McLennan, E. A. | Search bioRxiv

bioRxiv2025

Inbreeding and resultant homozygosity across key inflammation and DNA repair genes linked to chlamydial infection in New South Wales koalas

Inbreeding and resultant homozygosity can reduce genetic diversity and increase disease susceptibility. Koalas (Phascolarctos cinereus) are one species suffering genomic diversity loss and inbreeding and concurrent significant disease pressure (particularly chlamydiosis). Using 259 whole genomes with a pathogen sampling regime we identify potential links between inbreeding, genome-wide variation and chlamydial infection. We found a general trend of reduced genomic diversity and increased inbreeding from north to south across six sites in New South Wales. A genome-wide association study of 153 individuals from sites with known Chlamydia pecorum presence were used to investigate the potential relationship between inbreeding and infection. Chlamydia positive individuals (average FH = 0.026) were significantly more inbred than Chlamydia negative individuals (average FH= -0.0051) (t = - 2.31, df = 151, p-value = 0.022). We identified several genes involved in host-pathogen interactions and DNA mismatch repair within in runs of homozygosity that were unique to Chlamydia positive individuals. Interestingly, populations considered putatively Chlamydia-free had similar allele frequencies across candidate loci as Chlamydia positive individuals. Combined with gene flow analyses, this result suggests that isolation may have protected these populations more than harbouring alleles conferring infection resilience and supports the concept that disease should be carefully considered in any conservation measures that increase connectivity or translocations. Our genome-wide approach has identified several avenues for investigations into the pathogenesis of Chlamydia infection and chlamydiosis. We showcase the value of high-quality re-sequenced genomes for understanding the implications of inbreeding, genomic diversity loss, and infection susceptibility, all universal problems for threatened species.

genomics↗

bioRxiv2025

Mutation rate estimate and population genomic analysis reveals decline of koalas prior to human arrival

The koala (Phascolarctos cinereus), an iconic Australian marsupial, has experienced substantial historical and contemporary population declines. Identifying the drivers of these declines has been hindered by limited genomic data and by uncertainty regarding the koala mutation rate. Here, we provide the first direct estimate of the koala mutation rate, based on four parent-offspring trios, yielding a mean of 6.12x10{square}{square} mutations per base pair per generation (95% confidence interval: 5.03-7.45x10{square}{square}). Using this estimate of the rate, we reconstructed the demographic history of koalas using 458 whole-genome sequences sampled across their entire range. Our results refine the estimated timing of past changes in population size, suggesting a large decline beginning [~]100 kya, before the arrival of modern humans in Australia. The koala population then split into five genetic populations 6-30 kya, which are now spread across >3500 km on the east coast of Australia. We also use the koala mutation rate to infer recombination maps for each population, confirming lower recombination rates in marsupials than in eutherian mammals. These findings provide critical insights into the evolutionary history of koalas, while highlighting the impact of using species-specific evolutionary rates in the inference of demographic histories and recombination landscapes. Our estimates of the genome-wide mutation rate and population-specific recombination maps for koalas provide valuable resources for future evolutionary and conservation analyses of marsupials.

evolutionary biology↗