Slow recovery from inbreeding depression generated by the complex genetic architecture of segregating deleterious mutations

Abstract

The deleterious effects of inbreeding have been of extreme importance to evolutionary biology, but it has been difficult to characterize the complex interactions between genetic constraints and selection that lead to fitness loss and recovery after inbreeding. Viruses, bacteria, and the selfing nematode Caenorhabditis elegans have been shown to be capable of rapid recovery from the fixation of novel deleterious mutation, however the potential for fitness recovery from fixation of segregating variation under inbreeding in outcrossing organisms is poorly understood. C. remanei is an outcrossing relative of C. elegans with high polymorphic variation and extreme inbreeding depression. Here we sought to characterize changes C. remanei in patterns of genomic diversity after ∼30 generations of inbreeding via brother-sister mating followed by several hundred generations of recovery at large population size. As expected, inbreeding led to a large decline in reproductive fitness, but unlike results from mutation accumulation experiments, recovery from inbreeding at large populations sizes generated only very moderate recovery in fitness after 300 generations. At the genomic level, we found that while 66% of ancestral segregating SNPs were fixed in the inbred population, this was far fewer than expected under neutral processes. Under recovery, 36 SNPs across 30 genes involved in alimentary, muscular, nervous and reproductive systems changed reproducibly across all replicates, indicating that strong selection for fitness recovery does exist but is likely mutationally limited due to the large number of potential targets. Our results indicate that recovery from inbreeding depression via new compensatory mutations is likely to be constrained by the large number of segregating deleterious variants present in natural populations, limiting the capacity for rapid evolutionary rescue of small populations. Impact Summary Inbreeding is defined as mating between close relatives and can have a large effect on the genetic diversity and fitness of populations. This has been recognized for over 100 years of study in evolutionary biology, but the specific genomic changes that accompany inbreeding and the loss of fitness are still not known. Evolutionary theory predicts that inbred populations lose fitness through the fixation of many deleterious alleles and it is not known if populations can recover fitness after prolonged periods of inbreeding and deleterious fixations, or how long recovery may take. These questions are particularly important for wild populations experiencing declines. In this study we use laboratory populations of the nematode worm Caenorhabditis remanei to analyze the loss of fitness and genomic changes that accompany inbreeding via brother-sister mating, and to track the populations as they recover from inbreeding at large population size over 300 generations. We find that: Total progeny decreased by 65% after inbreeding There were many nucleotides in the genome that remained heterozygous after inbreeding There was an excess of inbreeding-resistant nucleotides on the X chromosome The number of progeny remained low after 300 generations of recovery from inbreeding 30 genes changed significant in allele frequency during recovery, including genes involved in the alimentary, muscular, nervous and reproductive systems Together, our results demonstrate that recovery from inbreeding is difficult, likely due to the fixation of numerous deleterious alleles throughout the genome.