Dissecting the Current Genomics Landscape

Genomics is a discipline aimed at understanding the integral functioning of the complete set of genes (i.e., the genome) present in a cell, as well as the interaction of genes with the environment. In medicine, for example, genomics provides the basis for the prevention, diagnostics, and treatment of diverse diseases. This field is now undergoing exponential development mainly due to the evolution of new high-throughput sequencing platforms and genomic technologies.

Genomics

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A Brief History of Genomics

In 1977, the English biochemist Frederick Sanger developed a method based on DNA replication to determine the linear order of nucleotides (DNA) in a given genomic sequence. The method, popularly known as "Sanger sequencing", was first used to determine the entire genome sequence of the bacteriophage phiX174 (5386 nucleotides long).

The Human Genome Project (1990) was the first research effort aimed at determining the complete human genome sequence. In 2003, the International Human Genome Sequencing Consortium announced the completion of this project, a physical mapping containing more than 20,000 human genes in approximately 3 billion nucleotide base pairs.

What does Genomics Landscape mean?

Genomics is a wide discipline that deals with the full set of genes of a given cell and how the genome can shape a phenotype in particular environmental conditions (e.g., temperature, humidity, sunlight, etc.). The genomics field is based on our knowledge of the linear order of nucleotides of the DNA sequence, thereby being sequencing technologies fundamental within this field.

Human genomics is exponentially expanding as new knowledge in genomics emerges, allowing a better understanding of the complex relationships between the genome and disease states. Comparative genomics plays a crucial role because this subfield has the potential to compare nucleotide sequences in unrelated individuals and/or species, thereby recognizing how variation sources and signaling pathways are associated with disease states.

Implications of the Genomics Landscape

The Genomics Landscape involves a wide spectrum of related subdisciplines and application areas:

  • Functional Genomics. It aims to understand the overall functioning of the genome in a cell that develops in a given set of environmental conditions. Functional Genomics studies how genes and non-coding genomic sequences synergistically act during the establishment of developmental patterns that shape phenotypic characteristics or cellular traits. This subdiscipline has been one of the hottest topics in molecular biology and has undergone exponential growth over the last decades.
  • Structural Genomics. It is aimed at shedding light on the structural features of a genome, including its tridimensional conformation and topologically associating domains (TADs). Structural genomics encompasses several topics in genetics, including genomic mapping,  physical mapping, and sequencing technologies. The recent development of computational-driven structural genomics approaches has also been very useful in predicting the 3D structure of proteins based on sequence homology data.
  • Comparative Genomics. It aims to understand how structure-function relationships can be used to elucidate the evolution of genomic (coding and non-coding) sequences. Comparative genomics is required to establish a comparative evolutionary-driven framework between conserved nucleotide sequences of unrelated species, such as humans and yeast, rather than similar ones. In this regard, yeast (Saccharomyces cerevisiae) and fruit fly (Drosophila melanogaster) have been very useful model organisms for comparative genomics studies and helped to unravel the function of genes in different taxonomic groups, including vertebrate mammals.
  • Epigenomics. It is a subdiscipline aimed at describing how chemical modifications that do not involve changes in the nucleotide sequence of a genome can act to affect gene expression. Epigenetic mechanisms include chemical modifications such as DNA methylation and histone modifications (e.g., histone acetylation, histone methylation, etc.), as well as associated non-coding RNA (ncRNA) pathways. These mechanisms synergistically work in a mutually reinforced way to shape gene expression patterns in particular environments and cellular contexts.
  • Metagenomics. It aims to sequence and analyze the genomes of microorganisms obtained from a bulk sample.
  • Genomic technologies. It includes a broad range of applications, including genome editing strategies (CRISPR-Cas, transcription activator-like effector nucleases), RNA-based approaches (RNA interference, RNA activation, mRNA-based vaccines), recombinant DNA technologies, etc.

Genomics

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Future Perspectives

The genomics landscape is constantly changing as technological advancements are developed, making new technologies more versatile and accessible. Genomics technologies enable us to exploit the potential of the genome to control target gene expression, which has major importance in virtually any biotechnological application field ranging from treating genetic diseases to flavoring foods.

The CRISPR-Cas system has likely been the last player in this fascinating field, but even more powerful technologies are expected to become over the next few years. For example, genomics is now discovering the potential that endogenous mobile elements (transposons and retrotransposons) pose to modulate gene expression patterns, which surely will lead to a new revolution in genomics. We need to be prepared for the future of a field that will continue producing amazing technologies and new methodologies.

Sources:

  • Giaever, Guri, and Corey Nislow. "The yeast deletion collection: a decade of functional genomics." Genetics 197.2 (2014): 451-465. DOI https://doi.org/10.1534/genetics.114.161620.
  • Pinheiro, Inês, Maria-Elena Torres-Padilla, and Geneviève Almouzni. "Epigenomics in the single cell era, an important read out for genome function and cell identity." Epigenomics 13.13 (2021): 981-984. DOI https://doi.org/10.2217/epi-2021-0153.
  • Przybyla, Laralynne, and Luke A. Gilbert. "A new era in functional genomics screens." Nature Reviews Genetics 23.2 (2022): 89-103. DOI https://doi.org/10.1038/s41576-021-00409-w.
  • Rogers, Jeffrey, and Richard A. Gibbs. "Comparative primate genomics: emerging patterns of genome content and dynamics." Nature Reviews Genetics 15.5 (2014): 347-359. DOI https://doi.org/10.1038/nrg3707.

Further Reading

Last Updated: Nov 28, 2022

Dr. Luis Vaschetto

Written by

Dr. Luis Vaschetto

After completing his Bachelor of Science in Genetics in 2011, Luis continued his studies to complete his Ph.D. in Biological Sciences in March of 2016. During his Ph.D., Luis explored how the last glaciations might have affected the population genetic structure of Geraecormobious Sylvarum (Opiliones-Arachnida), a subtropical harvestman inhabiting the Parana Forest and the Yungas Forest, two completely disjunct areas in northern Argentina.

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