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Mammoth Genome Analysis Points to Pre-Extinction Genome Declines

Woolly mammoths

NEW YORK (GenomeWeb) – An analysis of available ancient genome sequences suggests that the genome of the woolly mammoth, Mammuthus primigenius, began taking on ever more potentially deleterious mutations as populations dwindled and the species got closer to extinction — a finding that may have implications for recognizing species at risk and implementing appropriate conservation measures.

"There is a long history of theoretical work about how genomes might change in small populations," Rebekah Rogers, an integrative biology researcher at the University of California, Berkeley, said in a statement. "Here, we got a rare chance to look at snapshots of genomes 'before' and 'after' a population decline in a single species."

Rogers and co-author Montgomery Slatkin, also based at UC Berkeley, analyzed available genome sequences from a 45,000-year-old mammoth specimen from mainland Siberia, representing a point in time when the mammoth population remained robust. They compared those sequences to ones from a 4,300-year-old mammoth from a miniscule Wrangel Island population that endured after mainland populations disappeared. The mammoth is estimated to have gone extinct 3,700 years ago.

Compared to the older mammoth genome and to available elephant sequences, the team saw a jump in gene-altering deletions and retrogenes in the Wrangel Island mammoth genome, along with new point mutations predicted to upend protein function. The apparent "genomic meltdown" in the waning island population included pseudogenized olfactory genes, along with a loss of genes coding for urinary proteins related to elephant mate choice, and mutations in genes implicated in mammoth coat features, the researchers noted.

"These data bear the signature of genomic meltdown in small populations, consistent with nearly-neutral genome evolution," Rogers and Slatkin wrote in their PLOS Genetics paper. "They furthermore suggest large numbers of detrimental variants collecting in pre-extinction genomes, a warning for continued efforts to protect current endangered species with small population sizes."

For the new study, the pair set out to characterize genetic variants, deletions, point mutations, and more using existing genome sequence data for the Oimyakon mammoth and the Wrangel mammoth, sequenced to average depths of 11-fold and 17-fold coverage by the Swedish Museum of Natural History's Love Dalén and colleagues for a 2015 study in Current Biology.

When they compared these sequences to sequences from an Indian elephant and an African bush elephant reference genome, the researchers found significant differences between the two woolly mammoth genomes. The Wrangel Island mammoth genome contained more overall deletions, gene deletions, retrogene content, and stop codon-causing point mutations relative to the genome of the Oimyakon mammoth, for example.

The team considered the biological effects of some of these new mutations, while placing the genomic changes into a broader context by considering them in relation to known mammoth population patterns.

A rise in deletions was also detected in the genome of the Indian elephant, albeit to a lesser extent, reflecting declines in that animal's population, the researchers reported, pointing to the possibility of tapping genomic data for future conservation efforts in the Indian elephant and other species.

"Although compensatory mutations might conceivably correct for some detrimental mutations, with small effective population sizes, adaptation through both new mutation and standing variation may be severely limited," Rogers and Slatkin concluded. "Thus, we might expect genomes affected by genomic meltdown to show lasting repercussions that will impede population recovery."