Comparative Genomics + phylogenetics

Comparative Genomics

the field of genomics in which genomic features (gene content, function and genome organisation) are compared across different species to understand evolutionary relationships and functions.

Molecular Phylogenetics

Applies a combination of molecular and statistical techniques to infer evolutionary relationships among organisms or genes eg analysing genetic data, enabling the construction of phylogenetic trees that depict the history of species evolution.

Evolutionary Relationships

Connections between organisms based on genetic data.

ACE2 and its significance

A gene encoding angiotensin-converting enzyme 2 which is a receptor that SARS-cov 2 binds to in human cells, playing a crucial role in the entry of the virus and influencing the severity of COVID-19.

• Using comparative genomics we can see

Phylogenetics

Study of evolutionary relationships among biological entities.

SNP (Single Nucleotide Polymorphism)

Site in the genome where a single nucleotide differs between individuals of a species.

• To be considered a SNP, it must reach a frequency of 1% in a population

• Inherited as allelic variants in same way alleles produce phenotypic differences like blood types although SNPs don’t often produce phenotypic differences

Genetic Drift

Random changes in allele frequencies in a population.

Natural Selection

Process where organisms better adapted survive.

Genetic Engineering

Direct manipulation of an organism's genes.

Structural Genomics

Determines DNA sequences of entire genomes.

Human Genome Project

13-year project mapping the human genome.

Map-based Sequencing

Uses genetic maps to align sequenced fragments.

Whole-genome Shotgun Sequencing

Aligns fragments using sequence overlap.

Next-generation Sequencing

New technology for rapid genome data collection.

Bioinformatics Bottleneck

Challenge in processing vast genomic data.

Tree of Life

Universal tree representing all named species.

Myotis lucifugus

Little brown bat, key for evolutionary research.

Mammalian Genome Size

Bat has one of the smallest functional genomes.

Chromosomal Structure

Bat's chromosomes resemble ancestral mammalian state.

Metabolic Rate

Bat has highest rate among mammals, longevity.

Cancer-causing Free Radicals

Potentially managed by the little brown bat.

International Human Genome Consortium

Collaborative group for human genome sequencing.

Functional Elements

Coding and non-coding regions essential for research.

Phylogeny

Evolutionary history of a species or group.

Phylogenetic tree

Diagram representing evolutionary relationships.

Genealogical tree

Visual representation of lineage relationships.

Phylogenetic time

Chronological representation of evolutionary changes.

Systematics

Discipline classifying organisms by evolutionary relationships.

Taxonomy

Ordered division and naming of organisms.

Binomial Nomenclature

Two-part naming system for species.

Genus

First part of a species' scientific name.

Specific epithet

Unique second part of a species' name.

Hierarchical Classification

Grouping species into broad to narrow categories:

Domain

Kingdom

Phylum

Class

Order

Family

Genus

Species

Rhinolopus sp.

Genus of bats related to SARS-CoV-2.

Phylogenetic tree

Hypothesis about evolutionary relationships among species.

Branch point

Divergence point of two species in tree.

Sister taxa

Groups sharing an immediate common ancestor.

Rooted tree

Includes branch for last common ancestor.

Basal taxon

Diverges early near common ancestor of group.

Polytomy

Branch with more than two emerging groups.

Ancestral lineage

Lineage leading to common ancestor of taxa.

Phylogeny

Study of evolutionary history and relationships.

Common ancestor

Most recent ancestor shared by taxa.

Divergence

Separation of lineages from a common ancestor.

Minke whale

Species identified through phylogenetic analysis.

Humpback whale

Another species analyzed in phylogenetic studies.

Amino acid matrix

Data used for phylogenetic analysis of mammals.

Vertebrate outgroups

External taxa used to root phylogenetic trees.

Autocorrelated rates

Method for analyzing evolutionary rates in phylogeny.

Hard-bounded constraints

Limitations applied in phylogenetic analysis.

Whale meat

Identified species through phylogenetic methods.

Taxon

Group of one or more species in classification.

Evolutionary relationships

Connections between species based on ancestry.

Detection methods

Techniques used to identify species from samples.

Species identification

Determining species based on genetic analysis.

What is a genome

A genome is the complete set of biological information needed to build and maintain an organism

What molecule encodes the biological information in a genome

The biological information in a genome is encoded in deoxyribonucleic acid (DNA).

What is the goal of Structural Genomics

To sequence entire genomes and understand their structure

What major project aimed to sequence the human genome and what technologies helped lower the cost of human genome sequencing?

The Human Genome Project was a global scientific research initiative that aimed to map and understand all the genes of the human species, utilizing advancements in DNA sequencing technologies such as next-generation sequencing.

What are two main approaches used in genome sequencing

1. Map-based sequencing

2. Whole-genome shotgun sequencing

what are the differences b/w a genetic map and a physical map?

A genetic map shows the relative positions of genes based on recombination frequencies,

while a physical map provides the actual physical distances (kb,mb etc) between genes on a chromosome, measured in base pairs.

How does map-based genome sequencing work?

It relies on detailed genetic and physical maps to align sequenced fragments and reconstruct the genome by identifying overlapping sequences, effectively piecing together the entire genome from smaller segments.

what are the 6 steps of map-based sequencing?

1. Create a genetic map by partial digestion of DNA resulting in overlapping fragments that are cloned into bacterial artifical chromosomes (BACs)

2. Analyse the large-insert clones for genetic markers i.e using DNA probes / overlapping restriction sites

3. Assemble the DNA sequences from BACs into contiguous sequences (contigs).

4. Select a subset of overlapping clones that efficiently cover the entire chromosome which are then fractured + cloned

5. Sequence each small-insert clone and use sequence overlap to assemble them in the correct order

6. Assemble the final sequence by putting together the large clones sequences together + fill any gaps

contig

is a continuous sequence of DNA that's constructed from overlapping DNA fragments.

Contigs are essential in genome assembly, as they represent the longest contiguous stretch of the DNA sequence from sequenced DNA fragments.

How does whole-genome shotgun sequencing work

It uses sequence overlap to align sequenced fragments

what are the 4 steps of whole-genome shotgun sequencing

1. Fragment the genome into small pieces using physical or enzymatic methods.

2. Clone the fragments into vectors to create a library of cloned DNA.

3. Sequence the fragments using high-throughput sequencing technologies.

4. Assemble the overlaps between fragments to reconstruct the original genome using powerful computer software

How has the genome revolution impacted biology and medicine

New technologies, like next-generation sequencing, generate vast amounts of data that transform biological research and medicine

What is the biomedical importance of comparative genomics

Comparative genomics helps identify functional elements in the human genome, including coding and non-coding regions, by comparing genomes across species.

This approach leverages 100 million years of evolutionary history to advance biomedical research

Why is identifying functional elements in the human genome important for biomedical research

Functional elements, including both coding and non-coding regions, are key to understanding human biology and disease

How does comparative genomics aid biomedical research

It helps identify functional elements in the human genome by comparing it with other mammalian genomes

What is one of the most powerful ways to discover functional elements in the human genome

Cross-species comparisons with other mammalian genomes

What is the Darwin Tree of Life Project

A project aimed at sequencing the genomes of all eukaryotic living species in the UK and Ireland to create a comprehensive tree of life

Why is Myotis lucifungus (little brown bat) important for human health and evolutionary research

The little brown bat plays a role in human health by helping control insect populations, particularly mosquitoes.

It is also important in evolutionary research due to its unique immune system and adaptations to hibernation, providing insights into aging, disease resistance, and environmental adaptation

Why is sequencing the genome of Myotis lucifungus (little brown bat) important

Bats represent 25% of all mammalian diversity and have one of the smallest mammalian genome sizes, providing insights into the minimal DNA required for a functional mammalian genome

Why is sequencing the genome of Myotis lucifungus (little brown bat) important in terms of chromosomal structure

This bat's chromosomal structure is very similar to the putative ancestral mammalian chromosomal state, making it valuable for studying mammalian evolution

Why is sequencing the genome of Myotis lucifungus (little brown bat) important for understanding metabolism and aging

This bat has the highest metabolic rate of all mammals yet can live over 34 years, suggesting it may have an unusual way of dealing with cancer-causing free radicals

Why is sequencing the genome of Myotis lucifungus (little brown bat) important for studying immunity

Bats may have immunity to certain diseases, and by understanding their genome, we can identify immune system genes that could offer insights into natural immunity

What is phylogeny

Phylogeny is the evolutionary history of a species or group of species.

How can the evolutionary history of a group of organisms be represented

It can be represented in a diagram called a phylogenetic tree

What is a phylogenetic time tree

A phylogenetic time tree is a diagram that represents the evolutionary relationships and timelines of species, such as the mammalian families based on amino acid matrix analysis.

How was the phylogenetic time tree of mammalian families created

It was created based on an analysis of the amino acid matrix of 164 mammals, with constraints on autocorrelated rates and rooted with five vertebrate outgroups (chicken, zebrafinch, green anole, frog, and zebrafish).

how can phylogenetic trees be used in studying epidemiology?

Can be used to follow the transmission of Covid-19 around the globeby tracing viral lineages and understanding how the virus spreads between populations.

What does phylogeny show

Phylogeny shows the evolutionary history of a species or group of species

What is the discipline of systematics

Systematics classifies organisms and determines their evolutionary relationships

What data does systematics use to infer evolutionary relationships

Systematics uses fossil, molecular, and genetic data to infer evolutionary relationships

What is taxonomy

Taxonomy is the ordered division and naming of organisms

What are the two key features of Linnaeus' system of taxonomy

The two key features are two-part names for species and hierarchical classification

What is the two-part scientific name of a species called

It is called a binomial

What does the first part of a binomial name represent

The first part represents the genus

What is the second part of a binomial name called

The second part is called the specific epithet, which is unique for each species within the genus

How should a binomial name be written.

The first letter of the genus is capitalized, and the entire species name is italicized

What is an example of a binomial name

Homo sapiens

Are broader taxa comparable between lineages

No, broader taxa are not comparable between lineages.

For example, an order of snails has less genetic diversity than an order of mammals

How do systematists depict evolutionary relationships?

Systematists depict evolutionary relationships in branching phylogenetic trees

Can Linnaean classification and phylogeny differ from each other

Yes, Linnaean classification and phylogeny can differ from each other because classification is based on shared characteristics while phylogeny is based on evolutionary history.

What does a phylogenetic tree represent

A phylogenetic tree represents a hypothesis about evolutionary relationships

What does each branch point on a phylogenetic tree represent

Each branch point represents the divergence of two species

What are sister taxa

Sister taxa are groups that share an immediate common ancestor

What does a rooted phylogenetic tree include

A rooted tree includes a branch to represent the last common ancestor of all taxa in the tree

What is a basal taxon

A basal taxon diverges early in the history of a group and originates near the common ancestor of the group