Eli Geffen

Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication

Advances in genome technology have facilitated a new understanding of the historical and genetic processes crucial to rapid phenotypic evolution under domestication. To understand the process of dog diversification better, we conducted an extensive genome-wide survey of more than 48,000 single nucleotide polymorphisms in dogs and their wild progenitor, the grey wolf. Here we show that dog breeds share a higher proportion of multi-locus haplotypes unique to grey wolves from the Middle East, indicating that they are a dominant source of genetic diversity for dogs rather than wolves from east Asia, as suggested by mitochondrial DNA sequence data. Furthermore, we find a surprising correspondence between genetic and phenotypic/functional breed groupings but there are exceptions that suggest phenotypic diversification depended in part on the repeated crossing of individuals with novel phenotypes. Our results show that Middle Eastern wolves were a critical source of genome diversity, although interbreeding with local wolf populations clearly occurred elsewhere in the early history of specific lineages. More recently, the evolution of modern dog breeds seems to have been an iterative process that drew on a limited genetic toolkit to create remarkable phenotypic diversity.

Genome Sequencing Highlights the Dynamic Early History of Dogs

To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we generated high-quality genome sequences from three gray wolves, one from each of the three putative centers of dog domestication, two basal dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. Analysis of these sequences supports a demographic model in which dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow. In dogs, the domestication bottleneck involved at least a 16-fold reduction in population size, a much more severe bottleneck than estimated previously. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was substantially larger than represented by modern wolf populations. We narrow the plausible range for the date of initial dog domestication to an interval spanning 11–16 thousand years ago, predating the rise of agriculture. In light of this finding, we expand upon previous work regarding the increase in copy number of the amylase gene (AMY2B) in dogs, which is believed to have aided digestion of starch in agricultural refuse. We find standing variation for amylase copy number variation in wolves and little or no copy number increase in the Dingo and Husky lineages. In conjunction with the estimated timing of dog origins, these results provide additional support to archaeological finds, suggesting the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that, surprisingly, none of the extant wolf lineages from putative domestication centers is more closely related to dogs, and, instead, the sampled wolves form a sister monophyletic clade. This result, in combination with dog-wolf admixture during the process of domestication, suggests that a re-evaluation of past hypotheses regarding dog origins is necessary.

A genome-wide perspective on the evolutionary history of enigmatic wolf-like canids

High-throughput genotyping technologies developed for model species can potentially increase the resolution of demographic history and ancestry in wild relatives. We use a SNP genotyping microarray developed for the domestic dog to assay variation in over 48K loci in wolf-like species worldwide. Despite the high mobility of these large carnivores, we find distinct hierarchical population units within gray wolves and coyotes that correspond with geographic and ecologic differences among populations. Further, we test controversial theories about the ancestry of the Great Lakes wolf and red wolf using an analysis of haplotype blocks across all 38 canid autosomes. We find that these enigmatic canids are highly admixed varieties derived from gray wolves and coyotes, respectively. This divergent genomic history suggests that they do not have a shared recent ancestry as proposed by previous researchers. Interspecific hybridization, as well as the process of evolutionary divergence, may be responsible for the observed phenotypic distinction of both forms. Such admixture complicates decisions regarding endangered species restoration and protection.

Climate and habitat barriers to dispersal in the highly mobile grey wolf

We reanalysed published data to evaluate whether climate and habitat are barriers to dispersal in one of the most mobile and widely distributed mammals, the grey wolf (Canis lupus). Distance‐based redundancy analysis (dbRDA) was used to examine the amount of variation in genetic distances that could be explained by an array of environmental factors, including geographical distance. Patterns in genetic variation were also examined using MDS plots among populations and relationships between genetic structure and individual environmental variables were further explored using the BIOENV procedure. We found that, contrary to a previous report, a pattern of isolation with distance is evident on a continental scale in the North American wolf population. This pattern is apparently related to climate and habitat. Specifically, vegetation types appear to play a role in the genetic dissimilarities among populations. When we controlled for the effect of spatial variation, climate was still associated with genetic distance. Further, partitioning of geographical distances into latitudinal and longitudinal axes revealed that the east–west gradient had the strongest relationship with genetic distance. We suggest two possible mechanisms by which environmental conditions may influence the dispersal decisions made by wolves.

The Frequent 5,10-Methylenetetrahydrofolate Reductase C677T Polymorphism Is Associated with a Common Haplotype in Whites, Japanese, and Africans

The common 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism causes decreased activity of this enzyme and can be associated with mild-to-moderate hyperhomocysteinemia in homozygotes, particularly when there is folic acid deficiency, as well as with vascular dementia, arterial thrombosis, venous thrombosis, neural-tube defects, and fetal loss. When folic acid intake is sufficient, homozygotes for MTHFR 677T appear to be protected against colon cancer and acute lymphatic leukemia, and fetuses bearing this genotype have an augmented survival. The distribution of MTHFR 677T is worldwide, but its frequency in different populations varies extensively. In the present study, we addressed the question of whether the MTHFR 677T alteration has an ancestral origin or has occurred repeatedly. We analyzed the frequency distribution of the previously described polymorphism A1298C in exon 7 and of three intronic dimorphisms, in white Israelis (Jews and Arabs), Japanese, and Ghanaian Africans. The 677T allele was, remarkably, associated with one haplotype, G-T-A-C, in white and Japanese homozygotes. Among the Africans, analysis of maximum likelihood also disclosed an association with the G-T-A-C haplotype, although none of the 174 subjects examined was homozygous for MTHFR 677T. These results suggest that the MTHFR 677T alteration occurred on a founder haplotype that may have had a selective advantage.

A molecular genetic analysis of social structure, dispersal, and interpack relationships of the African wild dog (Lycaon pictus )

Abstract The African wild dog is a highly social, pack-living predator of the African woodland and savannah. The archetypal wild dog pack consists of a single dominant breeding pair, their offspring, and non-breeding adults who are either offspring or siblings of one of the breeding pair. Non-breeding adults cooperate in hunting, provisioning and the protection of young. From these observations follows the prediction that the genetic structure of wild dogs packs should resemble that of a multigenerational family, with all same-sexed adults and offspring within a pack related as sibs or half-sibs. Additionally, a higher kinship between females from neighboring packs should be evident if females tend to have small dispersal distances relative to males. We test these predictions through analysis of mitochondrial DNA control region sequences and 14 microsatellite loci in nine wild dog packs from Kruger National Park, Republic of South Africa. We show that as predicted, African wild dog packs generally consist of an unrelated alpha male and female, subdominant close relatives, and offspring of the breeding pair. Sub-dominant wild dogs occasionally reproduce but their offspring rarely survive to 1 year of age. Relatedness influences the timing and location of dispersal events as dispersal events frequently coincide with a change in pack dominance hierarchy and dispersers often move to areas with a high proportion of close relatives.

Genetic diversity and population structure of Tasmanian devils, the largest marsupial carnivore

Genetic diversity and population structure were investigated across the core range of Tasmanian devils (Sarcophilus laniarius; Dasyuridae), a wide‐ranging marsupial carnivore restricted to the island of Tasmania. Heterozygosity (0.386–0.467) and allelic diversity (2.7–3.3) were low in all subpopulations and allelic size ranges were small and almost continuous, consistent with a founder effect. Island effects and repeated periods of low population density may also have contributed to the low variation. Within continuous habitat, gene flow appears extensive up to 50 km (high assignment rates to source or close neighbour populations; nonsignificant values of pairwise FST), in agreement with movement data. At larger scales (150–250 km), gene flow is reduced (significant pairwise FST) but there is no evidence for isolation by distance. The most substantial genetic structuring was observed for comparisons spanning unsuitable habitat, implying limited dispersal of devils between the well‐connected, eastern populations and a smaller northwestern population. The genetic distinctiveness of the northwestern population was reflected in all analyses: unique alleles; multivariate analyses of gene frequency (multidimensional scaling, minimum spanning tree, nearest neighbour); high self‐assignment (95%); two distinct populations for Tasmania were detected in isolation by distance and in Bayesian model‐based clustering analyses. Marsupial carnivores appear to have stronger population subdivisions than their placental counterparts.

Size, Life-History Traits, and Social Organization in the Canidae: A Reevaluation

Any selective advantages of large body size may be counteracted by an increase in energetic costs associated with reproduction. In canids, larger female body size has been sug- gested to be associated with increasingly altricial young, larger litter sizes, and an increase in female pre- and postpartum energetic investment in offspring. It is hypothesized that the chang- ing costs of reproduction with increasing body size result in a size-related diversity of canid reproductive life histories and social organization. Smaller canid species require less postpartum investment and thus tend toward polygyny and have a skewed dispersal ratio toward males. Larger species, with greater prepartum investment, require greater male investment in the rear- ing of offspring and thus tend to be group living. Using data on canid life histories, a phylogeny of the Canidae based on 383 base pairs of mitochondrial DNA, and an autoregressive compara- tive method, we found this hypothesis was not supported. Strong isometric relationships be- tween neonate weight and female weight indicate that neonate size is constrained by female size directly or by parameters co-varying with female body size. Female weight accounted for only 26% of the variance in litter size, and no correlation was found between litter size and neonate weight. This result implies that female prenatal investment can be adjusted only by litter size (and not by neonate or litter weight), which in turn may be adjusted according to resource availability, an explanation supported by field and laboratory studies. In general, we hypothesize that much of canid interspecific and intraspecific variation in social structure may be explained by focusing on proximate enivironmental mechanisms, specifically resource avail- ability.

A novel method using hair for determining hormonal levels in wildlife

ormones influence behaviour, and are also influ-enced by behaviour. Monitoring their levels cantherefore provide insights into the mechanistic aspects ofbehaviour. In male mammals for example, elevated levelsof testosterone are associated with increased aggressionand dominance (Creel et al. 1993, 1997; Mazur & Booth1998) and in social mammals, levels of stress hormones(e.g. corticosterone, glucocorticoid and cortisol) areassociated with rank (Sapolsky 1985; Creel et al. 1996,1997). Research has associated hormone levels with dif-ferent behaviours such as sexual, reproductive, courtship,parental, aggressive and feeding behaviours. Comparativetools for hormonal analysis provide insights into evolu-tionary theories based on behavioural aspects, such asreproductive suppression and the ‘challenge hypothesis’(e.g. Creel et al. 1993).In field studies, hormones are usually extracted fromblood samples, or noninvasively from saliva, urine andfaeces (Creel et al. 1992; Cavigelli 1999; Hirschenhauseret al. 1999; von Engelhardt et al. 2000). Samples derivedfrom trapped or handled animals are problematicalbecause stress may alter blood and urine hormonal levels(Creel et al. 1992). Additional problems with bloodsamples are that they are not always available, theamount that can be taken at a given time is limited, andvarious safety and ethical issues exist. Furthermore, bloodand saliva must be transported cold or frozen, conditionsthat are sometimes difficult to obtain in the field (Yang etal. 1998). Urine and faeces samples are sometimes diffi-cult to obtain from free-ranging animals that cannot becontinuously observed, or from species that deposit incommon latrines.An alternative source for hormones may be found inhair, which can be collected noninvasively, and is alreadyused to extract DNA (Woodruff 1993; Morin et al. 1994),trace metals, naturally occurring compounds and drugs(Wheeler et al. 1998). Hair is safe, readily available, andeasy to store and transport. Hair sampling does notinvolve pain or possible infection, and the analysis isunaffected by the momentary stress of capture (Yang et al.1998). Hair analysis may allow one to monitor hormonalchanges over weeks or months (between moults; Maurelet al. 1986) by shaving off a patch of hair and resamplingthe newly grown hair. Hormonal hair analysis offersonly a long-term profile, however, and is not suitable formonitoring hourly or daily (short-term) fluctuations inhormonal levels. It provides the resolution needed forstudies of main behavioural trends, especially in stablehierarchical social systems. Hair has already been used todiagnose early pregnancy in cows by detection of proges-terone (Liu et al. 1988), to detect oestradiol and testoster-one in cattle (Gleixner & Meyer 1997) and anabolicsteroid and corticosteroid abuse in athletes (Bowers S Hold et al. 1999; Kintz et al. 1999; Cirimeleet al. 2000). In humans, the levels of steroid hormones inhair do not vary significantly between different regions ofthe scalp (Wheeler et al. 1998). Oestradiol, progesteroneand testosterone levels measured in healthy humanadults’ hair correlate significantly with the levelsmeasured in their serum (Yang et al. 1998).As an example of the utility of this method, we usedata from our long-term study on rock hyrax,

Geographic variation in body size: the effects of ambient temperature and precipitation

Latitudinal trends in body size have been explained as a response to temperature- or water-related factors, which are predictors of primary production. We used the first principal component calculated from three body parameters (weight, body length and the greatest length of the skull) of a sample of mammals from Israel and Sinai to determine those species that vary in size geographically, and whether such variation is related to annual rainfall, average minimum January temperature and average maximum August temperature. We used a conservative approach to discern the effects of precipitation and temperature by applying sequential regression. Variable priorities were assigned according to their bivariate correlation with body size, except for rainfall and its interactions that entered into the model last. Eleven species (Acomys cahirinus, Apodemus mystacinus, Canis lupus, Crocidura suaveolens, Gerbillus dasyurus, Hyaena hyaena, Lepus capensis, Meles meles, Meriones tristrami, Rousettus aegyptius and Vulpes vulpes) of the 17 species examined varied in size geographically. In five of them, rainfall was positively related to body size, while in one species it was negatively related to it. Contrary to the prediction of Bergmann’s rule, mean minimum January temperature was positively related to body size in five species and negatively related to body size in two species (C. suaveolens and G. dasyurus). As predicted by Bergmann’s rule, maximum June temperature was negatively related to body size in three species, and positively so in one (L. capensis). Primary production, particularly in desert and semi-desert areas, is determined mainly by precipitation. The above results indicate that, in our sample, primary production has an important effect on body size of several species of mammals. This is evident from the considerable proportion of the variability in body size explained by rain. However, low ambient temperatures may slow down and even inhibit photosynthesis. Hence, the observed positive relationships between average minimum January temperature and body size in four of the six species influenced by rain further support this conclusion.