Dec 16, 2022

Save for later NEW YORK – New research suggests a single-base change that arose nearly 9,400 years ago accounts for black bears with brown fur coloring, a color variation known as the cinnamon morph. As they reported in Current Biology on Friday, the researchers started with whole-genome sequencing on two dozen black bears (Ursus americanus), coupled with shallow genome resequencing on 166 more bears, mapping sequences to a bear reference genome for variant imputation. From there, they performed a genome-wide association analysis on 151 black bears, searching for variants with significant ties to reflectance-based color measurements. In the process, the team identified more than 150 SNP associations, narrowing in on a missense mutation in the pigmentation-related gene TYRP1 that showed the strongest ties to coloring. Bringing in genome resequencing data for six eastern or western black bears, the researchers estimated that those two lineages started to split from one another around 100,000 years ago. The loss-of-function TYRP1 variant, known as R153C, appeared to stem from a lone mutational event in western bears roughly 9,360 years ago, they explained, but continued to expand to new regions with subsequent gene flow between the lineages. The team noted that cinnamon coloring is more common in black bears from the southwestern reaches of the predator's range, where it is suspected of offering more effective camouflage and temperature regulation in the relatively hot, dry environment. "Our analyses indicate that the cinnamon TYRP1 variant arose within the western lineage of U. americanus and likely provided a selective advantage in the southwest," first and corresponding author Emily Puckett, a biological sciences researcher at the University of Memphis, and her colleagues wrote, though their results suggested brown coloring distribution "is being driven by recent and ongoing gene flow, suggesting that cinnamon morphs will increase in frequency within the eastern lineage in the future." With targeted sequencing on TYRP1 and a dozen other pigmentation-related genes in black, brown (U. arctos), or polar (U. maritimus) bears, the team confirmed ties between TYRP1-R153C and color in black bears, identifying another TYRP1 variant known as R114C in some 60 percent of grizzly bears considered. In their subsequent mouse model experiments, the investigators found that the R153C and R114C versions of the TYRP1 gene led to lower pigment levels than wild-type mouse or human versions of the gene when used to add TYRP1 to melan-b cells from hypopigmented mice missing the gene. The team noted that loss-of-function TYRP1 variants have been implicated in a rare form of human albinism most often found in some African and Puerto Rican populations. In bears, meanwhile, such variants appear to be linked to light brown coloring, both in cinnamon morph black bears and in grizzly bears (U. arctos ssp. horribilis. Based on high-performance liquid chromatography-based pigment analyses on black bear and brown bear hair samples, the researchers found that cinnamon-colored black bears and brown bears have similar melanin measurements. Together, their results suggested that these shifts stemmed from reduced black or brown eumelanin pigment levels relative to the red or yellow pheomelanin pigment levels in melanosome cells due to altered protein localization in the presence of variants that prompt misfolding by the TYRP1 gene product. These and other findings from the study "illustrate how Mendelian variation in melanogenesis can underlie iconic phenotypes and inform our understanding of color variation and recent evolution in large carnivores," the authors wrote.