RT Journal Article
SR Electronic
T1 Accumulation and functional architecture of deleterious genetic variants during the extinction of Wrangel Island Mammoths
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 137455
DO 10.1101/137455
A1 Erin Fry
A1 Sun K. Kim
A1 Sravanthi Chigurapti
A1 Katelyn M. Mika
A1 Aakrosh Ratan
A1 Alexander Dammermann
A1 Brian J. Mitchell
A1 Webb Miller
A1 Vincent J. Lynch
YR 2017
UL http://biorxiv.org/content/early/2017/05/14/137455.abstract
AB Woolly mammoths were among the most abundant cold adapted species during the Pleistocene. Their once large populations went extinct in two waves, an end-Pleistocene extinction of continental populations1-4 followed by the mid-Holocene extinction of relict populations on St. Paul Island ∼5,600 years ago5 and Wrangel Island ∼4,000 years ago1-4. Population and conservation genetics theory predicts that deleterious alleles will accumulate as populations decline, leading to downward spiral of declining population size and fitness ending in extinction (mutational meltdown). While the extinction of Wrangel Island mammoths was preceded by prolonged demographic decline, reduced population size and genetic diversity, recurrent inbreeding, and the fixation of deleterious alleles3,4,6-8, the functional consequences of these processes are unclear. Here we show that the extinction of Wrangel Island mammoths was accompanied by an accumulation of deleterious mutations that are predicted to cause diverse behavioral and developmental defects. Resurrecting and functional characterization of Wrangel Island mammoth genes with putative deleterious substitutions identified both loss and gain of function mutations associated with ciliopathies, oligozoospermia and reduced fertility, and neonatal diabetes. These results indicate that last mammoths likely suffered from genetic disease that reduced fitness and directly contributed to their extinction.