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Koala Genome Sequencing Identifies Novel Genes, Offers Data to Aid Conservation Efforts

NEW YORK (GenomeWeb) – Australian researchers have sequenced the koala genome, and the data they gathered could aid in the animal's conservation.

Koalas, members of the marsupial family, are listed as vulnerable as they are threatened by both habitat loss and disease — about half of koalas are infected with chlamydia. Their numbers are expected to fall by about 50 percent in the next 20 years.

Researchers led by the University of Sydney's Katherine Belov and her colleagues sequenced and assembled the koala genome using a combination of long-read Pacific Biosciences sequencing, Illumina short-read sequencing, and BioNano optical maps. As they reported in Nature Genetics today, they uncovered expansions within the cytochrome P450 gene family that could enable the koala to eat its specialized eucalyptus diet that would otherwise poison many other mammals, and also found novel lactation proteins that may help young koalas develop in the pouch. Additionally, they identified genes involved in the koala response to chlamydia. 

"The genome provides a springboard for the conservation of this biologically unique species," Belov said in a statement.

Preliminary results from the koala genome project were described at the 2015 Plant and Animal Genome conference.

In this study, the researchers sequenced the koala genome to 57.3-fold coverage using the PacBio platform. They generated a 3.42-gigabase genome assembly using the genome assembler FALCON, polished the assembly using Illumina short reads, and created scaffolds based on BioNano optical maps. From their new assembly, the researchers identified 26,558 koala genes, including 6,124 protein-coding genes that belonged to 2,118 gene families.

The researchers uncovered two large expansions affecting the cytochrome P450 gene family, which is involved in metabolizing a range of compounds. This region, they found, underwent tandem duplication within the koala genome and is under purifying selection, though individual CYP codons have undergone periodic diversifying selection. In a transcriptome analysis of two koalas, the researchers found that these CYP2C genes were highly expressed in the liver and could be involved in detoxifying secondary metabolites, like those produced by eucalyptus.

Koala young, however, are reliant on milk produced by their mothers as they are born after 34 days to 36 days of gestation and spend the next six months to seven months in their mothers' pouch. By combining koala genome sequence data with mammary transcriptome and milk proteome data, the researchers teased out key genes for koala milk. In particular, they uncovered four late lactation protein genes that are linked to trichosurin and β-lactoglobulin that could enable koalas to modulate composition of milk during the course of development to match the joeys' needs. They also identified a novel marsupial milk gene that appears to have an antimicrobial role.

Belov and her colleagues also compared the transcriptomes of koalas with and without ocular chlamydia, and found 1,508 genes that are upregulated and 685 that are downregulated during infection — including ones involved in leukocyte infiltration and proinflammatory mediators. The researchers said that this, in conjunction with their genome assembly's coverage of major histocompatibility complex, T cell receptor, and immunoglobulin genes, could guide vaccine development.

By folding in other koala sequences, the researchers also explored koala demographic history. They found that the animals underwent a population expansion following their appearance in the fossil record about 350,000 years ago, but experienced a sharp population decline about 30,000 years to 40,000 years ago, as did many other Australian species, especially megafauna. They noted that current populations vary in genetic diversity as southern koalas exhibit low genetic diversity, while northern populations have high genetic diversity.

"Our next efforts must be in the application of these findings to genetically manage koala populations, advance the treatment of the diseases affecting koalas, with the goal of conserving this very important species," Rebecca Johnson, director of the Australian Museum Research Institute, added in a statement.