Genomes and Their Evolution

21.1 Describe how the Human Genome Project contributed to DNA sequencing technology.
21.2 Explain how scientists use bioinformatics to analyze genomes and their functions.
21.3 Compare and contrast genome size, number of genes, and gene density across diverse genomes.
21.4 Describe the composition of the genome of a multicellular eukaryote, such as humans.
21.5 Identify the changes to DNA that contribute to the evolution of the genome.
21.6 Explain how comparing genome sequences and developmental processes helps in understanding evolution.

Genome: An entire set of DNA instructions found in a cell, which is required for the development and functions of organisms.

Officially begun in 1990, with the sequencing of the human genome published in 2006.
Goal of the Human Genome Project is to determine the complete nucleotide sequence of each chromosome.
J. Craig Venter utilized a whole-genome shotgun approach to sequence the entire genome, elucidating unique human genes compared to other organisms (e.g., dolphins, seaweed).
Whole-genome shotgun (WGS) approach:
- Involves cloning and sequencing fragments of randomly cut DNA, which are then assembled into a continuous sequence.

The WGS approach remains relevant; however, newer “next-generation” sequencing techniques are emerging.
Features of next-generation techniques:
- Do not require cloning steps.
- Facilitate a metagenomics approach (sequencing DNA from groups of species in environmental samples).
- Capable of generating large amounts of data rapidly.

Genomics: The study of whole sets of genes and their interactions.
Complete genome sequences exist for various organisms, including humans, chimpanzees, E. coli, and more.
Comparison of genomes provides insights into evolution and biological processes.

Bioinformatics: A field combining biology and informatics (computer science) for storing, analyzing, and distributing biological data, primarily DNA and protein sequences.
Key bioinformatics resources include:
- National Center for Biotechnology Information (NCBI)
- European Molecular Biology Laboratory
- DNA Data Bank of Japan
- BGI in Shenzhen, China.
GenBank: The NCBI database for sequences, which is continuously updated.
NCBI BLAST:
- Basic Local Alignment Search Tool that allows users to search specific DNA sequences, protein sequences, and common stretches of amino acids.

Domains: Distinct functional and/or structural units within protein/DNA; usually responsible for particular functions.
Gene annotation involves automated identification of protein-coding genes, searching for translational start and stop signals, RNA splicing sites, and promoter sequences.
Comparison with genes across species aids in understanding gene functions.

Proteomics: The study of large sets of proteins and their properties.
A proteome refers to the complete set of proteins expressed by a cell or group of cells.
Systems biology focuses on functional integration of genes and proteins, producing network-like functional maps of interactions.

The Cancer Genome Atlas Project: Completed in 2018 with significant contributions to understanding tumor generation.
Utilizes DNA microarrays and RNA-seq to assess gene expression in cancer patients, enabling personalized treatments based on genetic profiles.

Genomes vary in size, the number of genes, and gene density.
Bacteria and archaea genomes range from 1 to 6 million base pairs (Mb) with 1,500 to 7,500 genes.
Eukaryotic genomes are generally larger, with plants and animals exceeding 100 Mb; humans possess a genome of approximately 3,000 Mb.
There is no direct correlation between the number of genes and genome size in eukaryotes.

Multicellular eukaryotes, including humans, exhibit extensive noncoding DNA and multigene families.
Humans have relatively low gene density, with 98.5% of the genome noncoding, consisting of regulatory sequences, introns, and other nonfunctional DNA like pseudogenes and repetitive DNA.

Transposable elements are DNA segments that can move within the genome, constituting about 75% of human repetitive DNA.
Discovered through Barbara McClintock's experiments, transposable elements can impact genome evolution by altering gene functions and modulating gene expression.

Mutations are fundamental to genomic change and evolution. Increased genome sizes provide raw material for gene diversification.
Polyploidy occurs when chromosomes duplicate, allowing genes to diverge through mutation.
Unequal crossing during meiosis can lead to genetic deletions and duplications.

Duplication of genes allows one copy to evolve new functions while the other maintains the original function.
Example: The lysozyme gene duplicated and evolved into α-lactalbumin, playing a crucial role in milk production in mammals.

Humans exhibit 23 pairs of chromosomes while chimpanzees have 24 pairs due to ancestral chromosomal fusions post-divergence.
Such chromosomal changes can facilitate speciation.

Genome comparisons across species reveal evolutionary relationships and functional insights regarding conserved genes, vital for understanding overall biological processes and developments.
Evo-devo: Evolutionary developmental biology that studies conserved developmental genes, such as Hox genes, which regulate body plans and developmental processes across many species.

The FOXP2 gene is implicated in vocalization and language acquisition; mutations within this gene lead to significant speech impairments in humans.

Homeotic genes possess a conserved sequence known as the homeobox, critical for developmental regulation in multicellular organisms.
Conservation highlights significant evolutionary links across diverse species and developmental processes.

Invitation for discussion on key slides and concepts, encouraging explanation among peers as a form of reinforcing learning.