1042SCG Genetics & Evolutionary Biology Semester Summary Griffith University, Nathan Campus

Semester 1, 2014

Topics include: - Mendelian Genetics - Eukaryotic & Prokaryotic Genes - Sex Chromosomes - Variations in Chromosome Number - Pedigrees - Chromosome Structure - DNA Replication, Transcription & Translation - Molecular Basis of DNA Mutation - DNA Repair Mechanisms & Recombination - Recombinant DNA Technology - Population Genetics - Microevolution - Evolution & Natural Selection - Adaption - Species and Speciation - Phylogenetics

Mendelian Principles of Inheritance Mendel laid groundwork for the modern field of genetics

- Bred pea plants and examined their physical appearance (phenotype) o Heritable traits studied included:

Seed colour/shape Pod colour/shape Flower colour/position Stem length

- Each of these traits were visible distinct and occurred with only two phenotypes

The First Experiment (monohybrid cross) Parental (P) generation

- Two true-breeding plants (homozygous) of different phenotypes were crossed o One with dominant allele, the other with recessive allele o PP x pp (monohybrid cross)

First filial (F1) generation - Offspring showed phenotype of dominant plant

o Pp , Pp (heterozygous) Second filial (F2) generation

- 75% showed dominant phenotype (PP , Pp , Pp) - 25% showed recessive phenotype (Pp)

Conclusions reached:

1. Principle of Segregation Each individual diploid organism possesses two alleles for any given characteristic, one inherited

from their maternal parent and the other from their paternal parent. These two alleles segregate in equal proportions when gametes are formed.

2. Concept of Dominance When two different alleles are present in a genotype, only the dominant trait will be observed in

the phenotype.

Genes= an inherited factor (region of DNA) that helps determine a characteristic - Eg. gene for hair colour

Alleles= One of two or more alternative forms of a gene - Eg. allele for brown, red, blonde hair

The Second Experiment (dihybrid cross) Dihybrid cross allowed Mendel to follow two characteristics (eg. seed colour and shape)

Conclusions reached:

3. Principle of Independent assortment Alleles at different loci segregate independently of one another

Summing up, Mendel’s research led him to formulate three principles of inheritance:

1. The Principle of Segregation o Each organism has two alleles for each gene, one from each parent. These separate during meiosis

when gametes are formed so that each gamete contains one allele of each gene. Punnett squares are used to predict probability of genotypes/phenotypes

2. The Principle of Independent Assortment o Alleles at different loci segregate independently when gametes are formed during meiosis.

P allele does not affect R allele 3. The Concept of Dominance

o Phenotypes depend on the inheritance of alleles coding for dominant and recessive traits. Only one copy needed for a dominant trait to be expressed whereas two copies are needed for a recessive trait to be expressed.

Autosomes and Sex Chromosomes Autosomes= any chromosome not considered a sex chromosome Sex chromosomes= type of chromosome involved in sex determination

Chromosome number An even multiple of a basic number (types of chromosome) For humans- basic number is 23 (22 pairs of autosomal and 1 pair of sex

chromosomes), therefore chromosome number is 46 o Somatic cells- diploid genome (2n=46) o Sperm and oocytes- haploid genome (2=23)

Segregation and Independent Assortment Disjunction=separation of chromosomes toward opposite poles of the cell during cell division Normal disjunction during meiosis is responsible for segregation and independent assortment of alleles

Eukaryotic/Prokaryotic Genes Definition of a gene- unit of function that controls the synthesis of at least one polypeptide chain (protein) or RNA molecule

Prokaryotic genes - Code for only one protein

Eukaryotic genes - Code for many proteins (up to 20-30) - Mixture of coding (exons) and non-coding regions (introns)→splicing - Some genes don't produce protein- instead they code for ribosomal RNA and transfer RNA

Sex Chromosomes Mendel observed and described how alleles could segregate and independently assort from each other, however, subsequent studies found exceptions to Mendel’s predictions, often these were sex-linked.

- ie. Some traits are not inherited in Mendelian fashion

How is sex/gender defined? From a genetics point of view, by the size of the gametes:

- Female= larger gametes (ova) - Male= smaller gametes (sperm)

How is it determined? For insects (as shown with Drosophila flies) Female=XX and male=XO

- 100% of female gametes have X chromosome - 50% of male gametes have X chromosome and 50% have O chromosome

Sex is determined by number of X chromosomes (ratio of sex chromosome to autosomes) - X:A=1 - female - X:A=0.5 - male - 0.5<X:A<1- hermaphrodite

Gender Sex chromosomes Autosomes X:A

F XX AA 1:1

M XY AA 0.5:1

M XO AA 0.5:1

F XXY AA 1:1

For mammals Female=XX and male=XY

- 100% of female gametes have X chromosome (homogametic) - 50% of male gametes have X chromosome and 50% have Y chromosome (heterogametic)

Sex is determined by presence/absence of a Y chromosome

Genotype Phenotype

XO Turner syndrome Female

XXY,XXXY Klinefelters syndrome Male

XXX Poly-X Female

Conclusions

1. X chromosomes are required for healthy development in both genders 2. Male determining gene is on Y chromosome and is dominant (SRY) 3. Absence of Y chromosome will result in female phenotype

Abnormalities in sex chromosome numbers Klinefelter Syndrome (XXY or XXXY or XXYY)

- 1:1000 births effected - 1 or more Y chromosomes and multiple X chromosomes

o Male o Reduced facial and pubic hair o Small testes o Taller than normal o Sterile o Normal intelligence

Turners Syndrome (XO) - 1:3000 female births - Absence of a sex chromosome

o Underdeveloped secondary sex characteristics o Short o Low hairline o Broad chest o Folds of skin on neck o Normal intelligence

Sex Determination Sex is determined by dominant effect of the Y chromosome

- Presence of Y= male - Absence of Y= female

TDF (testis determination factor), a gene on the Y chromosome in the SRY region (sex-determining-region-Y) - XX which have male phenotype carry SRY gene - XY which have female phenotype are missing SRY gene

XYSRY→(SRY turns on other genes)→TDF→development of testes→testosterone→androgen receptor

- Testosterone interacts with cell which have androgen receptors

Androgen Insensitivity Syndrome (Testicular Feminization) No androgen receptors on cell surface

- After testes have formed, testosterone is secreted and initiates development of male sexual characteristics

- Testosterone binds to the testosterone receptor present on the cell surface o Transmits a signal to cell o Alters gene expression such that male development ensues

- If signalling system fails, individual develops as a female Caused by inactivating mutations in their testosterone receptor gene (Tfm)

- Testes are formed→testosterone secreted - Testosterone signal cannot be transduced (has no effect)

Dosage Compensation of X-linked Genes Since females have more X chromosomes, compensation is required to ensure normal, even protein development for males and females.

Drosophila Females (XX)- each X chromosome expressed 100% Males (XO)- X chromosome expressed 200% (hyper-activated)

Mammals Females (XX)- only one of the two X chromosomes expressed

- The other will remain inactivated Males (XY)- lone X chromosome fully expressed

X inactivation in female mammals (Mosaicism) Occurs when embryo consists of a few thousand cells Each cell makes independent decision to inactivate one of its X chromosomes (at random)

- Inactivated chromosome remains inactivated in all descendant cells - Female mammals are genetic mosaics

o Female heterozygous for an X-linked trait is able to show both phenotypes - In-active X chromosome forms Barr bodies in the mammal's somatic cells

The chromosome theory of heredity X-linked/sex-linked genes are genes located on the X chromosome

- Do not independently assort due to their physical linkage Established by experiments conducted by Thomas Morgan on drosophila

- Crosses showed that gene for eye colour was linked to the X chromosome - X and Y are morphologically distinct from each other and autosomes

Sex-linked genes in humans Sex linked mutations are easy to detect as the show up immediately in hemizygous males

- Recessive X-linked traits more commonly in males as they only need to inherit one recessive allele to show recessive phenotype

o Women have two X chromosomes, thus probability is much less

There are some homologous genes on both the X and Y chromosomes - Mostly located at ends of arms - Alleles in this region inherited in similar manner to autosomal

alleles o Region is called the pseudo-autosomal region

- Pseudo-autosomal alleges mediate pairing of X and Y chromosomes during mitosis/meiosis

Colour blindness X-linked recessive trait

- Three receptors for light in eye o Red and green are X-linked, blue is autosomal

- Rare but not impossible in females Haemophillia Blood clotting disorder

- Virtually all affected are male

Fragile X Syndrome and Mental Retardation Many cases of mental retardation appear to follow sex-linked pattern of inheritance

- Associated with cytological anomaly o Constriction near tip of long arm on X chromosome

= fragile X - Affected females- heterozygous - Affected males- hemizygous

o Some carriers are unaffected

Genes only on the Y chromosome Very few identified

- Unusual as Y-linked diseases would be expressed in all progeny of effected males H-Y antigen- male-specific cell surface antigen TDF (testis determining factor)- critical for testicular differentiation/male sexual characteristics

.