Chromosome Theory of Inheritance, Sex Determination, and Sex Chromosome Linkage

Chromosome Theory of Inheritance

Introduction

The chromosome theory of inheritance integrates Mendelian genetics with cytology, explaining how genes are carried on chromosomes and transmitted through generations. This theory was developed through the work of scientists such as Walter Sutton and Theodor Boveri.

• Chromosomes are the carriers of genetic information.

• Each organism has two copies of each chromosome (one from each parent).

• Homologous chromosomes separate during gamete formation (meiosis).

• Fertilization restores the diploid chromosome number.

Historical Experiments

• Walter Sutton (1903) studied meiosis in grasshoppers, showing that sex is determined by a specific chromosome pair (X and Y).

• Chromosome complement remains unchanged during transmission to progeny.

• Maternal and paternal chromosomes segregate independently.

Sex Determination

Sex Chromosomes and Autosomes

Sex chromosomes (X and Y) differ from autosomes and are responsible for determining the sex of an organism.

• In grasshoppers, males have XY and females have XX.

• In humans, females are XX and males are XY.

• Children inherit an X chromosome from their mother and either an X or Y from their father, resulting in a 1:1 sex ratio.

SRY Gene and Maleness

The SRY (Sex-determining Region of Y) gene is the primary determinant of maleness in humans.

• SRY is present and functional in normal XY males.

• SRY is absent or nonfunctional in sex-reversed individuals (XX males or XY females).

Pseudoautosomal Regions (PARs)

PARs are regions present on both X and Y chromosomes, allowing pairing during meiosis.

• PAR1 and PAR2 contain genes shared between X and Y.

• MSY region on Y contains SRY and male fertility genes.

Sex Determination in Different Species

Mechanisms of sex determination vary among species.

• Heterogametic sex: Produces two types of gametes (e.g., XY males in humans, ZW females in birds).

• Homogametic sex: Produces one type of gamete (e.g., XX females in humans, ZZ males in birds).

• Some species use environmental cues (e.g., temperature in reptiles) for sex determination.

Species	Female	Male
Humans & Drosophila	XX	XY
Birds & Butterflies	ZW	ZZ
Bees & Wasps	Diploid	Haploid
Lizards & Alligators	Cool temp.	Warm temp.
Tortoises & Turtles	Warm temp.	Cool temp.
Anemone Fish	Older adults	Young adults

Gametogenesis

Germ Line and Gametogenesis

Germ line cells are specialized diploid cells set aside during embryogenesis for gamete formation.

• Gametogenesis involves meiosis and specialized events before and after meiosis.

• Oogenesis in humans produces one ovum per primary oocyte.

• Spermatogenesis in humans produces four sperm per primary spermatocyte.

Oogenesis in Humans

• Oogonia divide by mitosis to become primary oocytes, which arrest in diplotene of prophase I.

• Meiosis I produces a large secondary oocyte and a small first polar body.

• At ovulation, one primary oocyte resumes meiosis.

• Meiosis II is completed at fertilization, producing a mature ovum and second polar body.

Sex Linkage

Genes on Sex Chromosomes

Sex linkage refers to genes located on sex chromosomes, often leading to unique inheritance patterns.

• Early geneticists used microscopy to correlate traits with chromosome presence.

• T.H. Morgan used Drosophila melanogaster to study sex-linked inheritance.

Nomenclature in Drosophila Genetics

• Gene symbols are named for mutant phenotypes (e.g., w for white eyes).

• Recessive alleles use lowercase (e.g., w), wild-type alleles use superscript plus (w+).

• Dominant alleles use uppercase (e.g., Bar for Bar eyes).

X-Linked Inheritance Patterns

The white gene in Drosophila is X-linked, leading to crisscross inheritance:

• Daughters inherit the phenotype of their fathers; sons inherit the phenotype of their mothers.

• Males are hemizygous for X-linked genes (only one allele present).

Experimental Evidence

• Morgan's crosses showed X-linked inheritance of eye color.

• Rare mistakes in meiosis (nondisjunction) produced unusual sex chromosome complements, confirming the chromosome theory.

Dosage Compensation

Definition and Mechanism

Dosage compensation ensures equal expression of X-linked genes in males and females.

• Human females have two X chromosomes; males have one.

• One X chromosome in females is randomly inactivated, forming a Barr body.

• This prevents double gene dosage in females.

Consequences of X- and Y-Chromosome Abnormalities

Chromosome Constitution	Individual	Expected Number of Barr Bodies
46,XX	Normal female	1
46,XY	Normal male	0
45,X	Turner syndrome	0
47,XXX	Triplo-X	2
47,XXY	Klinefelter syndrome	1
48,XXXY	Klinefelter syndrome	2
47,XYY	XYY syndrome	0

X-Inactivation and Mosaicism

• In female mammals, X-inactivation creates a patchwork of cells expressing different X chromosomes.

• Calico cats are a classic example of X-linked mosaicism.

• X-inactivation allows survival of individuals with extra X chromosomes.

Summary Table: Sex Determination in Drosophila and Humans

Complement	Drosophila	Humans
XXX	Dies	Nearly normal female
XX	Normal female	Normal female
XO	Sterile male	Turner female (sterile)
XY	Normal male	Normal male
XXY	Normal female	Klinefelter male (sterile)
OY	Dies	Dies

Key Terms and Concepts

• Chromosome theory of inheritance: Genes are located on chromosomes.

• Sex chromosomes: X and Y chromosomes determine sex.

• SRY gene: Determines maleness in humans.

• Dosage compensation: Mechanism to balance X-linked gene expression.

• Barr body: Inactive X chromosome in female cells.

• Hemizygosity: Possession of a single allele for a gene in males (X-linked genes).

• Nondisjunction: Error in chromosome segregation during meiosis.

Example: Drosophila White Gene Inheritance

• Cross between white-eyed male (w) and red-eyed female (w+): All F1 progeny are red-eyed.

• F2 generation shows crisscross inheritance: Daughters inherit father's phenotype, sons inherit mother's phenotype.

• Ratio in F2: 3 red-eyed : 1 white-eyed.

Additional info:

• Dosage compensation in Drosophila is achieved by upregulating the single X chromosome in males, rather than inactivating one X in females.

• Sex determination mechanisms are diverse and can involve genetic, environmental, or social factors depending on the species.