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Current advances in primate genomics: novel approaches for understanding evolution and disease

Abstract

Primate genomics holds the key to understanding fundamental aspects of human evolution and disease. However, genetic diversity and functional genomics data sets are currently available for only a few of the more than 500 extant primate species. Concerted efforts are under way to characterize primate genomes, genetic polymorphism and divergence, and functional landscapes across the primate phylogeny. The resulting data sets will enable the connection of genotypes to phenotypes and provide new insight into aspects of the genetics of primate traits, including human diseases. In this Review, we describe the existing genome assemblies as well as genetic variation and functional genomic data sets. We highlight some of the challenges with sample acquisition. Finally, we explore how technological advances in single-cell functional genomics and induced pluripotent stem cell-derived organoids will facilitate our understanding of the molecular foundations of primate biology.

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Fig. 1: Genomic data sets in primates are concentrated in a few species used as experimental models while they remain sparse across the rest of species and clades.
Fig. 2: Omic studies conducted on tissues and organs derived from iPSCs in primates.
Fig. 3: A roadmap for integrative comparative studies.

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Acknowledgements

The authors thank William R. Bradley for help collecting metadata and all the authors with important contributions to primate comparative omics, many of which could not be included in this Review. T.M.-B. is supported by funding from the European Research Council (ERC) under the European Union Horizon 2020 Research and Innovation Programme (grant agreement No. 864203), PID2021-126004NB-100 (MINECO/FEDER, UE), “Unidad de Excelencia María de Maeztu”, funded by the AEI (CEX2018-000792-M), US National Institutes of Health (NIH) 1R01HG010898-01A1, and Secretaria d’Universitats i Recerca and CERCA Programme del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880). G.S. is supported by grant MS20/00064 from Instituto de Salud Carlos III (Spain) and the European Social Fund, and grant PID2019-104700GA-I00 funded by the AEI, Spain. G.S. is also supported by the NIH grant R01HG010898-01. J.L.K. is supported by National Science Foundation IOS 1931650 and María de Maeztu Mobility Fellowship.

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Supplementary information

Glossary

Allotetraploid

Composite cell lines from different diploid species.

Assembloids

Assemblies of organoids derived from different cell lineages.

Balancing selection

The set of selective processes that maintain genetic variation longer than expected from genetic drift.

Cellular primatology

Comparative studies focused on the cellular process underpinning the phenotypic variation among humans and non-human primates, including cell development, molecular features, tissue composition and organization.

Composite cell lines

Cell lines obtained from the fusion of two diploid cell lines from the same or different species.

Copy number variants

(CNVs). Variable regions in the genome in which sections of the genome are repeated; the number of repeats differs between individuals.

CRISPR–Cas9

A widely used genome-editing technique consisting of a nuclease linked to a guide RNA cutting specific sites, which can be then repaired by homology-directed repair introducing the desired mutations.

Deep learning

A type of machine learning that achieves great power to predict the output concepts or classes associated with the input cases. It works by learning a representation of many nested concepts connecting the input data to the desired outputs from the exposition to multiple cases.

Epigenomic

Pertains to chemical modifications on DNA (for example, CpG-methylation) and histones (for example, methylation and acetylation) that correlate with functional features of the genome (for example, promoters, enhancers and gene transcription).

Expression quantitative trait locus

(eQTL). Site in the genome where genetic variation is associated with altered gene expression.

Genome-wide association studies

(GWAS). Studies designed to interrogate the contribution of millions of common variants to a trait or disease of interest.

Gyrification

The process of the formation of the cortical folds during brain development.

Induced pluripotent stem cells

(iPSCs). Pluripotent stem cells that are reprogrammed from somatic cells by inducing the expression of pluripotency factors.

Long-read sequencing

A group of sequencing techniques that generate sequences of thousands to millions of nucleotides. They are especially suitable for resolving structural variants and repetitive sequences.

Organoids

In vitro self-organizing 3D cell cultures resembling real organs in several aspects of structure, composition, development and function.

Pangenome reference

A representation of the genome that captures the full genomic diversity for a given species.

Reference genomes

Representative genome assemblies for given species, usually presented in haploid form, that facilitate the interpretation and analysis of resequenced data for organisms of the same or closely related species.

Topologically associating domains

Regions of the genome with a high probability of self-interaction through the formation of chromatin loops.

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Juan, D., Santpere, G., Kelley, J.L. et al. Current advances in primate genomics: novel approaches for understanding evolution and disease. Nat Rev Genet (2023). https://doi.org/10.1038/s41576-022-00554-w

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