AP Bio- Regulation 1: Genetics- Systems Perspectives

Development:

• Explain the role of cytoplasmic determinants and induction in contributing to development.
• Describe the relationship between determination and differentiation in a cell.
• Explain how positional information is conveyed to the cells in a developing organism.
• Explain the role of homeotic genes in contributing to the development of an animal.

Now that all of this genome data exists, it can be analyzed for patterns.

Evolution should leave signatures in the data. What do those signature look like?

Following a duplication of genetic information, gene sequences can mutate to acquire novel functions (or to become non-functional).

These processes occur at the chromosomal, gene, and intra-gene levels of genome organization.

Genomics:

• Explain how genomes are sequenced.
• Explain the role of bioinformatics in genomic analysis.
• Compare trends in the evolution of genomes.
• Describe the structure and function of transposable elements, simple sequence DNA, regulatory elements and exons in the human genome, and their relative precentages.
• Explain the genetic events that have led to the evolution of multi-gene families.
• Provide examples of evidence from genomic analysis that supports the evolution of humans from a common ancestor with apes, and other mammals.
• Explain how a duplication of genetic information can lead to the evolution of new genes with novel functions.

Developmental Genetics

Pattern Formation

Differentiation

How is a body plan established in a developing organism?

How do cells with the same genetic information acquire different structures and functions?

Positional Information

Bicoid: An Example

Cytoplasmic Determinants

The molecular signals that establish the body axes in a developing organism.

Much of the work on genetic development was done in Drosophila.

Bicoid is a protein that is present in a differential gradient in the unfertilized egg.

Cells that develop in a high concentration of bicoid become the anterior (head) of the organism.

Bicoid controls head development directly, so it is referred to as a "morphogen".

Clearly, something pretty important has to happen to get from (a) to (b)

Substances present in the cytoplasm of the egg cell that are unevenly distributed

Direct different gene expression in subsequent generations of cells.

Important in early development

Determination

Induction

Lots of work, done over a long period of time.

We'll look at one specific example.

Distribution of bicoid in normal fruit fly egg and early-stage embryo

Morphological differences between normal (top) and bicoid mutant (bottom) fruit fly larvae

Signals from surrounding cells that determine the course of a cell's genetic development.

Important in later development.

The regulatory events in a cell's genome that lead to differentiation of structure and function.

Once a cell commits to a particular fate, it can not uncommit.

Determination precedes differentiation.

Simplified diagram of determination leading to differentiation in a muscle cell

Developmental Regulators

Homeotic Genes

First discovered in Drosophila by Edward B. Lewis. Nobel Prize in 1995

Have since been discovered in all animal lineages.

Highly conserved sequences (what does that mean), including a characteristic "box" of bases called a "homeobox"

Florescence image showing 7 different homeobox expression patterns in a fruit fly embryo.

While vertebrates have more Homeotic genes than invertebrates, the sequences are very highly conserved.

Eyeless mutants have vestigial eyes in odd places

It quickly becomes clear why these experiments are done in fruit flies

Antennapedia mutants have legs in the wrong places

Differences in homeobox expression patterns lead directly to differences in segmentation

Genetics:

Big Questions

Make Sure You Can:

Regulatin' Genes

How does genetics contribute to the development of an organism?

How does evolution influence the structure of an organism's genetic code?

A Systems Perspective

Genomics

Genome Sequencing

What the Human Genome Looks Like

The Human Genome

Process

Analysis

Bioinformatics:

Computational analysis

of genetic data

Technology has made genome sequencing less and less costly

~3 times more introns than exons!

All protein & RNA coding sequences

To sequence a genome:

• Shred it in to bits
• Sequence the shreds
• Use a computer to line it all back up

SUPER IMPORTANT!

Transposable Elements!

Non-coding DNA segments that catalyze their own replication and movement throughout the genome

Discovered by Barbara McClintock in corn in 1940's. Nobel Prize in 1983.

2 Views of Genome Comparisons

The Human Genome Project Method

Whole-Genome "Shotgun" sequencing

Promoters, enhancers, etc.

Vs.

Barbara McClintock demonstrated that corn kernel color inheritance could only be explained through mobile genetic elements (aka "jumping genes")

Gene Fragments & "Pseudogenes"

An interaction map of 4,500 proteins in S. cervisiae (a yeast)

Original HGP Procedure

Transposons:

Retrotransposons:

Shotgun Sequencing

DNA sequences that code for their own replication/insertion

Transcribed into RNA and are reverse transcribed back in to DNA prior to insertion.

Code for their own Reverse Transcriptase.

Tools like microarrays make system-level analysis much easier.

Big segments (thousands of bases), present in a few copies.

Most of the Y chromosome

A small retrotransposon found in all primates.

STR's, larger repeats (up to 500 bases)

Genome Evolution

Duplication &

Divergence

Chromosomal

Alterations

Rearrangement of chromosome structures leaves signatures

Gene Families

Sequence analysis suggests that the current TPA gene resulted from transposition of exons from three different genes.

Evidence of chromosomal fusions are found in the human genome when compared to other mammalian lineages

Analysis of amino acid sequences can inform evolutionary hypotheses

Translocations during crossing over

Refers to collections of genes with identical or similar structures.

Result from duplication events.

Following duplication, sequences may diverge in structure and function.

Comparing Genomes

Identical sequence families

Non-identical sequence families

sequences of genes that occur multiple times in a genome.

usually cluster together in the genome.

example: rRNA genes (1000's of copies)

related, non-identical gene sequences.

can be found in different locations of the genome

example: alpha & beta globin genes

Looking at similarities and differences in genomes provides evidence for how evolution has changed the genetic structures of different species.

The FOXP2 gene seems to be involved in language in humans. It is related to the development of various structures in the brain.

Correlating genetic changes to fossil evidence allows for approximate dating of genetic divergence among organisms