A number of species have recently recovered from near-extinction. Although these species have avoided the immediate extinction threat, their long-term viability remains precarious due to the potential genetic consequences of population declines, which are poorly understood on a timescale beyond a few generations. Woolly mammoths (Mammuthus primigenius) became isolated on Wrangel Island around 10,000 years ago and persisted for over 200 generations before becoming extinct around 4,000 years ago. To study the evolutionary processes leading up to the mammoths\' extinction, we analyzed 21 Siberian woolly mammoth genomes. Our results show that the population recovered quickly from a severe bottleneck and remained demographically stable during the ensuing six millennia. We find that mildly deleterious mutations gradually accumulated, whereas highly deleterious mutations were purged, suggesting ongoing inbreeding depression that lasted for hundreds of generations. The time-lag between demographic and genetic recovery has wide-ranging implications for conservation management of recently bottlenecked populations.

Evolutionary theory predicts that the accumulation of deleterious mutations in asexually reproducing organisms should lead to genomic decay. Clonally reproducing cell lines, i.e., transmissible cancers, when cells are transmitted as allografts/xenografts, break these rules and survive for centuries and millennia. The currently known 11 transmissible cancer lineages occur in dogs (canine venereal tumour disease), in Tasmanian devils (devil facial tumor diseases, DFT1 and DFT2), and in bivalves (bivalve transmissible neoplasia). Despite the mutation loads of these cell lines being much higher than observed in human cancers, they have not been eliminated in space and time. Here, we provide potential explanations for how these fascinating cell lines may have overcome the fitness decline due to the progressive accumulation of deleterious mutations and propose that the high mutation load may carry an indirect positive fitness outcome. We offer ideas on how these host-pathogen systems could be used to answer outstanding questions in evolutionary biology. The recent studies on the evolution of these clonal pathogens reveal key mechanistic insight into transmissible cancer genomes, information that is essential for future studies investigating how these contagious cancer cell lines can repeatedly evade immune recognition, evolve, and survive in the landscape of highly diverse hosts.

Cooperative social behaviors, such as parental care, have long been hypothesized to relax selection leading to the accumulation of genetic variation in populations. Although the idea has been discussed for decades, there has been relatively little experimental work to investigate how social behavior contributes to genetic variation in populations. Here, we investigate how parental care can shape molecular genetic variation in the subsocial insect, Nicrophorus vespilloides. Using whole-genome sequencing of populations that had evolved in the presence or absence of parental care for 30 generations, we show that parental care maintains levels of standing genetic variation. In contrast, under a harsh environment without care, strong directional selection caused a reduction in genetic variation. Furthermore, we show that adaptation to the loss of care is associated with genetic divergence between populations at loci related to stress, morphological development, and transcriptional regulation. These data reveal how social behavior is linked to the genetic processes that shape and maintain genetic diversity within populations, and provides rare empirical evidence for an old hypothesis.

Recessive alleles have been shown to directly affect both human Mendelian disease phenotypes and complex traits. Pedigree studies also suggest that consanguinity results in increased childhood mortality and adverse health phenotypes, presumably through penetrance of recessive mutations. Here, we test whether the accumulation of homozygous, recessive alleles decreases reproductive success in a human population. We address this question among the Namibian Himba, an endogamous agro-pastoralist population, who until very recently practiced natural fertility. Using a sample of 681 individuals, we show that Himba exhibit elevated levels of \"inbreeding,\" calculated as the fraction of the genome in runs of homozygosity (FROH). Many individuals contain multiple long segments of ROH in their genomes, indicating that their parents had high kinship coefficients. However, we do not find evidence that this is explained by first-cousin consanguinity, despite a reported social preference for cross-cousin marriages. Rather, we show that elevated haplotype sharing in the Himba is due to a bottleneck, likely in the past 60 generations. We test whether increased recessive mutation load results in observed fitness consequences by assessing the effect of FROH on completed fertility in a cohort of postreproductive women (n = 69). We find that higher FROH is significantly associated with lower fertility. Our data suggest a multilocus genetic effect on fitness driven by the expression of deleterious recessive alleles, especially those in long ROH. However, these effects are not the result of consanguinity but rather elevated background identity by descent.

Theory predicts that genetic erosion in small, isolated populations of endangered species can be assessed using estimates of neutral genetic variation, yet this widely used approach has recently been questioned in the genomics era. Here, we leverage a chromosome-level genome assembly of an endangered rattlesnake (Sistrurus catenatus) combined with whole genome resequencing data (N = 110 individuals) to evaluate the relationship between levels of genome-wide neutral and functional diversity over historical and future timescales. As predicted, we found positive correlations between genome-wide estimates of neutral genetic diversity (π) and inferred levels of adaptive variation and an estimate of inbreeding mutation load, and a negative relationship between neutral diversity and an estimate of drift mutation load. However, these correlations were half as strong for projected future levels of neutral diversity based on contemporary effective population sizes. Broadly, our results confirm that estimates of neutral genetic diversity provide an accurate measure of genetic erosion in populations of a threatened vertebrate. They also provide nuance to the neutral-functional diversity controversy by suggesting that while these correlations exist, anthropogenetic impacts may have weakened these associations in the recent past and into the future.

\'Living fossils\', that is, ancient lineages of low taxonomic diversity, represent an exceptional evolutionary heritage, yet we know little about how demographic history and deleterious mutation load have affected their long-term survival and extinction risk. We performed whole-genome sequencing and population genomic analyses on Dipteronia sinensis and D. dyeriana, two East Asian Tertiary relict trees. We found large-scale genome reorganizations and identified species-specific genes under positive selection that are likely involved in adaptation. Our demographic analyses suggest that the wider-ranged D. sinensis repeatedly recovered from population bottlenecks over late Tertiary/Quaternary periods of adverse climate conditions, while the population size of the narrow-ranged D. dyeriana steadily decreased since the late Miocene, especially after the Last Glacial Maximum (LGM). We conclude that the efficient purging of deleterious mutations in D. sinensis facilitated its survival and repeated demographic recovery. By contrast, in D. dyeriana, increased genetic drift and reduced selection efficacy, due to recent severe population bottlenecks and a likely preponderance of vegetative propagation, resulted in fixation of strongly deleterious mutations, reduced fitness, and continuous population decline, with likely detrimental consequences for the species\' future viability and adaptive potential. Overall, our findings highlight the significant impact of demographic history on levels of accumulation and purging of putatively deleterious mutations that likely determine the long-term survival and extinction risk of Tertiary relict trees.

Selection varies between categories of individuals, with far-reaching ramifications: Sex-specific selection can impede or accelerate adaptation, and differences in selection between young and old individuals are ultimately responsible for senescence. Here, we measure early- and late-life fitness in adults of both sexes from the Drosophila genetic reference panel and perform quantitative genetic and transcriptomic analyses. Fitness was heritable, showed positive pleiotropy across sexes and age classes, and appeared to be influenced by very large numbers of loci with small effects plus a smaller number with moderate effects. Most loci affected male and female fitness in the same direction; relatively few candidate sexually antagonistic loci were found, though these were enriched on the X chromosome as predicted by theory. The expression level of many genes showed an opposite correlation with fitness in males and females, consistent with unresolved sexual conflict over transcription. The load of deleterious mutations correlated negatively with fitness across genotypes, and we found some evidence for the mutation accumulation (but not the antagonistic pleiotropy) theory of aging.

Dingoes arrived in Australia during the mid-Holocene and are the top-order terrestrial predator on the continent. Although dingoes subsequently spread across the continent, the initial founding population(s) could have been small. We investigated this hypothesis by sequencing the whole genomes of three dingoes and also obtaining the genome data from nine additional dingoes and 56 canines, including wolves, village dogs and breed dogs, and examined the signatures of bottlenecks and founder effects. We found that the nucleotide diversity of dingoes was low, 36% less than highly inbred breed dogs and 3.3 times lower than wolves. The number of runs of homozygosity (RoH) segments in dingoes was 1.6-4.7 times higher than in other canines. While examining deleterious mutational load, we observed that dingoes carried elevated ratios of nonsynonymous-to-synonymous diversities, significantly higher numbers of homozygous deleterious Single Nucleotide Variants (SNVs), and increased numbers of loss of function SNVs, compared to breed dogs, village dogs, and wolves. Our findings can be explained by bottlenecks and founder effects during the establishment of dingoes in mainland Australia. These findings highlight the need for conservation-based management of dingoes and the need for wildlife managers to be cognisant of these findings when considering the use of lethal control measures across the landscape.

Each new human has an expected Ud = 2 - 10 new deleterious mutations. This deluge of deleterious mutations cannot all be purged, and therefore accumulate in a declining fitness ratchet. Using a novel simulation framework designed to efficiently handle genome-wide linkage disequilibria across many segregating sites, we find that rarer, beneficial mutations of larger effect are sufficient to compensate fitness declines due to the fixation of many slightly deleterious mutations. Drift barrier theory posits a similar asymmetric pattern of fixations to explain ratcheting genome size and complexity, but in our theory, the cause is Ud > 1 rather than small population size. In our simulations, Ud ~2 - 10 generates high within-population variance in relative fitness; two individuals will typically differ in fitness by 15-40%. Ud ~2 - 10 also slows net adaptation by ~13%-39%. Surprisingly, fixation rates are more sensitive to changes in the beneficial than the deleterious mutation rate, e.g. a 10% increase in overall mutation rate leads to faster adaptation; this puts to rest dysgenic fears about increasing mutation rates due to rising paternal age.

In efforts to prevent extinction, resource managers are often tasked with increasing genetic diversity in a population of concern to prevent inbreeding depression or improve adaptive potential in a changing environment. The assumption that all small populations require measures to increase their genetic diversity may be unwarranted, and limited resources for conservation may be better utilized elsewhere. We test this assumption in a case study focused on the peregrine falcon (Falco peregrinus), a cosmopolitan circumpolar species with 19 named subspecies. We used whole-genome resequencing to generate over two million single nucleotide polymorphisms (SNPs) from multiple individuals of all peregrine falcon subspecies. Our analyses revealed extensive variation among subspecies, with many island-restricted and nonmigratory populations possessing lower overall genomic diversity, elevated inbreeding coefficients (F ROH)-among the highest reported, and extensive runs of homozygosity (ROH) compared to mainland and migratory populations. Similarly, the majority of subspecies that are either nonmigratory or restricted to islands show a much longer history of low effective population size (N e). While mutational load analyses indicated an increased proportion of homozygous-derived deleterious variants (i.e., drift load) among nonmigrant and island populations compared to those that are migrant or reside on the mainland, no significant differences in the proportion of heterozygous deleterious variants (i.e., inbreeding load) was observed. Our results provide evidence that high levels of inbreeding may not be an existential threat for some populations or taxa. Additional factors such as the timing and severity of population declines are important to consider in management decisions about extinction potential.