遗传 进化与生态学 5 - Genomes

本期的内容是基因组。本文集的这一部分是遗传、进化与生态学 Genetics, Evolution, and Ecology. 这门课理论上建议在阅读完文集的第一部分的内容之后再开始学习,但基础不足的朋友也可以尝试阅读喔~
这一部分的主要内容均来自 Prof. Angela J. Roles 的课程,因此本文集的这一部分均不会标记为原创。但由于文本来源不清晰,UP主还是一个字一个字码出来的文章,本文禁止非授权的转载,谢谢!
Lesson 5: Genomes
[1] Genomes
Information storage: Genomes
▸Cells contain the information to create replicas of themselves
- Replication occurs via processes such as mitosis, meiosis, and binary fission.
- Information is contained in a genome that is inherited by daughter cells.
▸Lesson topic: How is that genetic information stored and organized?
Information storage, transmission, and expression
▸Cell replication requires storage and transmission of the info needed to be a cell
- Information to make an RNA molecule is stored in nucleic acids (e.g., DNA), organized in units labeled genes. - Note: some viruses store their information only in RNA molecules rather than as a DNA molecule.
- Information is transmitted to offspring through reproduction.
▸Cell metabolism requires expression of the stored information to create functional protein or RNAs.
- Gene expression = the process of transcribing DNA into RNA and translating RNA into proteins;
- Some RNA molecules are functional and are not translated into protein (e.g., ribosomal RNAs).
[2] Structural diversity of genomes
▸Bacteria, Archaea, and Eukarya
- Information stored in double-stranded DNA (dsDNA) arranged in linear or circular molecules;
- DNA packaged with proteins and super-coiled
▸Viruses:
- Genomes consist of nucleic acids (RNA or DNA);
- Circular or linear;
- May be single- or double-stranded (or some of each: Hepadnaviridae, including hepatitis B).
▸Bacteria and Archaea:
- Genome may consist of one or more circular or linear DNA molecules;
- May contain additional genes carried on smaller circular (or linear) plasmids in addition to standard genomic material
▸Eukarya:
- Genome in membrane-bound nucleus;
- Nuclear genome composed of 2 or more linear DNA molecules;
- Organelles may have their own circular or linear DNA genomes
▸For more info and detail on genome structure in eukaryotes and prokaryotes: https://www.ncbi.nlm.nih.gov/books/NBK21120/ (Chapter 2 of the text Genomes)
[3] Prokarya
Prokaryotic genome structure
▸Prokaryotes may have circular and/or linear chromosomes
▸Borrelia burgdorferi (causes Lyme disease) has 1 main linear chromosome plus 9 circular plasmids and 12 linear plasmids.
▸Vibrio cholerae (causes cholera) has 2 circular chromsomes

▸Nucleoid = region of cell where main chromosome is resides
▸The genomic material is attached to the plasma membrane;
▸the DNA forms looped domains;
▸DNA-binding proteins (and other proteins) contribute to packaging of the DNA into a super-coiled state
- Archaean super-coiling proteins resemble those of eukaryotes rather than bacteria.


[4] Eukarya
Eukaryotes: Membrane-bound nuclei are unique to eukarya; no similar structure has been found in bacteria or archaea.

(1) Chromosome
Zooming in on chromosome structure:
▸Chromosomes consist of chromatin (DNA and proteins).
▸Chromatids are super-condensed chromosomes
- dsDNA wraps around histone proteins to form nucleosomes.
- Nucleosomes are coiled up into solenoids (30-nm fiber).
- After more coiling, you have the familiar chromatid structure.

(2) Chromatin

▸Chromosomal structure is part of gene regulation (telling cells which genes to turn on/off for making proteins)
- Heterochromatin: highly condensed, not very accessible for transcription
- Euchromatin: loosely condensed, more accessible for transcription
- State changes in response to cellular signals or gene activity
▸Molecules added to N-terminal tails of histones act as signals
- Methyl groups repress expression (reduce amount of mRNA produced)
- Acetyl groups enhance expression (increase amount of mRNA produced)
Spatial organization of chromatin

Nucleus of a chicken cell, with chromosomes stained using spectral karyotyping (“chromosome painting”). You can see exclusive chromosome territories but homologous chromosomes (e.g., both “1”) in different locations.
Eukaryotic chromosomes


▸DNA has been highly replicated
▸Chromatin highly condensed

▸Pair of sister chromatids = one replicated chromosome
▸Centromere: DNA-protein complex that binds sister chromatids together; important in moving chromosomes during mitosis and meiosis
Activity
Pause to draw and describe each of the following structures. What is the ploidy of each? How many copies of the chromosome are present?
1. One chromatid: One copy of a single set of genes (haploid)

2. A replicated chromosome: Two copies of a single set of genes (haploid)

3. A pair of homologous chromosomes: Two chromosomes with the same set of genes (diploid)

4. A pair of replicated homologous chromosomes: Two copies of two chromosomes with the same set of genes (diploid)

5. A pair of sister chromatids: Two copies of a single set of genes (haploid; same as 2)

6. Two non-homologous chromosomes: Two different chromosomes, encoding different sets of genes (different chromosomes shown by color, position of centromere, size, etc)

(3) Notation
Distinguishing chromosomes
A pair of homologous chromosomes is diploid, with one copy of each chromatid.

Why are there two of them? Where do they come from?
▸Notice how chromosomes carrying different sets of genes (heterologous chromosomes) are distinguished from each other --- usually having different sizes or centromere positions.

▸Notice how the two chromosomes that form a homologous pair are differentiated, usually by color, to allow us to distinguish between maternally and paternally inherited chromosomes.

(4) Karyotypes
To make a karyotype:
1. Collect sample of cells, induce mitosis;
2. Arrest cell division at metaphase (with colchicine);
3. Lyse the cells;
4. Fix and stain the cells to reveal chromosome banding patterns;
5. Visually pair homologous chromosomes by banding pattern.

Karyotypes and types of chromosomes
▸What are somatic chromosomes (or autosomes)?
▸What are sex chromosomes?
▸What is aneuploidy?
▸What is polyploidy?

(5) Genome Sizes
Diversity in chromosome numbers
Species vary widely in the number of chromosomes in their genome.

▸What could cause this kind of diversity?
▸Could there be benefits to have more or fewer chromsomes?
▸Or could the variation be neutral, not helping or hurting the organism?
Condensed eukaryotic chromosomes
Spectral karyotyping: Fluorescently-labeled DNA probes specific to each chromosome are hybridized to a sample of DNA.

Allows for easy detection of structural abnormalities for diagnosing disease (such as a chromosome fragment detached from its original location).