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Genetic admixture is central to primate evolution. We combined 50 years of field observations of immigration and group demography with genomic data from ~9 generations of hybrid baboons to investigate the consequences of admixture in the wild. Despite no obvious fitness costs to hybrids, we found signatures of selection against admixture similar to those described for archaic hominins. These patterns were concentrated near genes where ancestry is strongly associated with gene expression. Our analyses also show that introgression is partially predictable across the genome. This study demonstrates the value of integrating genomic and field data for revealing how "genomic signatures of selection" (e.g., reduced introgression in low-recombination regions) manifest in nature; moreover, it underscores the importance of other primates as living models for human evolution.

AbstractAdmixture has profoundly influenced evolution across the tree of life, including in humans and other primates1,2. However, we have limited insight into the genetic and phenotypic consequences of admixture in primates, especially during its key early stages. Here, we address this gap by combining 50 years of field observations with population and functional genomic data from yellow (Papio cynocephalus) and anubis (P. anubis) baboons in Kenya, in a longitudinally studied population that has experienced both historical and recent admixture3. We use whole-genome sequencing to characterize the extent of the hybrid zone, estimate local ancestry for 442 known individuals, and predict the landscape of introgression across the genome. Despite no major fitness costs to hybrids, we identify signatures of selection against introgression that are strikingly similar to those described for archaic hominins4–6. These signatures are strongest near loci with large ancestry effects on gene expression, supporting the importance of gene regulation in primate evolution and the idea that selection targeted large regulatory effects following archaic hominin admixture7,8. Our results show that genomic data and field observations of hybrids are important and mutually informative. They therefore demonstrate the value of other primates as living models for phenomena that we cannot observe in our own lineage.

The forkhead domain FOXP2 and FOXP1 transcription factors are implicated in several cognitive disorders with language deficits, notably autism, and thus play a central role in learned vocal motor behavior in humans. Although a similar role for FoxP2 and FoxP1 is proposed for other vertebrate species, including songbirds, the neurodevelopmental expression of these genes are unknown in a species with lifelong vocal learning abilities. Like humans, budgerigars (Melopsittacus undulatus) learn new vocalizations throughout their entire lifetime. Like songbirds, budgerigars have distinct brain nuclei for vocal learning, which include the magnocellular nucleus of the medial striatum (MMSt), a basal ganglia region that is considered developmentally and functionally analogous to Area X in songbirds. Here, we used in situ hybridization and immunohistochemistry to investigate FoxP2 and FoxP1 expression in the MMSt of juvenile and adult budgerigars. We found FoxP2 mRNA and protein expression levels in the MMSt that were lower than the surrounding striatum throughout development and adulthood. In contrast, FoxP1 mRNA and protein had an elevated MMSt/striatum expression ratio as birds matured, regardless of their sex. These results show that life-long vocal plasticity in budgerigars is associated with persistent low-level FoxP2 expression in the budgerigar MMSt, and suggests the possibility that FoxP1 plays an organizational role in the neurodevelopment of vocal motor circuitry. Thus, developmental regulation of the FoxP2 and FoxP1 genes in the basal ganglia appears essential for vocal mimicry in a range of species that possess this relatively rare trait.

The early life environment can profoundly shape the trajectory of an animal's life, even years or decades later. One mechanism proposed to contribute to these early life effects is DNA methylation. However, the frequency and functional importance of DNA methylation in shaping early life effects on adult outcomes is poorly understood, especially in natural populations. Here, we integrate prospectively collected data on fitness-associated variation in the early environment with DNA methylation estimates at 477,270 CpG sites in 256 wild baboons. We find highly heterogeneous relationships between the early life environment and DNA methylation in adulthood: aspects of the environment linked to resource limitation (e.g., low-quality habitat, early life drought) are associated with many more CpG sites than other types of environmental stressors (e.g., low maternal social status). Sites associated with early resource limitation are enriched in gene bodies and putative enhancers, suggesting they are functionally relevant. Indeed, by deploying a baboon-specific, massively parallel reporter assay, we show that a subset of windows containing these sites are capable of regulatory activity, and that, for 88% of early drought-associated sites in these regulatory windows, enhancer activity is DNA methylation-dependent. Together, our results support the idea that DNA methylation patterns contain a persistent signature of the early life environment. However, they also indicate that not all environmental exposures leave an equivalent mark and suggest that socioenvironmental variation at the time of sampling is more likely to be functionally important. Thus, multiple mechanisms must converge to explain early life effects on fitness-related traits.

Capture-based enrichment techniques have revolutionized genomic analysis of species and populations for which only low-quality or contaminated DNA samples (e.g., ancient DNA, noninvasively collected DNA, environmental DNA) are available. This chapter outlines an optimized laboratory protocol for generating RNA "baits" for genome-wide capture of target DNA from a larger pool of DNA. This method relies on the in vitro transcription of biotinylated RNA baits, which has the dual benefit of eliminating the high cost of synthesizing custom baits and producing a bait set that targets the majority of regions genome-wide. We provide a detailed protocol for the three main steps involved in bait library construction: (1) making a DNA library from a high-quality DNA sample for the organism of interest or a closely related species; (2) using duplex-specific nuclease digestion to reduce the representation of repetitive regions in the DNA library; and (3) performing in vitro transcription of the repetitive region-depleted DNA library to generate biotinylated RNA baits. Where applicable, we include notes and recommendations based on our own experiences.