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Mountain gorillas are an endangered great ape subspecies and a prominent focus for conservation, yet we know little about their genomic diversity and evolutionary past. We sequenced whole genomes from multiple wild individuals and compared the genomes of all four Gorilla subspecies. We found that the two eastern subspecies have experienced a prolonged population decline over the past 100,000 years, resulting in very low genetic diversity and an increased overall burden of deleterious variation. A further recent decline in the mountain gorilla population has led to extensive inbreeding, such that individuals are typically homozygous at 34% of their sequence, leading to the purging of severely deleterious recessive mutations from the population. We discuss the causes of their decline and the consequences for their future survival.

The birth of new genes is an important motor of evolutionary innovation. Whereas many new genes arise by gene duplication, others originate at genomic regions that did not contain any genes or gene copies. Some of these newly expressed genes may acquire coding or non-coding functions and be preserved by natural selection. However, it is yet unclear which is the prevalence and underlying mechanisms of de novo gene emergence. In order to obtain a comprehensive view of this process, we have performed in-depth sequencing of the transcriptomes of four mammalian species--human, chimpanzee, macaque, and mouse--and subsequently compared the assembled transcripts and the corresponding syntenic genomic regions. This has resulted in the identification of over five thousand new multiexonic transcriptional events in human and/or chimpanzee that are not observed in the rest of species. Using comparative genomics, we show that the expression of these transcripts is associated with the gain of regulatory motifs upstream of the transcription start site (TSS) and of U1 snRNP sites downstream of the TSS. In general, these transcripts show little evidence of purifying selection, suggesting that many of them are not functional. However, we find signatures of selection in a subset of de novo genes which have evidence of protein translation. Taken together, the data support a model in which frequently-occurring new transcriptional events in the genome provide the raw material for the evolution of new proteins.

Variant transthyretin (ATTRv) amyloidosis is a rare, inherited disorder caused by mutations in the TTR gene, leading to amyloid fibril deposition. The Balearic Islands are a known endemic focus for the NP_000362.1:p.Val50Met (V30M) variant, one of the most prevalent pathogenic mutations. We analysed 23 years of genetic testing data from the Balearic Islands’ public health system to determine the prevalence and distribution of ATTR pathogenic variants, with a focus on V30M. A total of 1,478 individuals underwent genetic testing, with 319 positive tests for ATTRv: 308 carried the V30M variant (96.4%) and 11 carried other pathogenic variants. The V30M prevalence was highest in Mallorca and Menorca (1 in 2,900 and 4,700, respectively), with lower rates in Ibiza and Formentera. The co-occurrence of V30M and NP_000362.1:p.Gly26Ser (G6S) on the same chromosome in 93% of V30M carriers suggests a common origin. This study becomes the first registry of ATTRv in the Balearic Islands, aiming to raise awareness among clinicians across all areas and services while enabling more accurate diagnostics, informed genetic counselling, and targeted clinical follow-ups. We also postulate the Balearic Islands as a major global focus for the V30M variant, with a distinct genetic profile suggesting a unique founder effect within the region.

Populations of the common chimpanzee (Pan troglodytes) are in an impending risk of going extinct in the wild as a consequence of damaging anthropogenic impact on their natural habitat and illegal pet and bushmeat trade. Conservation management programmes for the chimpanzee have been established outside their natural range (ex situ), and chimpanzees from these programmes could potentially be used to supplement future conservation initiatives in the wild (in situ). However, these programmes have often suffered from inadequate information about the geographical origin and subspecies ancestry of the founders. Here, we present a newly designed capture array with ~60,000 ancestry informative markers used to infer ancestry of individual chimpanzees in ex situ populations and determine geographical origin of confiscated sanctuary individuals. From a test panel of 167 chimpanzees with unknown origins or subspecies labels, we identify 90 suitable non-admixed individuals in the European Association of Zoos and Aquaria (EAZA) Ex situ Programme (EEP). Equally important, another 46 individuals have been identified with admixed subspecies ancestries, which therefore over time, should be naturally phased out of the breeding populations. With potential for future re-introduction to the wild, we determine the geographical origin of 31 individuals that were confiscated from the illegal trade and demonstrate the promises of using non-invasive sampling in future conservation action plans. Collectively, our genomic approach provides an exemplar for ex situ management of endangered species and offers an efficient tool in future in situ efforts to combat the illegal wildlife trade.

We investigated the genetic causes of major mental disorders (MMDs) including schizophrenia, bipolar disorder I, major depressive disorder and attention deficit hyperactive disorder, in a large family pedigree from Alpujarras, South of Spain, a region with high prevalence of psychotic disorders. We applied a systematic genomic approach based on karyotyping (n = 4), genotyping by genome-wide SNP array (n = 34) and whole-genome sequencing (n = 12). We performed genome-wide linkage analysis, family-based association analysis and polygenic risk score estimates. Significant linkage was obtained at chromosome 9 (9q33.1–33.2, LOD score = 4.11), a suggestive region that contains five candidate genes ASTN2 , BRINP1 , C5 , TLR4 and TRIM32, previously associated with MMDs. Comprehensive analysis associated the MMD phenotype with genes of the immune system with dual brain functions. Moreover, the psychotic phenotype was enriched for genes involved in synapsis. These results should be considered once studying the genetics of psychiatric disorders in other families, especially the ones from the same region, since founder effects may be related to the high prevalence.

Background Whole genome re-sequencing data from dogs and wolves are now commonly used to study how natural and artificial selection have shaped the patterns of genetic diversity. Single nucleotide polymorphisms, microsatellites and variants in mitochondrial DNA have been interrogated for links to specific phenotypes or signals of domestication. However, copy number variation (CNV), despite its increasingly recognized importance as a contributor to phenotypic diversity, has not been extensively explored in canids. Results Here, we develop a new accurate probabilistic framework to create fine-scale genomic maps of segmental duplications (SDs), compare patterns of CNV across groups and investigate their role in the evolution of the domestic dog by using information from 34 canine genomes. Our analyses show that duplicated regions are enriched in genes and hence likely possess functional importance. We identify 86 loci with large CNV differences between dogs and wolves, enriched in genes responsible for sensory perception, immune response, metabolic processes, etc. In striking contrast to the observed loss of nucleotide diversity in domestic dogs following the population bottlenecks that occurred during domestication and breed creation, we find a similar proportion of CNV loci in dogs and wolves, suggesting that other dynamics are acting to particularly select for CNVs with potentially functional impacts. Conclusions This work is the first comparison of genome wide CNV patterns in domestic and wild canids using whole-genome sequencing data and our findings contribute to study the impact of novel kinds of genetic changes on the evolution of the domestic dog.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

High-coverage sequencing of 79 (wild and captive) individuals representing all six non-human great ape species has identified over 88 million single nucleotide polymorphisms providing insight into ape genetic variation and evolutionary history and enabling comparison with human genetic diversity. Genetic picture of endangered great apes In an effort to provide insights into great ape genetic variation, the authors sequence 79 wild- and captive-born individuals from across all six great ape species and seven subspecies. Their data and analyses shed light on population structure and gene flow, inbreeding, inferred dynamics of effective population sizes and the differences in the rate of gene loss among the great apes. This new catalogue of great ape genome diversity provides a valuable resource for evolutionary and conservation studies. Most great ape genetic variation remains uncharacterized 1 , 2 ; however, its study is critical for understanding population history 3 , 4 , 5 , 6 , recombination 7 , selection 8 and susceptibility to disease 9 , 10 . Here we sequence to high coverage a total of 79 wild- and captive-born individuals representing all six great ape species and seven subspecies and report 88.8 million single nucleotide polymorphisms. Our analysis provides support for genetically distinct populations within each species, signals of gene flow, and the split of common chimpanzees into two distinct groups: Nigeria–Cameroon/western and central/eastern populations. We find extensive inbreeding in almost all wild populations, with eastern gorillas being the most extreme. Inferred effective population sizes have varied radically over time in different lineages and this appears to have a profound effect on the genetic diversity at, or close to, genes in almost all species. We discover and assign 1,982 loss-of-function variants throughout the human and great ape lineages, determining that the rate of gene loss has not been different in the human branch compared to other internal branches in the great ape phylogeny. This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.

Our closest living relatives, chimpanzees and bonobos, have a complex demographic history. We analyzed the high-coverage whole genomes of 75 wild-born chimpanzees and bonobos from 10 countries in Africa. We found that chimpanzee population substructure makes genetic information a good predictor of geographic origin at country and regional scales. Multiple lines of evidence suggest that gene flow occurred from bonobos into the ancestors of central and eastern chimpanzees between 200,000 and 550,000 years ago, probably with subsequent spread into Nigeria-Cameroon chimpanzees. Together with another, possibly more recent contact (after 200,000 years ago), bonobos contributed less than 1% to the central chimpanzee genomes. Admixture thus appears to have been widespread during hominid evolution.

Cancer arises from the complex interplay of various factors. Traditionally, the identification of driver genes focuses primarily on the analysis of somatic mutations. We describe a new method for the detection of driver gene pairs based on an epistasis analysis that considers both germline and somatic variations. Specifically, the identification of significantly mutated gene pairs entails the calculation of a contingency table, wherein one of the co-mutated genes can exhibit a germline variant. By adopting this approach, it is possible to select gene pairs in which the individual genes do not exhibit significant associations with cancer. Finally, a survival analysis is used to select clinically relevant gene pairs. To test the efficacy of the new algorithm, we analyzed the colon adenocarcinoma (COAD) and lung adenocarcinoma (LUAD) samples available at The Cancer Genome Atlas (TCGA). In the analysis of the COAD and LUAD samples, we identify epistatic gene pairs significantly mutated in tumor tissue with respect to normal tissue. We believe that further analysis of the gene pairs detected by our method will unveil new biological insights, enhancing a better description of the cancer mechanism.