The analysis of genetic variation to estimate demographic and historical parameters and to quantitatively compare alternative scenarios recently gained a powerful and flexible approach: the Approximate Bayesian Computation (ABC). The likelihood functions does not need to be theoretically specified, but posterior distributions can be approximated by simulation even assuming very complex population models including both natural and human-induced processes. Prior information can be easily incorporated and the quality of the results can be analysed with rather limited additional effort. ABC is not a statistical analysis per se, but rather a statistical framework and any specific application is a sort of hybrid between a simulation and a data-analysis study. Complete software packages performing the necessary steps under a set of models and for specific genetic markers are already available, but the flexibility of the method is better exploited combining different programs. Many questions relevant in ecology can be addressed using ABC, but adequate amount of time should be dedicated to decide among alternative options and to evaluate the results. In this paper we will describe and critically comment on the different steps of an ABC analysis, analyse some of the published applications of ABC and provide user guidelines.

Our closest living relatives, chimpanzees and bonobos, have a complex demographic history. We have analyzed the high-coverage whole genomes of 75 wild-born chimpanzees and bonobos from ten countries in Africa. We find that chimpanzee population sub-structure makes genetic information a good predictor of geographic origin at country and regional scales. Most strikingly, multiple lines of evidence suggest that gene flow occurred from bonobos into the ancestors of central and eastern chimpanzees between 200 and 550 thousand years ago (Kya), probably with subsequent spread into Nigeria-Cameroon chimpanzees. Together with another possibly more recent contact (after 200 Kya), bonobos contributed less than 1% to the central chimpanzee genomes. Admixture thus appears to have been widespread during hominid evolution.

Patients with established type 2 diabetes display both β-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF7L2, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.

ORCID ID: 0000-0001-9598-3131 (R.P.)Using RNA sequencing technology and de novo transcriptome assembly, we compared representative sets of wild and domesticated accessions of common bean (Phaseolus vulgaris) from Mesoamerica. RNA was extracted at the first true-leaf stage, and de novo assembly was used to develop a reference transcriptome; the final data set consists of ;190,000 single nucleotide polymorphisms from 27,243 contigs in expressed genomic regions. A drastic reduction in nucleotide diversity (;60%) is evident for the domesticated form, compared with the wild form, and almost 50% of the contigs that are polymorphic were brought to fixation by domestication. In parallel, the effects of domestication decreased the diversity of gene expression (18%). While the coexpression networks for the wild and domesticated accessions demonstrate similar seminal network properties, they show distinct community structures that are enriched for different molecular functions. After simulating the demographic dynamics during domestication, we found that 9% of the genes were actively selected during domestication. We also show that selection induced a further reduction in the diversity of gene expression (26%) and was associated with 5-fold enrichment of differentially expressed genes. While there is substantial evidence of positive selection associated with domestication, in a few cases, this selection has increased the nucleotide diversity in the domesticated pool at target loci associated with abiotic stress responses, flowering time, and morphology.

Survival and divergence in a small group: the extraordinary genomic history of the endangered Apennine brown bear stragglers 2 AbstractAbout 100 km east of Rome, in the Central Apennine mountains, a critically endangered population of approximately fifty brown bears live in complete isolation. Mating outside this population is prevented by several hundred kilometers of bear-free territories. We exploited this natural experiment to better understand the gene and genomic consequences of surviving at extremely small population size. First, we found that brown bear populations in Europe lost connectivity since Neolithic times, when farming communities expanded and forest burning was used for land clearance. In Central Italy, this resulted in a 40-fold population decline. The overall genomic impact of this decline included the complete loss of variation in the mitochondrial genome and along long stretches of the nuclear genome. Several private and deleterious amino acid changes were fixed by random drift; predicted effects include energy deficit, muscle weakness, anomalies in cranial and skeletal development, and reduced aggressiveness. Despite this extreme loss of diversity, Apennine bear genomes show non-random peaks of high variation, possibly maintained by balancing selection, at genomic regions significantly enriched for genes associated with immune and olfactory systems. Challenging the paradigm of increased extinction risk in small populations, we suggest that random fixation of deleterious alleles a) can be an important driver of divergence in isolation, b) can be tolerated when balancing selection prevents random loss of variation at important genes and c) is followed by or results directly in favorable behavioral changes. SignificanceA small and relict population of brown bears lives in complete isolation in the Italian Apennine mountains, providing a unique opportunity to study the impact of drift and selection on the genomes of a large endangered mammal and to reconstruct the phenotypic consequences and the conservation implications of such evolutionary processes. The Apennine bear is highly inbred and harbors very low genomic variation. Several deleterious mutations have been accumulated by drift. We found evidence that this is a consequence of habitat fragmentation in the Neolithic, when human expansion and land clearance shrank its habitat, and that retention of variation at immune system and olfactory receptor genes, as well as changes in diet and behavior, prevented the extinction of the Apennine bear.