The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human specific. This study will open a wide range of research avenues for future primate genomic research.

Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.

Large mammalian herbivores (megafauna) have experienced extinctions and declines since prehistory. Introduced megafauna have partly counteracted these losses yet are thought to have unusually negative effects on plants compared with native megafauna. Using a meta-analysis of 3995 plot-scale plant abundance and diversity responses from 221 studies, we found no evidence that megafauna impacts were shaped by nativeness, “invasiveness,” “feralness,” coevolutionary history, or functional and phylogenetic novelty. Nor was there evidence that introduced megafauna facilitate introduced plants more than native megafauna. Instead, we found strong evidence that functional traits shaped megafauna impacts, with larger-bodied and bulk-feeding megafauna promoting plant diversity. Our work suggests that trait-based ecology provides better insight into interactions between megafauna and plants than do concepts of nativeness.

Across the last ~50,000 years (the late Quaternary) terrestrial vertebrate faunas have experienced severe losses of large species (megafauna), with most extinctions occurring in the Late Pleistocene and Early to Middle Holocene. Debate on the causes has been ongoing for over 200 years, intensifying from the 1960s onward. Here, we outline criteria that any causal hypothesis needs to account for. Importantly, this extinction event is unique relative to other Cenozoic (the last 66 million years) extinctions in its strong size bias. For example, only 11 out of 57 species of megaherbivores (body mass ≥1,000 kg) survived to the present. In addition to mammalian megafauna, certain other groups also experienced substantial extinctions, mainly large non-mammalian vertebrates and smaller but megafauna-associated taxa. Further, extinction severity and dates varied among continents, but severely affected all biomes, from the Arctic to the tropics. We synthesise the evidence for and against climatic or modern human (Homo sapiens) causation, the only existing tenable hypotheses. Our review shows that there is little support for any major influence of climate, neither in global extinction patterns nor in fine-scale spatiotemporal and mechanistic evidence. Conversely, there is strong and increasing support for human pressures as the key driver of these extinctions, with emerging evidence for an initial onset linked to pre-sapienshominins prior to the Late Pleistocene. Subsequently, we synthesize the evidence for ecosystem consequences of megafauna extinctions and discuss the implications for conservation and restoration. A broad range of evidence indicates that the megafauna extinctions have elicited profound changes to ecosystem structure and functioning. The late-Quaternary megafauna extinctions thereby represent an early, large-scale human-driven environmental transformation, constituting a progenitor of the Anthropocene, where humans are now a major player in planetary functioning. Finally, we conclude that megafauna restoration via trophic rewilding can be expected to have positive effects on biodiversity across varied Anthropocene settings.

Noncoding DNA is central to our understanding of human gene regulation and complex diseases^1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome^3–9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA¹⁰, the relatively short timescales separating primate species¹¹, and the previously limited availability of whole-genome sequences¹². Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.

The worldwide extinction of megafauna during the Late Pleistocene and Early Holocene is evident from the fossil record, with dominant theories suggesting a climate, human or combined impact cause. Consequently, two disparate scenarios are possible for the surviving megafauna during this time period - they could have declined due to similar pressures, or increased in population size due to reductions in competition or other biotic pressures. We therefore infer population histories of 139 extant megafauna species using genomic data which reveal population declines in 91% of species throughout the Quaternary period, with larger species experiencing the strongest decreases. Declines become ubiquitous 32–76 kya across all landmasses, a pattern better explained by worldwide Homo sapiens expansion than by changes in climate. We estimate that, in consequence, total megafauna abundance, biomass, and energy turnover decreased by 92–95% over the past 50,000 years, implying major human-driven ecosystem restructuring at a global scale.