Primate Genomes Research Articles

Retrotrans-genomics identifies aberrant THE1B endogenous retrovirus fusion transcripts in the pathogenesis of sarcoidosis

Transposon-like human element 1B (THE1B) originates from ancient retroviral sequences integrated into the primate genome approximately 50 million years ago, now accounting for at least 27,233 copies in the human genome, suggesting their extensive influence on human genomic architecture. Here we report identification of 19 THE1B fusion transcripts through short- and long-read RNA-seq analysis, 15 of which are previously unmapped, showing elevated expression in 16 individuals with sarcoid myopathy (SM), as compared to 400 controls with various other muscle diseases. Analysis of publicly available RNA-seq data indicated a correlation between the reduced expression of eight THE1B fusion transcripts and clinical improvement in individuals with cutaneous sarcoidosis receiving tofacitinib treatment. Single-cell or single-nucleus RNA-seq analyses of sarcoidosis not only confirmed these transcripts but also revealed a novel read-through transcript, SIRPB1-SIRPD, and TREM2.1, predominantly in granuloma-associated macrophages. The expression profiles of THE1B fusion transcripts in tuberculosis (TB) significantly differed from SM in single-cell RNA-seq data, suggesting that the differences between TB’s caseous granulomas and sarcoidosis’s non-caseous granulomas might be linked to disparate expression patterns of THE1B fusion transcripts. Our retrotrans-genomics approach has not only identified the genomic landscape of sarcoidosis but also provided new insights into its etiology.

GenomeDecoder: Inferring Segmental Duplica-tions in Highly-Repetitive Genomic Regions.

The emergence of the "telomere-to-telomere" genomics brought the challenge of identifying segmental duplications (SDs) in complete genomes. It further opened a possibility for identifying the differences in SDs across individual human genomes and studying the SD evolution. These newly emerged challenges require algorithms for reconstructing SDs in the most complex genomic regions that evaded all previous attempts to analyze their architecture, such as rapidly-evolving immunoglobulin loci. We describe the GenomeDecoder algorithm for inferring SDs and apply it to analyzing genomic architectures of various loci in primate genomes. Our analysis revealed that multiple duplications/deletions led to a rapid birth/death of immunoglobulin genes within the human population and large changes in genomic architecture of immunoglobulin loci across primate genomes. Comparison of immunoglobulin loci across primate genomes suggests that they are subjected to diversifying selection. GenomeDecoder is available at https://github.com/ZhangZhenmiao/GenomeDecoder. The software version and test data used in this paper is uploaded to https://doi.org/10.5281/zenodo.14753844. Supplementary data are available at Bioinformatics online.

Evolutionary constrained genes associated with autism spectrum disorder across 2,054 nonhuman primate genomes

BackgroundSignificant progress has been made in elucidating the genetic underpinnings of Autism Spectrum Disorder (ASD). However, there are still significant gaps in our understanding of the link between genomics, neurobiology and clinical phenotype in scientific discovery. New models are therefore needed to address these gaps. Rhesus macaques (Macaca mulatta) have been extensively used for preclinical neurobiological research because of remarkable similarities to humans across biology and behaviour that cannot be captured by other experimental animals.MethodsWe used the macaque Genotype and Phenotype (mGAP) resource consisting of 2,054 macaque genomes to examine patterns of evolutionary constraint in known human neurodevelopmental genes. Residual variation intolerance scores (RVIS) were calculated for all annotated autosomal genes (N = 18,168) and Gene Set Enrichment Analysis (GSEA) was used to examine patterns of constraint across ASD genes and related neurodevelopmental genes.ResultsWe demonstrated that patterns of constraint across autosomal genes are correlated in humans and macaques, and that ASD-associated genes exhibit significant constraint in macaques (p = 9.4 × 10− 27). Among macaques, many key ASD-implicated genes were observed to harbour predicted damaging mutations. A small number of key ASD-implicated genes that are highly intolerant to mutation in humans, however, showed no evidence of similar intolerance in macaques (CACNA1D, MBD5, AUTS2 and NRXN1). Constraint was also observed across genes associated with intellectual disability (p = 1.1 × 10− 46), epilepsy (p = 2.1 × 10− 33) and schizophrenia (p = 4.2 × 10− 45), and for an overlapping neurodevelopmental gene set (p = 4.0 × 10− 10).LimitationsThe lack of behavioural phenotypes among the macaques whose genotypes were studied means that we are unable to further investigate whether genetic variants have similar phenotypic consequences among nonhuman primates.ConclusionThe presence of pathological mutations in ASD genes among macaques, along with evidence of similar genetic constraints to those in humans, provides a strong rationale for further investigation of genotype-phenotype relationships in macaques. This highlights the importance of developing primate models of ASD to elucidate the neurobiological underpinnings and advance approaches for precision medicine and therapeutic interventions.

De Novo Genome Assembly for an Endangered Lemur Using Portable Nanopore Sequencing in Rural Madagascar.

As one of the most threatened mammalian taxa, lemurs of Madagascar are facing unprecedented anthropogenic pressures. To address conservation imperatives such as this, researchers have increasingly relied on conservation genomics to identify populations of particular concern. However, many of these genomic approaches necessitate high-quality genomes. While the advent of next-generation sequencing technologies and the resulting reduction in associated costs have led to the proliferation of genomic data and high-quality reference genomes, global discrepancies in genomic sequencing capabilities often result in biological samples from biodiverse host countries being exported to facilities in the Global North, creating inequalities in access and training within genomic research. Here, we present the first published reference genome for the endangered red-fronted brown lemur (Eulemur rufifrons) from sequencing efforts conducted entirely within the host country using portable Oxford Nanopore sequencing. Using an archived E. rufifrons specimen, we conducted long-read, nanopore sequencing at the Centre ValBio Research Station near Ranomafana National Park, in rural Madagascar, generating over 750 Gb of sequencing data from 10 MinION flow cells. Exclusively using this long-read data, we assembled 2.157 gigabase, 2980-contig nuclear assembly with an N50 of 101.6 Mb and a 17,108 bp mitogenome. The nuclear assembly had 30× average coverage and was comparable in completeness to other primate reference genomes, with a 96.1% BUSCO completeness score for primate-specific genes. As the first published reference genome for E. rufifrons and the only annotated genome available for the speciose Eulemur genus, this resource will prove vital for conservation genomic studies while our efforts exhibit the potential of this protocol to address research inequalities and build genomic capacity.

Genetic Insights into Facial Variation and Craniofacial Development: Unraveling the Interplay of Genes, Expression Patterns, and Evolutionary Significance.

The development of genome technology has opened new possibilities for comparative primate genomics. Non-human primates share approximately 98% genome similarity and provides vital information into the genetic similarities and variances among species utilized as disease models. DNA study links unique genetic variations to common facial attributes such as nose and eyes. This is because of higher adaptation and improved cognitive skills over these sensual areas. Non-protein coding sequences represent approximately 85% of the human DNA under evolutionary restrictions, and the primary part of this is the cis regulatory regions. In this study, a total of 103 tissue specific human enhancers were finalized with help of VISTA Enhancer Browser that showed distinctive expression in the facial tissues and their orthologs were collected. A total of 43 out of 190 transcription factors from TRANSFAC were seen as binding in both Human and Non-Human primate enhancers. It was observed that factor binding sites of 7 of the 43 transcription factors were exclusively gained in the human eye and nose enhancers (Oct, Pax, Sox, MyoD, Foxd3, cRel and Gata). Furthermore, we performed molecular docking through PyMol; DNA & Protein (pdb) structures were modelled by SCFBio & SWISSMODEL respectively to observe interactions of the transcription factors, either by placing the contact surface of the protein exclusively to identify the DNA, to enable a representation to gain information about identification and genetic expression.

Neuroblastoma Breakpoint Family 3mer Higher Order Repeats/Olduvai Triplet Pattern in the Complete Genome of Human and Nonhuman Primates and Relation to Cognitive Capacity.

The ~1.6 kb NBPF repeat units in neuroblastoma breakpoint family (NBPF) genes are specific to humans and are associated with cognitive capacity in higher primates. While the number of NBPF monomers/Olduvai sequences in humans is approximately 2-3 times greater than in great apes, the difference in copy number values of canonical NBPF 3mer Higher-order repeats (HORs)/Olduvai triplets between humans and great apes is substantially larger. This study aims to analyze the organization and evolutionary significance of NBPF 3mer HORs/Olduvai triplets in fully sequenced primate genomes. We applied the global repeat map (GRM) algorithm to identify canonical and variant NBPF 3mer HORs/Olduvai triplets in the complete genomes of humans, chimpanzees, gorillas, and orangutans. The resulting monomer arrays were analyzed using the GRMhor algorithm to generate detailed schematic representations of NBPF HOR organization. The analysis reveals a distinct difference in NBPF-related patterns among these primates, particularly in the number of tandemly organized canonical 3mer HORs/Olduvai triplets: 61 tandemly organized canonical NBPF 3mer HORs/Olduvai triplets in humans, compared to 0 in chimpanzees and orangutans, and 9 in gorillas. When considering only tandemly organized 3mer HORs/Olduvai triplets with more than three copies, the numbers adjust to 36 in humans and 0 in great apes. Furthermore, the divergence between individual NBPF monomers in humans and great apes is twice as high as that observed within great apes. These findings support the hypothesis that the tandem organization of NBPF 3mer HORs/Olduvai triplets plays a crucial role in enhancing cognitive capacity in humans compared to great apes, potentially providing a significant evolutionary advantage. This effect complements the impact of the increased number of individual NBPF monomers/Olduvai sequences, together contributing to a synergistic amplification effect.

Leveraging the T2T assembly to resolve rare and pathogenic inversions in reference genome gaps.

Chromosomal inversions (INVs) are particularly challenging to detect due to their copy-number neutral state and association with repetitive regions. Inversions represent about 1/20 of all balanced structural chromosome aberrations and can lead to disease by gene disruption or altering regulatory regions of dosage-sensitive genes in cis Short-read genome sequencing (srGS) can only resolve ∼70% of cytogenetically visible inversions referred to clinical diagnostic laboratories, likely due to breakpoints in repetitive regions. Here, we study 12 inversions by long-read genome sequencing (lrGS) (n = 9) or srGS (n = 3) and resolve nine of them. In four cases, the inversion breakpoint region was missing from at least one of the human reference genomes (GRCh37, GRCh38, T2T-CHM13) and a reference agnostic analysis was needed. One of these cases, an INV9 mappable only in de novo assembled lrGS data using T2T-CHM13 disrupts EHMT1 consistent with a Mendelian diagnosis (Kleefstra syndrome 1; MIM#610253). Next, by pairwise comparison between T2T-CHM13, GRCh37, and GRCh38, as well as the chimpanzee and bonobo, we show that hundreds of megabases of sequence are missing from at least one human reference, highlighting that primate genomes contribute to genomic diversity. Aligning population genomic data to these regions indicated that these regions are variable between individuals. Our analysis emphasizes that T2T-CHM13 is necessary to maximize the value of lrGS for optimal inversion detection in clinical diagnostics. These results highlight the importance of leveraging diverse and comprehensive reference genomes to resolve unsolved molecular cases in rare diseases.

Epigenetic control and inheritance of rDNA arrays.

Ribosomal RNA (rRNA) genes exist in multiple copies arranged in tandem arrays known as ribosomal DNA (rDNA). The total number of gene copies is variable, and the mechanisms buffering this copy number variation remain unresolved. We surveyed the number, distribution, and activity of rDNA arrays at the level of individual chromosomes across multiple human and primate genomes. Each individual possessed a unique fingerprint of copy number distribution and activity of rDNA arrays. In some cases, entire rDNA arrays were transcriptionally silent. Silent rDNA arrays showed reduced association with the nucleolus and decreased interchromosomal interactions, indicating that the nucleolar organizer function of rDNA depends on transcriptional activity. Methyl-sequencing of flow-sorted chromosomes, combined with long read sequencing, showed epigenetic modification of rDNA promoter and coding region by DNA methylation. Silent arrays were in a closed chromatin state, as indicated by the accessibility profiles derived from Fiber-seq. Removing DNA methylation restored the transcriptional activity of silent arrays. Array activity status remained stable through the iPS cell re-programming. Family trio analysis demonstrated that the inactive rDNA haplotype can be traced to one of the parental genomes, suggesting that the epigenetic state of rDNA arrays may be heritable. We propose that the dosage of rRNA genes is epigenetically regulated by DNA methylation, and these methylation patterns specify nucleolar organizer function and can propagate transgenerationally.

Novel crossover and recombination hotspots massively spread across primate genomes

BackgroundThe recombination landscape and subsequent natural selection have vast consequences forevolution and speciation. However, most of the crossover and recombination hotspots are yet to be discovered. We previously reported the relevance of C and G trinucleotide two-repeat units (CG-TTUs) in crossovers and recombination.MethodsOn a genome-wide scale, here we mapped all combinations of A and T trinucleotide two-repeat units (AT-TTUs) in human, consisting of AATAAT, ATAATA, ATTATT, TTATTA, TATTAT, and TAATAA. We also compared a number of the colonies formed by the AT-TTUs (distance between consecutive AT-TTUs < 500 bp) in several other primates and mouse.ResultsWe found that the majority of the AT-TTUs (> 96%) resided in approximately 1.4 million colonies, spread throughout the human genome. In comparison to the CG-TTU colonies, the AT-TTU colonies were significantly more abundant and larger in size. Pure units and overlapping units of the pure units were readily detectable in the same colonies, signifying that the units were the sites of unequal crossover. We discovered dynamic sharedness of several of the colonies across the primate species studied, which mainly reached maximum complexity and size in human.ConclusionsWe report novel crossover and recombination hotspots of the finest molecular resolution, massively spread and shared across the genomes of human and several other primates. With respect to crossovers and recombination, these genomes are far more dynamic than previously envisioned.

Oligodendrocyte-specific expression of PSG8-AS1 suggests a role in myelination with prognostic value in oligodendroglioma

The segmentally duplicated Pregnancy-specific glycoprotein (PSG) locus on chromosome 19q13 may be one of the most rapidly evolving in the human genome. It comprises ten coding genes (PSG1-9, 11) and one predominantly non-coding gene (PSG10) that are expressed in the placenta and gut, in addition to several poorly characterized long non-coding RNAs. We report that long non-coding RNA PSG8-AS1 has an oligodendrocyte-specific expression pattern and is co-expressed with genes encoding key myelin constituents. PSG8-AS1 exhibits two peaks of expression during human brain development coinciding with the most active periods of oligodendrogenesis and myelination. PSG8-AS1 orthologs were found in the genomes of several primates but significant expression was found only in the human, suggesting a recent evolutionary origin of its proposed role in myelination. Additionally, because co-deletion of chromosomes 1p/19q is a genomic marker of oligodendroglioma, expression of PSG8-AS1 was examined in these tumors. PSG8-AS1 may be a promising diagnostic biomarker for glioma, with prognostic value in oligodendroglioma.

The identification of retro-DNAs in primate genomes as DNA transposons mobilizing via retrotransposition.

Mobile elements (MEs) constitute a major portion of the genome in primates and other higher eukaryotes, and they play important role in genome evolution and gene function. MEs can be divided into two fundamentally different classes: DNA transposons which transpose in the genome in a "cut-and-paste" style, and retrotransposons which propagate in a "copy-and-paste" fashion via a process involving transcription and reverse-transcription. In primate genomes, DNA transposons are mostly dead, while many retrotransposons are still highly active. We report here the identification of a unique group of MEs, which we call "retro-DNAs", for their combined characteristics of these two fundamentally different ME classes. A comparative computational genomic approach was used to analyze the reference genome sequences of 10 primate species consisting of five apes, four monkeys, and marmoset. From our analysis, we identified a total of 1,750 retro-DNAs, representing 748 unique insertion events in the genomes of ten primate species including human. These retro-DNAs contain sequences of DNA transposons but lack the terminal inverted repeats (TIRs), the hallmark of DNA transposons. Instead, they show characteristics of retrotransposons, such as polyA tails, longer target-site duplications (TSDs), and the "TT/AAAA" insertion site motif, suggesting the use of the L1-based target- primed reverse transcription (TPRT) mechanism. At least 40% of these retro-DNAs locate into genic regions, presenting potentials for impacting gene function. More interestingly, some retro-DNAs, as well as their parent sites, show certain levels of expression, suggesting that they have the potential to create more retro-DNA copies in the present primate genomes. Although small in number, the identification of these retro-DNAs reveals a new mean for propagating DNA transposons in primate genomes without active canonical DNA transposon activity. Our data also suggest that the TPRT machinery may transpose a wider variety of DNA sequences in the genomes.

Characterization of the genetic variation and evolutionary divergence of the CLEC18 family.

The C-type lectin family 18 (CLEC18) with lipid and glycan binding capabilities is important to metabolic regulation and innate immune responses against viral infection. However, human CLEC18 comprises three paralogous genes with highly similar sequences, making it challenging to distinguish genetic variations, expression patterns, and biological functions of individual CLEC18 paralogs. Additionally, the evolutionary relationship between human CLEC18 and its counterparts in other species remains unclear. To identify the sequence variation and evolutionary divergence of human CLEC18 paralogs, we conducted a comprehensive analysis using various resources, including human and non-human primate reference genome assemblies, human pangenome assemblies, and long-read-based whole-genome and -transcriptomesequencing datasets. We uncovered paralogous sequence variants (PSVs) and polymorphic variants (PVs) of human CLEC18 proteins, and identified distinct signatures specific to each CLEC18 paralog. Furthermore, we unveiled a novel segmental duplication for human CLEC18A gene. By comparing CLEC18 across human and non-human primates, our research showed that the CLEC18 paralogy probably occurred in the common ancestor of human and closely related non-human primates, and the lipid-binding CAP/SCP/TAPS domain of CLEC18 is more diverse than its glycan-binding CTLD. Moreover, we found that certain amino acids alterations at variant positions are exclusive to human CLEC18 paralogs. Our findings offer a comprehensive profiling of the intricate variations and evolutionary characteristics of human CLEC18.

The identification of retro-DNAs in primate genomes as DNA transposons mobilizing via retrotransposition

Background Mobile elements (MEs) constitute a major portion of the genome in primates and other higher eukaryotes, and they play important role in genome evolution and gene function. MEs can be divided into two fundamentally different classes: DNA transposons which transpose in the genome in a “cut-and-paste” style, and retrotransposons which propagate in a “copy-and-paste” fashion via a process involving transcription and reverse-transcription. In primate genomes, DNA transposons are mostly dead, while many retrotransposons are still highly active. We report here the identification of a new type of MEs, which we call “retro-DNAs”, for their combined characteristics of these two fundamentally different ME classes. Methods A comparative computational genomic approach was used to analyze the reference genome sequences of 10 primate species consisting of five apes, four monkeys, and marmoset. Results From our analysis, we identified a total of 1,750 retro-DNAs, representing 748 unique insertion events in the genomes of ten primate species including human. These retro-DNAs contain sequences of DNA transposons but lack the terminal inverted repeats (TIRs), the hallmark of DNA transposons. Instead, they show characteristics of retrotransposons, such as polyA tails, longer target-site duplications (TSDs), and the “TT/AAAA” insertion site motif, suggesting the use of the L1-based target-primed reverse transcription (TPRT) mechanism. At least 40% of these retro-DNAs locate into genic regions, presenting potentials for impacting gene function. More interestingly, some retro-DNAs, as well as their parent sites, show certain levels of expression, suggesting that they have the potential to create more retro-DNA copies in the present primate genomes. Conclusions Although small in number, the identification of these retro-DNAs reveals a new mechanism for propagating DNA transposons in primate genomes without active canonical DNA transposon activity. Our data also suggest that the TPRT machinery may transpose a wider variety of DNA sequences in the genomes.

Structurally divergent and recurrently mutated regions of primate genomes

We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, and marmoset. We identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes and 136,932 regulatory elements, including the most complete set of human-specific fixed differences. We estimate that 819.47 Mbp or ∼27% of the genome has been affected by SVs across primate evolution. We identify 1,607 structurally divergent regions wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost (e.g., CARD, C4, and OLAH gene families) and additional lineage-specific genes are generated (e.g., CKAP2, VPS36, ACBD7, and NEK5 paralogs), becoming targets of rapid chromosomal diversification and positive selection (e.g., RGPD gene family). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species.

Phylogenetic conservation of Trop-2 across species-rodent and primate genomics model anti-Trop-2 therapy for pre-clinical benchmarks.

A phylogenetic conservation analysis of Trop-2 across vertebrate species showed a high degree of sequence conservation, permitting to explore multiple models as pre-clinical benchmarks. Sequence divergence and incomplete conservation of expression patterns were observed in mouse and rat. Primate Trop-2 sequences were found to be 95%-100% identical to the human sequence. Comparative three-dimension primate Trop-2 structures were obtained with AlphaFold and homology modeling. This revealed high structure conservation of Trop-2 (0.66 ProMod3 GMQE, 0.80-0.86 ± 0.05 QMEANDisCo scores), with conservative amino acid changes at variant sites. Primate TACSTD2/TROP2 cDNAs were cloned and transfectants for individual ORF were shown to be efficiently recognized by humanized anti-Trop-2 monoclonal antibodies (Hu2G10, Hu2EF). Immunohistochemistry analysis of Macaca mulatta (rhesus monkey) tissues showed Trop-2 expression patterns that closely followed those in human tissues. This led us to test Trop-2 targeting in vivo in Macaca fascicularis (cynomolgus monkey). Intravenously injected Hu2G10 and Hu2EF were well tolerated from 5 to 10mg/kg. Neither neurological, respiratory, digestive, urinary symptoms, nor biochemical or hematological toxicities were detected during 28-day observation. Blood serum pharmacokinetic (PK) studies were conducted utilizing anti-idiotypic antibodies in capture-ELISA assays. Hu2G10 (t1/2 = 6.5days) and Hu2EF (t1/2 = 5.5days) were stable in plasma, and were detectable in the circulation up to 3weeks after the infusion. These findings validate primates as reliable models for Hu2G10 and Hu2EF toxicity and PK, and support the use of these antibodies as next-generation anti-Trop-2 immunotherapy tools.

Efficient genome monomer higher-order structure annotation and identification using the GRMhor algorithm.

Tandem monomeric units, integral components of eukaryotic genomes, form higher-order repeat (HOR) structures that play crucial roles in maintaining chromosome integrity and regulating gene expression and protein abundance. Given their significant influence on processes such as evolution, chromosome segregation, and disease, developing a sensitive and automated tool for identifying HORs across diverse genomic sequences is essential. In this study, we applied the GRMhor (Global Repeat Map hor) algorithm to analyse the centromeric region of chromosome 20 in three individual human genomes, as well as in the centromeric regions of three higher primates. In all three human genomes, we identified six distinct HOR arrays, which revealed significantly greater differences in the number of canonical and variant copies, as well as in their overall structure, than would be expected given the 99.9% genetic similarity among humans. Furthermore, our analysis of higher primate genomes, which revealed entirely different HOR sequences, indicates a much larger genomic divergence between humans and higher primates than previously recognized. These results underscore the suitability of the GRMhor algorithm for studying specificities in individual genomes, particularly those involving repetitive monomers in centromere structure, which is essential for proper chromosome segregation during cell division, while also highlighting its utility in exploring centromere evolution and other repetitive genomic regions. Source code and example binaries freely available for download at github.com/gluncic/GRM2023.

Deciphering the Role of Rapidly Evolving Conserved Elements in Primate Brain Development and Exploring Their Potential Involvement in Alzheimer's Disease.

Although previous studies have identified human-specific accelerated regions as playing a key role in the recent evolution of the human brain, the characteristics and cellular functions of rapidly evolving conserved elements (RECEs) in ancestral primate lineages remain largely unexplored. Here, based on large-scale primate genome assemblies, we identify 888 RECEs that have been highly conserved in primates that exhibit significantly accelerated substitution rates in the ancestor of the Simiiformes. This primate lineage exhibits remarkable morphological innovations, including an expanded brain mass. Integrative multiomic analyses reveal that RECEs harbor sequences with potential cis-regulatory functions that are activated in the adult human brain. Importantly, genes linked to RECEs exhibit pronounced expression trajectories in the adult brain relative to the fetal stage. Furthermore, we observed an increase in the chromatin accessibility of RECEs in oligodendrocytes from individuals with Alzheimer's disease (AD) compared to that of a control group, indicating that these RECEs may contribute to brain aging and AD. Our findings serve to expand our knowledge of the genetic underpinnings of brain function during primate evolution.

Comparative transcriptome analysis between rhesus macaques ( Macaca mulatta) and crab-eating macaques ( M. fascicularis).

Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques ( Macaca mulatta, MMU) and crab-eating macaques ( M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from 84 samples (41 MFA samples and 43 MMU samples) encompassing 14 common tissues. Our findings revealed a small fraction of genes (3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover, 19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary, this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics.

Next-generation primate genomics: New genome assemblies unlock new questions

Nonhuman primates provide unique evolutionary and comparative insight into the human phenotype. Genome assemblies are now available for nearly half of the species in the primate order, expanding our understanding of genetic variation within and between species and making important contributions to evolutionary biology, evolutionary anthropology, and human genetics.

Retraction and replacement of: The relationship between sexual dimorphism and androgen response element proliferation in primate genomes.

Retraction and replacement of: The relationship between sexual dimorphism and androgen response element proliferation in primate genomes.