What do you mean by Genomics?

Genes are responsible for transmitting the characters located on the chromosomes from one individual to another across the generations. Genetics is the study of different genes that are involved in different functions. Genetics is a branch of biology that studies genes, genetic diversity, and heredity in living organisms. The genetic system consists of genetic notations, which is a system of signs and symbols. Genotype refers to the organism's genetic composition, and phenotype refers to the observable property of the organism.

Genetics serves the following functions: -

• It should store and express the genetic information for conferring the heritable characters of the living organisms.
• For evolution to happen, the sequences of DNA should have the ability to mutate themselves to undergo the process of mutation.
• For transmitting the copy of DNA, a gene should have the ability to replicate itself.

The term "genomics" was given by Thomas Roderick in 1987. Genomics includes determining the structure (including DNA sequences) and function of an organism's genome. The entire complement of the genetic material of an organism, virus, or organelle, the haploid set of chromosomes of a eukaryotic organism, its whole sequence are all covered under the term genomics.

The Human Genome Project officially began on October 1, 1990. The first genomic sequencing was performed for Haemophilus influenza.  The sequencing of the E. coli whole genome was completed in the year 1997. Yeast (Saccharomyces cerevisiae) was the first eukaryotic genome whose sequencing was done in 1999. In recent times, whole-genome sequencing is performed for studying the Coronavirus genome for developing a vaccine against COVID-19.

Types of Genomics

• Comparative genomics
• Functional genomics

Comparative Genomics

The study of differences and similarities in the genomic structure (DNA or RNA) and organization of different organisms is called Comparative Genomics.

The objectives of comparative genomics are:

• To understand the process of evolution and
• To convert the sequencing of DNA data into proteins of known functions.

It is also considered important as it involves analyzing the different types of disease by considering the human genetics analogy as a model organism.

Orthologs are homologous genes that are found in different organisms, encode proteins having the same function. Evolved by the direct vertical descent and have diverged simply by the accumulating mutations.

In contrast, paralogs comprise sequences of genomic DNA within the same organism. These encode proteins that are related but have non-identical functions. Evolved by duplication, then followed by mutation accumulation.

Many proteins are compared to discrete domains; such proteins are called mosaic proteins. Example: Serine protease evolved in blood coagulation. The majority of proteins are extracellular. Mosaic proteins are found in unicellular organisms as well. The study of the gene that encodes mosaic proteins reveals a strong correlation between domain organization and intron-exon structure.

New combinations of exon are produced by recombination within the intron sequences. This is called exon shuffling. It produces new genes that encode proteins with altered functions. That can be responsible for mutating different genetic makeup that arises mutated disease.

SNPs (Single nucleotide polymorphism) are the variations in a nucleotide sequence that occur due to change even in a single base (adenine, guanine, thymine, cytosine). Therefore, it is estimated that 90% of genetic sequencing variation in the human genome is due to SNPs.

Examples of Comparative genomics:

Databases for comparative genomics

• Pedant: The database gives information about the proteins, their three-dimensional structure, enzyme patterns, etc.
• COGs: COGs (clusters of orthologous groups) can simplify evolutionary analyses of whole genomes and enhance the functional assignment of individual proteins.
• KEGG: Kyoto Encyclopedia of genes and genomes.
• MBGD: Microbial genome database, this database help to search for microbial genomes. This database also contains information on functions such as hydrocarbon breakdown and nucleotide biosynthesis, among others.

Example

Comparative genomics of Mitochondria and Chloroplast:

1) Animal and fungal mitochondrial genomic DNA is much smaller (15-20kb) than plant mitochondrial DNA (200-2000kb).

2) Gene from mitochondrial DNA has been transferred into the nucleus. This transfer has stopped in animals, but it continues to occur in the case of plant proteins.

Functional Genomics

Functional genomics deals with studying the function of all gene sequences and their expression in a cell.

Functional genomics toolbar

Functional genomics is useful in understanding the biochemical and physiological function of every gene product and its complexes.

DNA or oligonucleotide microarray technology is used in the definition of functional genomics. 2Dgels and other technologies are used to determine mRNA. Functional genomics requires high throughput technologies for forward and reverse genetic sequence research.

Examples of tools are bioinformatics, SAGE, AFLP, MPSS, and 2D-gels.

Determination of function of unknown gene

Computer analysis: With the help of a computer, homology searching can be performed to create homologous genes that share the common evolutionary sequence similarity. Usually, identical sequences lack a pair of homologous chromosomes due to random changes by mutation.

Several programs are used for such types of analysis. A homology search is done with a nucleotide or an amino acid sequence. The homology domains have evolved by a single nucleotide change, or complex rearrangements result in new genes inside which the domains are present.

Homology analysis of Saccharomyces cerevisiaegenome was performed to assign new genes. Out of 6,000 genes, only 30% were identified by conventional methods and 90% by homology analysis.

Patterns of Gene expression

All the genes do not express, and only those genes express whose products are required by the cell.

A) Gene expression array by measuring levels of RNA transcripts

When a gene is switched on, it expresses through the formation of an RNA transcript. To approach this goal, specific RNA is extracted from the cell. By using this RNA, cDNA is synthesized and used as a hybridization probe.

The cDNA copy of the gene being studied is immobilized on a solid support. Then this DNA is hybridized with the hybridization probe synthesized from an RNA transcript. A hybridization signal is observed when the gene transcripts are present in the extract of RNA. For every coding gene in the genome, this method is repeated, and all the mRNA molecules of the cell are analyzed. This is called transcriptome.

B) Serial analysis of gene expression (SAGE)

C) DNA chip (DNA microarray) technology

A DNA array consists of sequences of DNA fixed on a solid support like a glass chip. There are several synonyms of microarrays, such as DNA chips, gene chips, DNA arrays, and biochips.

The DNA arrays are basically of two types:

• Spotted DNA arrays and
• Printed oligonucleotide chips.

a) In the case of a spotted DNA array, each array has several double-stranded molecules. The spots are very dense. The DNA molecules are typically 100-300bp long. They are obtained from genomic libraries, cDNA clones, or PCR amplification. Robots do spotting, and analysis is based on confocal scanning.

b) The printed oligonucleotide chips are produced by photolithography (a light-directed printing technology). These chips have single-stranded oligonucleotides of 20-25 bases. Non-overlapping oligonucleotides represent each sequence to reduce the false-positive results.

Context and Application

• Identification of tissue-specific genes (Example- Insulin gene in the Pancreas). It can diagnose a disease like diabetes mellitus in which destruction of beta cells occurs that are responsible for maintaining the insulin level in the blood.
• Discovery of drugs to treat various types of cancer or treatment of several diseases. For example- Insulin injection for daily administration, Thyroid hormone dose for managing a disease like Hypothyroidism.
• Study of variation in cell cycle
• Determining defects in regulatory sequences for diagnosing a disease or as a preventive measure.
• To determine the response to environmental parameters or treatment of any disease that includes mouth cancer, lung cancer, skin cancer, blood cancer, etc.

This topic is important for many entrance exams;

• Bachelors of Science (Botany, Zoology and Genomics)
• Masters of Science (Botany, Zoology and Genomics)