Gene Annotation: Identifying Protein-Coding Genes

Identifying Protein-Coding Genes and Understanding Their Functions

• Gene annotation is the process of identifying protein-coding genes within DNA sequences in a database.
• Three lines of evidence are used to identify a gene:
  • Patterns in the DNA sequence indicating the presence of genes (e.g., translational start and stop signals, RNA splicing sites, promoter sequences).
  • Comparison of the sequence to known genes from other organisms.
  • RNA-seq or other methods to show that the relevant RNA is actually expressed from the proposed gene.

Understanding Genes and Gene Expression at the Systems Level

• Genomics provides insights into genome organization, regulation of gene expression, embryonic development, and evolution.
• The ENCODE (Encyclopedia of DNA Elements) project (2003-2012) aimed to identify functionally important elements in the human genome.
• The project extensively characterized histone and DNA modifications, chromatin structure, and compared results from different projects.
• About 75% of the genome is transcribed at some point in at least one cell type studied.
• Biochemical functions have been assigned to DNA elements making up at least 80% of the genome.

Systems Biology

• Proteomics is the study of large sets of proteins and their properties.
• A proteome is the entire set of proteins expressed by a cell or group of cells.
• Systems biology focuses on the functional integration of genes and proteins in biological systems.
• The approach is possible due to advances in bioinformatics.

Sequences Related to Transposable Elements

• Multiple copies of transposable elements and related sequences are scattered throughout eukaryotic genomes.
• In humans and other primates, a large portion of transposable element-related DNA consists of Alu elements.
• Many Alu elements are transcribed into RNA molecules, which may help regulate gene expression.

Genes and Multigene Families

• Many eukaryotic genes are present in one copy per haploid set of chromosomes.
• The rest of the genes occur in multigene families, collections of two or more identical or very similar genes.
• Some multigene families consist of identical DNA sequences, usually clustered tandemly, such as those that code for rRNA products.

Evolution of Genomes

• The basis of change at the genomic level is mutation, which underlies much of genome evolution.
• Duplication, rearrangement, and mutation of DNA contribute to genome evolution.
• Accidents in meiosis can lead to polyploidy, which can result in genes with novel functions.
• Alterations of chromosome structure, such as fusions and inversions, can also contribute to genome evolution.

Evolution of Genes with Novel Functions

• One copy of a duplicated gene can undergo alterations that lead to a completely new function for the protein product.
• For example, the lysozyme gene was duplicated and evolved into the gene that encodes α-lactalbumin in mammals.

Rearrangements of Parts of Genes

• Errors in meiosis can result in exon duplication or deletion.
• Exon shuffling can lead to mixing and matching of exons, either within a gene or between two nonallelic genes.

How Transposable Elements Contribute to Genome Evolution

• Multiple copies of similar transposable elements facilitate recombination, or crossing over, between different chromosomes.
• Insertion of transposable elements within a protein-coding sequence can block protein production.
• Insertion of transposable elements within a regulatory sequence can increase or decrease protein production.
• Transposable elements can also carry a gene or groups of genes to a new position or create new sites for alternative splicing in an RNA transcript.