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Genome sequencing has transformed biology by
allowing scientists to examine the entire genetic blueprint of an organism, rather than individual genes in isolation
The first genome ever sequenced
bacteriophage, an organism with an RNA genome that codes for only four protein( very simple)
the first eukaryotic genome
sequenced in 1996 and belonged to yeast (Saccharomyces cerevisiae).
eukaryotic genomes
are larger, contain repetitive DNA, and require more complex annotation
Caenorhabditis elegans
the first multicellular animal with a fully sequenced genome.
Repetitive DNA is a major sequencing challenge
consists of sequences that occur multiple times throughout the genome. These regions are notoriously difficult to sequence and assemble, because short reads cannot easily be assigned to their correct genomic location.
When sequencing a new organism, researchers face a fundamental trade-off between
depth versus breadth
Depth
refers to sequencing the same genome repeatedly to achieve high accuracy
Breadth
refers to sequencing many individuals or species with lower coverage.
Because sequencing generates massive amounts of data
data analysis and storage often cost more than the actual sequencing itself
The three major analytical stages in sequence generation
Primary Analysis
Secondary Analysis
Tertiary Analysis
Primary Analysis
Raw sequence data generated directly by the sequencing machine
Secondary Analysis
Quality control and filtering of reads to remove errors and artifacts
Tertiary Analysis
Integrating multiple datasets to make biological meaning, such as identifying genes under selection or comparing populations.
Genomics has historically been biased toward
model organisms, particularly vertebrates and mammals, because of their relevance to human biology
Why sequencing non-model organisms are important
genomic data from these organisms often reflect phylogenetic history, allowing scientists to reconstruct evolutionary relationships even in poorly studied taxa.
Comparative genomics
examines differences and similarities across genomes to understand function and evolution
When studying Comparative genomics researchers compare
Gene content
Gene order
Regulatory sequences
Non-coding DNA
Structural landmarks
Orthologous genes
diverged after a speciation event and often retain similar functions across species.
Paralogous genes
diverged after a gene duplication event, allowing new or specialized functions to evolve.
Comparing non-model organisms to model organisms provides
a starting point for testing speciation hypotheses, reconstructing evolutionary history, and guiding conservation decisions.
Types of Genomics
Evolutionary genomics (e.g. when vertebrates colonized land)
Population genomics
Landscape genomics / phylogenomics
Speciation genomics
Conservation genomics
Most of these fields would not exist without next-generation sequencing (NGS).
Transcriptomics
RNAs are being expressed
Proteomics
proteins produced and their structures
Metabolomics
hormones and signaling molecules
Epigenetics
heritable changes in gene expression without DNA sequence changes
What Are GMOs?
A Genetically Modified Organism (GMO) contains one or more genes from another organism, inserted using molecular biology techniques
Concerns About GMOs
Genetic pollution
Out-competition of wild types
Gene flow to new hosts
Effects on non-target species
Horizontal gene transfer mechanisms include
Conjugation (F plasmids)
Transformation (free DNA)
Transduction (virus-mediated)
CRISPR/Cas9 originates from
bacterial immune system used to silence viral DNA.
CRISPR/Cas9 allows
scientists to precisely cut and insert DNA sequences into almost any genome.
CRISPR enables
gene insertion and regulation, making it far more precise than earlier GMO techniques.