Medical Genetics - V. M. Zaporozhan 2005

Introduction to Medical Genetics
Molecular Basis of Heredity
Gene Expression

Gene Expression refers to the realization of the Genetic information encoded within a gene (Fig. 1.7). According to the Central dogma of molecular biology, this process follows the directional flow:

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The initial stage of genetic information expression is METABOLISM/31.html">Transcription, a process whereby the DNA nucleotide sequence is transcribed into an RNA sequence. Transcription takes place within the Cell Nucleus along the template DNA strand according to THE PRINCIPLE OF complementarity. The resulting RNA molecule possesses an exon-intron Structure and is immature (pre-mRNA). During its maturation (Processing), introns are excised, exons are joined together (splicing), a methylguanosine cap is added to the 5' end (capping), and a poly-A tail is attached to the 3' end (polyadenylation). Processing yields mature mRNA. These post-transcriptional modifications are essential for mRNA export into the Cytoplasm, increase molecular stability, and facilitate ribosome binding to the mRNA.

Subsequently, the mRNA is transported into the cytoplasm to undergo Translation, or Protein Synthesis. Ribosomes attach to the mRNA and move along its strand, synthesizing a polypeptide chain in accordance with The nucleotide sequence. tRNA molecules also play an essential role in translation.

The newly synthesized polypeptide undergoes post-translational modifications, including The formation of its proper spatial STRUCTURE AND AMINO acid alterations.

Modern concepts regarding the realization of hereditary information are somewhat broader. First, a protein may consist of multiple Polypeptides and thus be encoded by several genes (e.g., Hemoglobin). Conversely, a single gene can encode multiple polypeptides through mechanisms such as:

— each strand of a double-stranded DNA fragment can encode its own protein;

— intronic regions within a gene can encode independent, small Proteins;

— alternative promoters or different reading frames of genetic information can exist within a single gene (leading to distinct transcription start sites, and consequently different mRNAs and proteins);

— Alternative Splicing and alternative polyadenylation occur during RNA maturation, resulting in the formation of diverse mature mRNAs;

— recently, The process of mature mRNA editing in the cytoplasm has been discovered, involving the substitution of individual NUCLEOTIDES, which can induce premature stop codons and the synthesis of a truncated protein chain.

Fig. 1.7. Schematic diagram of genetic Information Flow in a Introduction/5.html">Eukaryotic Cell

These and presumably other, yet undiscovered mechanisms explain why, despite having only about 30,000 protein-coding genes, The Human Body synthesizes roughly 250,000 different proteins during ontogenesis.

It is now well established that the readout of genetic information is not strictly unidirectional (DNA→RNA). Messenger RNA can serve as a template for DNA Synthesis (RNA→DNA), a process known as reverse transcription. The resulting DNA lacks introns and is termed cDNA (complementary DNA). Although nucleic acid synthesis directed by a protein template has not yet been proven, it has been demonstrated that certain exogenous proteins (Prions) are capable of altering the spatial conformation and properties of homologous endogenous proteins within the Organism.