C) Mapping of polar bear-specific substitutions and Chediak-Higashi syndrome causing variants on the protein structure of LYST N-terminal domain.