Biology subjects

Esteller-Cucala, P.

Publications and source records attributed to Esteller-Cucala, P..

3 recordsLinked to original sources

bioRxiv2022

Y chromosome sequence and epigenomic reconstruction across human populations

Recent advances in long-read sequencing technologies have allowed the generation and curation of more complete genome assemblies, enabling the analysis of traditionally neglected chromosomes, such as the human Y chromosome (chrY). Native DNA was sequenced on a MinION Oxford Nanopore Technologies sequencing device to generate genome assemblies for 7 major chrY human haplogroups. We analyzed and compared the chrY enrichment of sequencing data obtained using two different selective sequencing approaches: adaptive sampling and flow cytometry chromosome sorting. We show that adaptive sampling can produce data to create assemblies comparable to chromosome sorting while being a less expensive and time-consuming technique. We also assessed haplogroup-specific structural variants, which would be otherwise difficult to study using short-read sequencing data only. Finally, we took advantage of this technology to detect and profile epigenetic modifications amongst the considered haplogroups. Altogether, we provide a framework to study complex genomic regions with a simple, fast, and affordable methodology that could be applied to larger population genomics datasets.

genomics↗

bioRxiv2021

Transcriptome innovations in primates revealed by single-molecule long-read sequencing

Transcriptomic diversity greatly contributes to the fundamentals of disease, lineage-specific biology, and environmental adaptation. However, much of the actual isoform repertoire contributing to shaping primate evolution remains unknown. Here, we combined deep long- and short-read sequencing complemented with mass spectrometry proteomics in a panel of lymphoblastoid cell lines (LCLs) from human, three other great apes, and rhesus macaque, producing the largest full-length isoform catalog in primates to date. Our transcriptomes reveal thousands of novel transcripts, some of them under active translation, expanding and completing the repertoire of primate gene models. Our comparative analyses unveil hundreds of transcriptomic innovations and isoform usage changes related to immune function and immunological disorders. The confluence of these innovations with signals of positive selection and their limited impact in the proteome points to changes in alternative splicing in genes involved in immune response as an important target of recent regulatory divergence in primates.

evolutionary biology↗

bioRxiv2019

Gene regulatory architectures dissect the evolutionary dynamics of regulatory elements in humans and non-human primates

To gain insight into the evolution of the epigenetic regulation of gene expression in primates, we extensively profiled a new panel of human, chimpanzee, gorilla, orangutan, and macaque lymphoblastoid cell lines (LCLs), using ChIP-seq for five histone marks, ATAC-seq and RNA-seq, further complemented with WGS and WGBS. We annotated regulatory elements and integrated chromatin contact maps to define gene regulatory architectures, creating the largest catalog of regulatory elements in primates to date. We report that epigenetic conservation and its correlation with sequence conservation in primates depends on the activity state of the regulatory element. Our gene regulatory architectures reveal the coordination of different types of components and highlight the role of promoters and intragenic enhancers in the regulation of gene expression. We observed that most regulatory changes occur in weakly active intragenic enhancers. Remarkably, novel human-specific intragenic enhancers with weak activities are enriched in human-specific mutations. These elements appear in genes with signals of positive selection, tissue-specific expression and particular functional enrichments, suggesting that the regulatory evolution of these genes may have contributed to human adaptation.

evolutionary biology↗