BIOL 1105 Test 4: Functional Genomics & Evolution Terms

What is the Study of Genomics?

integrates classical and molecular genetics to better understand genomes

Genomics

branch of biology that deals with mapping, annotating, and analyzing whole genomes

Two categories of genome maps

genetic maps and physical maps

genetic maps

derived from recombination frequency (linkage analysis) and provide relative locations of genes or genetic markers

Physical maps

precise position in the genome and often have a resolution at the nucleotide level

how is the distance between markers measured?

Distance between markers are measured in base pairs and large maps use kilobase pairs

Types of physical maps

restriction and chromosome

restriction maps

one of the first types of physical maps generated → created by digesting DNA with one or more restriction enzymes and mapping the location of the enzyme cut sites

chromosome maps

used by researchers who study whole chromosomes or genes which can translocate or move to other chromosomes → use various staining techniques, which identify regions of interest and can be viewed using a microscope

sequence tagged sites

small stretch of DNA, found at only one location in the genome → can be amplified using PCR

Principles of DNA sequencing

All sequencing methods rely on the polymerase chain reaction, electrophoresis, and the use of chain terminating nucleotides (earliest forms = dideoxynucleotides)

Manual sequencing

uses multiple reactions for sequencing + a lot of time and labor intensive

human genome project

project whose goal is to map, sequence, and identify all of the genes in the human genome

(First draft of genome project published in 2000 + result of 20+ years of work, and a collaboration between the US government and private biotech company called Celera)

how many human genes are predicted?

100,000

Genome annotation

assigns information about DNA to the genomic sequences

Coding sequences

DNA sequences that are used to produce protein or transcribes into functional RNAs, such as transfer RNA or ribosomal RNA

categories of noncoding DNA

introns, structural DNA, simple sequence repeats, and non coding RNA, segmental duplication, protein encoding genes, Pseudogenes, inactive genes, and transposable elements

ENCODE

Encyclopedia of DNA Elements = a collaborative effort which sought to identify all functional elements in the human genome

Why are conclusions of ENCODE controversial?

conclusions of ENCODE can be controversial, but the work done has contributed substantially to the mapping effort of the human genome

Genome analysis

Final component of genomics + concerned with identifying the role or purpose of DNA elements in the genome

primary approaches of genome analysis

comparative genomics, functional genomics, and proteomics

What is the hallmark of genomics?

synteny

what is synteny?

refers to the conserved arrangements of segments of DNA in related genomes + can be derived from comparing physical maps (possibly sequence data)

What does comparative genomics do?

Uses information from one genome to learn about a second genome

use of conserved or synthenous regions

Researchers use conserved or synthenous regions of known and unknown sequence to predict gene function, locate similar genes of interest, or predict evolutionary relatedness

3 categories of functional genomics

transcriptome, proteome, and the study of interactions between proteins

Transcriptome

the study of all RNA molecules produced by the genome

Proteome

the study of the proteins produced by a genome

DNA microarray

tool that allows researchers to determine which genes are being turned on or expressed at a particular location or time + requires that the researcher design a microarray chip consisting of "known" genes believed to be of importance

RNA sequencing

uses next generation sequencing to capture all the mRNA transcripts bring created during a particular time

Two techniques of proteomics

mass spectrometry and protein microarrays

mass spectrometry

calculates the charge to mass ratio of each peptide and compares those values with a database to identify the proteins

Protein microarray

work similar to DNA microarrays, however, instead of DNA sequences applied to the chip, antibodies are applied and used in the process of identifying the protein(s) in a sample

Bioinformatics

use of computer programming, mathematics, and modeling to analyze large amounts of biological data → application of bioinformatics to proteomics allows the rapid identification of proteins discovered

Applications of genomics

synthetic biology, health field, forensics

Development

describes the process by which a single celled fertilized egg (zygote) becomes a fully formed adult

Four major processes of development

cell division, cell differentiation, pattern formation, morphogenesis

Which processes of development continue throughout development

The earlier processes of cell division and differentiation

Why do researchers use model organisms to study development?

Model organisms tend to be less complex and therefore easier to study than humans + Use of model organisms avoids potential ethical concerns that can be associated with the experimental manipulation of human embryos

Examples of model organisms that are used to study development

C. elegans(nematodes), Drosophila melanogaster (fruit flies), and Xenopus laevis (African clawed frog)

Study of development: Xenopus laevis (African clawed frog)

Model for Cell Division & morphogenesis

Study of development: Drosophila melanogaster (fruit flies)

a Model for Cell Division and Differentiation

Study of development: Drosophila melanogaster (fruit flies)

Model for pattern Formation

Cell Division

Most obvious process required to transform a single celled zygote into a multicellular organism

Cell division in early embryonic cells:

cells do not exhibit G1 or G2 phases of the standard cell cycle → instead these cells only transition back and forth between S phase, to replicate DNA and the M phase to divide into daughter cells later

How does the length of the cell cycle increase?

Length of cell cycle increases after a certain number of cell cleavages have occurred (this is when the G1 and G2 phases return to the cell cycle)

What is the fastest rate of cell division at any point in an organism's life?

Cell cleavage in an early embryo

cell differentiation

the production of a specialized (differentiated) cell

How do differentiated cells arise?

Differentiated cells arise from the division of stem cells

Stem Cell

any cell which has not adopted a particular cell fate, and therefore has the potential to become one of a number of different types of cells

Concept of self renewal

When a stem cell divides, one daughter cell will give rise to cells that differentiate, while the other daughter cell replaces the original stem cell and retains the properties that are associated with stem cells (self renewal)

What does differentiation depend on?

Differentiation depends on changes in gene expression

The DNA sequence in every cell of a given organism is the same, but ....

different cell types will express different genes

Overall differentiation is best viewed as...

a gradual process that occurs over multiple cell divisions

How are stem cells categorized?

Stem cells are categorized by their potency

what is potency?

a term used to describe the range of possible cell fates the descendant cells may adopt

How many levels of stem cell potency are there?

4

Totipotent stem cells

highest level of potency → these stem cells are able to form all the tissues of an organism, including all the extraembryonic tissues that are required to support embryonic development

Pluripotent stem cells

second potency level → able to form all the tissues of an organism, but none of the extra embryonic tissues

Multipotent stem cells

have the ability to differentiate into only different cell types + cannot divide to form a complete organism

Unipotent stem cells

able to differentiate into one type of cell

Pattern Formation

During pattern formation, each body segment is formed at the correct location through the expression of homeobox containing genes (commonly called Hox genes)

Mutations in hox genes

Mutations in Hox genes can have dramatic effects, most notably causing one segment of the embryo to develop as a different segment

Morphogenesis

the generation of an organism's body form

Differences between pattern formation and morphogenesis

Pattern formation can be compared to the creation of blue prints, and morphogenesis can be compared to the actual construction of blue prints

How is morphogenesis achieved?

achieved through: cell growth, cell division, cell migration, changes in cell shape, and program cell death (apoptosis)

Cell Migration in Morphogenesis

In order for the body to develop properly, some cells must be able to migrate to different locations → cells migrate through extracellular matrix, a mixture of carbohydrates and proteins secreted by cells to provide them with support and protection

Cell Shapes in terms of Morphogenesis

Morphogenesis is associated with changes in the shape of many cells; changes are usually required in order for the cell to function properly in the embryo and/or the adult organism

Apoptosis

highly controlled process of cell death that is activated by the expression of genes in a cell death pathway (programmed cell death)

necrosis

cell death caused by injury -- burst to release contents into the extracellular matrix

What is apoptosis commonly used for?

sed to "sculpt" appendages or reduce cell numbers

examples of apoptosis usage

human embryos webbed toes and fingers + cells that make up the tail of an embryo

Nuclear reprogramming

reverses differentiation by resulting a differentiated cell to an undifferentiated stem cell state

Epigenetic Changes

chemical modifications of nucleotide bases and do not change the sequence of the cell's DNA, but they do influence gene expression, and are stable throughout cell divisions

Somatic Cell Nuclear Transfer (SCNT)

Reproductive cloning method in which the DNA of an adult donor's body cell is transferred into an unfertilized egg.

Direct Reprogramming

takes advantage of the fact that some of the transcription factors that are expressed only in stem cells have been identified

Reproductive cloning

created a genetically identical copy of an individual organism

therapeutic cloning

used to generate genetically identical tissues

Potential uses of cloning techniques

1. potential to allow reintroduction of extinct species

2. has the potential to provide rejection free organs and tissues

3. could provide treatments associated with autoimmune diseases

Evolution (general)

important and recurring theme in biology + term often used in a non-scientific sense to refer to any entity changing over time

Evolution in biology

defined as change in populations of organisms over time

Genetic variation

presence of different alleles in a population

Alles

different versions of the same gene

Variation Exists at Many Levels

Variation in populations can be studied at different levels, despite that genetic variation is associated with genetic code (examples = morphology, genes, proteins, and genomes)

Genotype

genetic constitution or makeup of an individual/organism

Phenotype

the result of an individual's genotype (inherited characteristics + environmental factors → climate, nutrition, presence or absence of predators = environmental factors)

Mechanisms of evolution

mutation, gene flow, genetic drift, and selection

primary focus of evolutionary biology

understanding the mechanisms of evolution or the factors that cause allele frequencies to change over time in a population

Mutation

any change in the base sequence of DNA = the ultimate source of genetic variation and gives rise to different alleles

Gene Flow

the movement of alleles from one population to another

Genetic Drift

Defined as the change in allele frequencies due to sampling error, often called random chance (has largest effect in small populations)

founder effect (genetic drift)

occurs when a new population is established, as it is unlikely that they carry a wide variation of alleles (new population will display a different allele frequency or even lack certain alleles all together)

bottleneck effect (genetic drift)

Effect refers to a situation in which a population loses genetic variation form a drastic reduction in size, only a small number of individuals are contributing games to the next generation of organisms to be produced

Potential causes of bottleneck effect

disease, natural disasters, or changes in the environment

Selection

the process of organisms leaving differential numbers of progeny based on phenotype and behavior

3 conditions must be met in order for evolution to occur by natural selection

1. Variation: Individuals within a population are variable

2. Difference in survival and reproduction: In every generation, some variants are more successful at surviving and reproducing than others. Those with more success are said to have higher "fitness"

3. Heritability: variations among individuals are passed from parent to offspring

Survival and Reproduction are not random

Individuals with the most favorable variations, those who are better are surviving and reproducing (more fit) = natural selected

Natural selection

A natural process resulting in the evolution of organisms best adapted to the environment.

Types of natural selection

Types of natural selection include, but are not limited to: selection to avoid predators, selection ton match climatic conditions, selection for pesticide resistance, and selection for microbial resistance

Interactions among evolutionary forces

When evolutionary forces interact, they can either work together or in opposition