Evolution of the Mutation Spectrum Across a Mammalian Phylogeny.

Although evolutionary biologists have long theorized that variation in DNA repair efficacy might explain some of the diversity of lifespan and cancer incidence across species, we have little data on the variability of normal germline mutagenesis outside of humans. Here, we shed light on the spectrum and etiology of mutagenesis across mammals by quantifying mutational sequence context biases using polymorphism data from thirteen species of mice, apes, bears, wolves, and cetaceans. After normalizing the mutation spectrum for reference genome accessibility and k-mer content, we use the Mantel test to deduce that mutation spectrum divergence is highly correlated with genetic divergence between species, whereas life history traits like reproductive age are weaker predictors of mutation spectrum divergence. Potential bioinformatic confounders are only weakly related to a small set of mutation spectrum features. We find that clock-like mutational signatures previously inferred from human cancers cannot explain the phylogenetic signal exhibited by the mammalian mutation spectrum, despite the ability of these signatures to fit each species' 3-mer spectrum with high cosine similarity. In contrast, parental aging signatures inferred from human de novo mutation data appear to explain much of the 1-mer spectrum's phylogenetic signal in combination with a novel mutational signature. We posit that future models purporting to explain the etiology of mammalian mutagenesis need to capture the fact that more closely related species have more similar mutation spectra; a model that fits each marginal spectrum with high cosine similarity is not guaranteed to capture this hierarchy of mutation spectrum variation among species.

Genomic analyses reveal range-wide devastation of sea otter populations.

The genetic consequences of species-wide declines are rarely quantified because the timing and extent of the decline varies across the species' range. The sea otter (Enhydra lutris) is a unique model in this regard. Their dramatic decline from thousands to fewer than 100 individuals per population occurred range-wide and nearly simultaneously due to the 18th-19th century fur trade. Consequently, each sea otter population represents an independent natural experiment of recovery after extreme population decline. We designed sequence capture probes for 50 Mb of sea otter exonic and neutral genomic regions. We sequenced 107 sea otters from five populations that span the species range to high coverage (18-76×) and three historical Californian samples from ~1500 and ~200 years ago to low coverage (1.5-3.5×). We observe distinct population structure and find that sea otters in California are the last survivors of a divergent lineage isolated for thousands of years and therefore warrant special conservation concern. We detect signals of extreme population decline in every surviving sea otter population and use this demographic history to design forward-in-time simulations of coding sequence. Our simulations indicate that this decline could lower the fitness of recovering populations for generations. However, the simulations also demonstrate how historically low effective population sizes prior to the fur trade may have mitigated the effects of population decline on genetic health. Our comprehensive approach shows how demographic inference from genomic data, coupled with simulations, allows assessment of extinction risk and different models of recovery.

Phylogeographic and diversification patterns of the white-nosed coati (Nasua narica): Evidence for south-to-north colonization of North America.

White-nosed coatis (Nasua narica) are widely distributed throughout North, Central, and South America, but the patterns of temporal and spatial diversification that have contributed to this distribution are unknown. In addition, the biogeographic history of procyonid species in the Americas remains contentious. Using sequences from three mitochondrial loci (Cytochrome b, NAHD5 and 16S rRNA; 2201 bp) and genotypes from 11 microsatellite loci, we analyzed genetic diversity to determine phylogeographic patterns, genetic structure, divergence times, and gene flow among Nasua narica populations throughout the majority of the species' range. We also estimated the ancestral geographic range of N. narica and other procyonid species. We found a high degree of genetic structure and divergence among populations that conform to five evolutionarily significant units. The most southerly distributed population (Panama) branched off much earlier (∼3.8 million years ago) than the northern populations (<1.2 million years ago). Estimated gene flow among populations was low and mostly northwards and westwards. The phylogeographic patterns within N. narica are associated with geographic barriers and habitat shifts likely caused by Pliocene-Pleistocene climate oscillations. Significantly, our findings suggest the dispersal of N. narica was south-to-north beginning in the Pliocene, not in the opposite direction during the Pleistocene as suggested by the fossil record, and that the most recent common ancestor for coati species was most likely distributed in South or Central America six million years ago. Our study implies the possibility that the diversification of Nasua species, and other extant procyonid lineages, may have occurred in South America.

Transcriptomic analysis of skin pigmentation variation in the Virginia opossum (Didelphis virginiana).

Skin pigmentation and coat pigmentation are two of the best-studied examples of traits under natural selection given their quantifiable fitness interactions with the environment (e.g., camouflage) and signalling with other organisms (e.g., warning coloration). Previous morphological studies have found that skin pigmentation variation in the Virginia opossum (Didelphis virginiana) is associated with variation in precipitation and temperatures across its distribution range following Gloger's rule (lighter pigmentation in temperate environments). To investigate the molecular mechanism associated with skin pigmentation variation, we used RNA-Seq and quantified gene expression of wild opossums from tropical and temperate populations. Using differential expression analysis and a co-expression network approach, we found that expression variation in genes with melanocytic and immune functions is significantly associated with the degree of skin pigmentation variation and may be underlying this phenotypic difference. We also found evidence suggesting that the Wnt/ß-catenin signalling pathway might be regulating the depigmentation observed in temperate populations. Based on our study results, we present several alternative hypotheses that may explain Gloger's rule pattern of skin pigmentation variation in opossum, including changes in pathogen diversity supporting a pathogen-resistant hypothesis, thermal stress associated with temperate environments, and pleiotropic and epistatic interactions between melanocytic and immune genes.

"Evolution of the mutation spectrum across a mammalian phylogeny".

Little is known about how the spectrum and etiology of germline mutagenesis might vary among mammalian species. To shed light on this mystery, we quantify variation in mutational sequence context biases using polymorphism data from thirteen species of mice, apes, bears, wolves, and cetaceans. After normalizing the mutation spectrum for reference genome accessibility and k -mer content, we use the Mantel test to deduce that mutation spectrum divergence is highly correlated with genetic divergence between species, whereas life history traits like reproductive age are weaker predictors of mutation spectrum divergence. Potential bioinformatic confounders are only weakly related to a small set of mutation spectrum features. We find that clocklike mutational signatures previously inferred from human cancers cannot explain the phylogenetic signal exhibited by the mammalian mutation spectrum, despite the ability of these clocklike signatures to fit each species' 3-mer spectrum with high cosine similarity. In contrast, parental aging signatures inferred from human de novo mutation data appear to explain much of the mutation spectrum's phylogenetic signal when fit to non-context-dependent mutation spectrum data in combination with a novel mutational signature. We posit that future models purporting to explain the etiology of mammalian mutagenesis need to capture the fact that more closely related species have more similar mutation spectra; a model that fits each marginal spectrum with high cosine similarity is not guaranteed to capture this hierarchy of mutation spectrum variation among species.

The genomic footprint of whaling and isolation in fin whale populations.

Twentieth century industrial whaling pushed several species to the brink of extinction, with fin whales being the most impacted. However, a small, resident population in the Gulf of California was not targeted by whaling. Here, we analyzed 50 whole-genomes from the Eastern North Pacific (ENP) and Gulf of California (GOC) fin whale populations to investigate their demographic history and the genomic effects of natural and human-induced bottlenecks. We show that the two populations diverged ~16,000 years ago, after which the ENP population expanded and then suffered a 99% reduction in effective size during the whaling period. In contrast, the GOC population remained small and isolated, receiving less than one migrant per generation. However, this low level of migration has been crucial for maintaining its viability. Our study exposes the severity of whaling, emphasizes the importance of migration, and demonstrates the use of genome-based analyses and simulations to inform conservation strategies.

The critically endangered vaquita is not doomed to extinction by inbreeding depression.

In cases of severe wildlife population decline, a key question is whether recovery efforts will be impeded by genetic factors, such as inbreeding depression. Decades of excess mortality from gillnet fishing have driven Mexico's vaquita porpoise (Phocoena sinus) to ~10 remaining individuals. We analyzed whole-genome sequences from 20 vaquitas and integrated genomic and demographic information into stochastic, individual-based simulations to quantify the species' recovery potential. Our analysis suggests that the vaquita's historical rarity has resulted in a low burden of segregating deleterious variation, reducing the risk of inbreeding depression. Similarly, genome-informed simulations suggest that the vaquita can recover if bycatch mortality is immediately halted. This study provides hope for vaquitas and other naturally rare endangered species and highlights the utility of genomics in predicting extinction risk.

MHC DQB-1 polymorphism in the Gulf of California fin whale (Balaenoptera physalus) population.

One of the most isolated populations of fin whales occurs in the Gulf of California (GOC) with 400-800 individuals. This population shows reduced neutral genetic variation in comparison to the North Pacific population and thus might also display limited adaptive polymorphism. We sampled 36 fin whales from the GOC and assessed genetic variation at exon 2 of the major histocompatibility complex class II DQB-1 genes responsible for eliciting immune responses. Three divergent alleles were found with higher nonsynonymous than synonymous substitution rates within the peptide-binding region positions as well as the likely retention of ancient alleles, indicating that positive selection has shaped diversity in this species. Limited levels of nonneutral polymorphism, in addition to previously described low levels of neutral polymorphism, are consistent with the results of previous studies on vertebrate populations that have remained small and demographically stable for a very long time. Such low genetic variation in the GOC fin whales could be explained by 2 demographic scenarios: an ancient isolated population with limited gene flow or a more recent founder event after the last glacial maximum with very restricted gene flow.

Playing by the rules? Phenotypic adaptation to temperate environments in an American marsupial.

Phenotypic variation along environmental gradients can provide evidence suggesting local adaptation has shaped observed morphological disparities. These differences, in traits such as body and extremity size, as well as skin and coat pigmentation, may affect the overall fitness of individuals in their environments. The Virginia opossum (Didelphis virginiana) is a marsupial that shows phenotypic variation across its range, one that has recently expanded into temperate environments. It is unknown, however, whether the variation observed in the species fits adaptive ecogeographic patterns, or if phenotypic change is associated with any environmental factors. Using phenotypic measurements of over 300 museum specimens of Virginia opossum, collected throughout its distribution range, we applied regression analysis to determine if phenotypes change along a latitudinal gradient. Then, using predictors from remote-sensing databases and a random forest algorithm, we tested environmental models to find the most important variables driving the phenotypic variation. We found that despite the recent expansion into temperate environments, the phenotypic variation in the Virginia opossum follows a latitudinal gradient fitting three adaptive ecogeographic patterns codified under Bergmann's, Allen's and Gloger's rules. Temperature seasonality was an important predictor of body size variation, with larger opossums occurring at high latitudes with more seasonal environments. Annual mean temperature predicted important variation in extremity size, with smaller extremities found in northern populations. Finally, we found that precipitation and temperature seasonality as well as low temperatures were strong environmental predictors of skin and coat pigmentation variation; darker opossums are distributed at low latitudes in warmer environments with higher precipitation seasonality. These results indicate that the adaptive mechanisms underlying the variation in body size, extremity size and pigmentation are related to the resource seasonality, heat conservation, and pathogen-resistance hypotheses, respectively. Our findings suggest that marsupials may be highly susceptible to environmental changes, and in the case of the Virginia opossum, the drastic phenotypic evolution in northern populations may have arisen rapidly, facilitating the colonization of seasonal and colder habitats of temperate North America.