SEX DETERMINATION.ppt sem 1 genetics

SEX DETERMINATION

INTRODUCTION

• Origin of the word "SEX"

  • Derived from Latin word "sexus" meaning separation.

  • Defined as the morphological, physiological & behavioral differences observed in egg-producing organisms vs. sperm-producing organisms.

WHAT IS SEX DETERMINATION?

• Refers to the hormonal, environmental, and genetic mechanisms that determine if an organism is male or female.

Historical Perspectives on Sex Determination

Aristotelian View (335 B.C.)

• Suggested sex determination was influenced by the male partner's heat during intercourse.

• Higher passion correlated with a greater likelihood of male offspring.

• Recommended elderly men conceive during summer for male heirs.

View by Galen (200 B.C.)

• Viewed women as poorly developed men, their genitalia being similar but inverted.

• This notion persisted for over a thousand years.

Andreas Vesalius (1543)

• Described female genitalia as internal versions of male genitalia.

1600s-1700s Perspectives

• Recognized that females produce eggs that convey parental traits.

20th Century Developments

• Environmental factors, like temperature and nutrition, were considered crucial for sex determination.

• Rediscovery of Mendel’s work and McClung’s discovery of sex chromosomes brought clarity to sex determination.

Chromosomal Correlation (1905)

• Established correlation between female sex (XX) and male sex (XY or XO) chromosomes in insects.

• Indicated nuclear components, not environmental factors, drive sexual phenotype development.

The Chromosomal Basis of Sex

• In humans and mammals, sex chromosomes include a larger X and a smaller Y chromosome.

  • The Y chromosome has homologous regions only at the ends with the X chromosome.

  • The SRY gene on the Y chromosome is crucial for developing male anatomical features.

• Males are represented as XY and females as XX.

  • Each ovum has an X chromosome, while sperm may possess either X or Y.

Sex Determination Systems

• Sex-linked genes:

  • Y-linked genes (few on Y chromosome).

  • X-linked genes on X chromosome.

Various Systems

• X-Y System (e.g. mammals)

• X-0 System (e.g. some insects)

• Z-W System (e.g. birds)

• Haplo-Diploid System (e.g. bees)

Factors Affecting Sex Determination

• Energy from metabolic pathways and hormonal controls impact sex determination mechanisms.

Mechanisms of Sex Determination

Types

• Genetically controlled

• Metabolically controlled

• Hormonally controlled

• Environmentally controlled

Genetically Controlled Mechanisms

• Sex chromosome mechanism (heterogametic)

• Genic balance mechanism

• Male haploidy (haplodiploidy)

• Single gene control of sex

Environmental Sex Determination

• In some animals, zygotes don't genetically differ in sex differentiation; instead, it's determined by environmental factors.

  • Example: Bonellia viridis larvae; attachment to female worms leads to male development.

Temperature-dependent Sex Determination

• Critical embryonic development period determines if an egg develops as male or female in reptiles.

  • No heteromorphic sex chromosomes and minimal genetic predisposition related to temperature.

In some species, such as the green sea turtle, warmer temperatures during incubation result in a higher ratio of female offspring, while cooler temperatures favor male development.

This phenomenon highlights the sensitivity of sex determination to environmental conditions, emphasizing the role of temperature as a crucial factor in reproductive strategies among reptiles.

Additionally, this temperature-dependent sex determination (TSD) system showcases the evolutionary adaptations of reptiles to their habitats, where climate fluctuations can significantly influence population dynamics.

Thermal Sensitivity and Sex Ratios

• Sex ratios in turtles and crocodilians can shift based on slight temperature variations (1.5 - 2 °C can lead to all males or all females).

• In the case of crocodilians, when eggs are incubated in a controlled laboratory setting at a constant temperature, it is expected to produce an overall sex ratio of approximately 1:1, highlighting the importance of environmental conditions in natural settings.

INCUBATION TEMPERATURE

IN turtle alligators and crocodiles

incubation temp for eggs : high 30-35 degree celcius

low : 23-28degree celcius

Nesting Behavior by Females

• Females select nest environments based on climate to influence sex ratios in their offspring.

• This behavior is crucial as warmer nests typically produce more females, while cooler nests tend to yield more males, thereby allowing mothers to optimize the sex ratio according to environmental conditions.

Genic Balance Theory (Calvin Bridges, 1926)

• Proposes sex is determined by the ratio of X-chromosomes to the number of autosome sets.

• autosomes come in pairs and contain genes that determine various traits, except for those specifically related to sexual characteristics. Humans have 22 pairs of autosomes and one pair of sex chromosomes (XX for females and XY for males). Autosomes are crucial for inheritance patterns and genetic variability.

• This theory suggests that an increased number of X-chromosomes relative to autosomes will result in female development, while a lower ratio will lead to male development, thus highlighting the importance of chromosomal composition in determining sex.

• In Drosophila, x-chromosomes carry more genes for femaleness, while autosomes carry more genes for maleness.

Sex Determination in Drosophila melanogaster

• D. melanogaster has 8 chromosomes (3 pairs of autosomes + 1 pair of sex chromosomes).

• In this species, the ratio of X chromosomes to the number of sets of autosomes is crucial; specifically, a ratio of 1.0 (two X chromosomes to two sets of autosomes) results in female flies, whereas a ratio of 0.5 (one X chromosome to two sets of autosomes) leads to male flies. This demonstrates the critical role of genetic balance in determining sexual phenotypes.

• Genic balance system: X:A ratio determines sex.

  • XX and XXY are female; XY and XO are male.

  • Statistical relationship between X-chromosomes and autosome sets influences sexual morphology.

Molecular Mechanism of Sex Determination in Drosophila

1. Establishment of X:A ratio.

2. Conversion of X:A ratio into molecular signals.

3. Differential activation of Sxl gene.

4. Differential regulation of transformer gene.

5. Action of Dsx - the switch gene for sexual determination.

6. Production of male or female phenotype.

Steps in the X:A Ratio Establishment

• Interaction of X-linked genes and autosomal proteins influences sex development pathways.

• The presence of particular proteins dictates whether the embryo follows a male or female pathway.

  MECHANISM OF SXL SPLICING

• in male the m rna is spliced in a manner that yeilds 8 exons and termination of exon occurs at no 3

• in female rna processing yeilds only 7 exons and male specific exon 3 is spliced out as large intron 3

Differential Regulation and Action of Genes

• Sxl gene acts as a master regulator in XX embryos, leading to female traits, whereas XY embryos follow a male pathway based on Sxl absence.

• Dsx gene produces different proteins through alternative splicing, affecting male/female pathways further.

• In addition, the interplay of the Transformer (tra) gene is crucial, as it is activated by the Sxl gene in females, promoting female-specific splicing of the Dsx gene, while in males, the absence of Sxl leads to default male splicing.

Human Sex Determination

Chromosomal Mechanism

• Males develop from Y sperm and X ovum while females from X sperm and X ovum.

Anatomy of the Y Chromosome

• Comprises pseudoautosomal regions, genes related to sperm development, and the SRY gene for male sex determination, accounting for 95% of its total length.

Molecular Mechanism

• Early embryo is neutral for about 2 weeks, followed by a sexual differentiation towards male or female based on the SRY gene.

Testis Pathway

• SRY codes for SOX9 inducing testis development.

• Effects of SOX9 and FGF9 result in the formation of Sertoli and Leydig cells, leading to male characteristics.

Ovarian Pathway

• In absence of SRY expression, the gonad develops into an ovary, driven by follicle and theca cells producing estrogen.

Secondary Sex Determination in Mammals

• Involves hormonal influences post-gonadal differentiation leading to classic male and female characteristics.

• The hormonal environment, including the presence of estrogen and progesterone, promotes the development of female secondary sexual characteristics such as breast development and the regulation of the menstrual cycle.

• Conversely, in males, testosterone produced by Leydig cells leads to the development of male secondary sexual characteristics, including facial hair, deepening of the voice, and increased muscle mass.

Temporal Phases

• Two main phases governing development depend on hormonal signals from differentiating gonads.

• Indifferent Stage: During early embryonic development, both male and female reproductive structures are present, but not yet differentiated.

• Differentiation Phase: Following the activation of specific genes, such as SRY in males, the gonads develop into either testes or ovaries, leading to the subsequent production of sex-specific hormones that drive the development of secondary sexual characteristics.

Dosage Compensation

• Mechanism to equilibrate gene expression between sexes.

• In Drosophila, the MSL complex regulates male-specific gene activity to balance expression across sex-linked genes.

X-Inactivation Process

• In females, one X chromosome is randomly inactivated to result in dosage compensation.

  • The Barr body is the inactive X chromosome; Xist gene is crucial for initiation of inactivation.

Random Inactivation

• X-inactivation occurs ~2 weeks post-fertilization, leading to mosaic individuals in females.

  • Both X chromosomes initially active, but one becomes inactive through Xist RNA engagement.

X Inactivation Steps

1. Choice: Assess the number of X chromosomes and select one to remain active.

2. The chosen X chromosome is maintained in an active state while the other is silenced through a series of epigenetic modifications, including methylation and histone modification.

3. Initiation: Xist coats the X chromosome designated for inactivation.

4. Spread: Propagates bi-directionally leading to silencing of the genes on the inactive chromosome.

Biological Impact of X Inactivation

• Important for balanced expression levels of X-linked genes; failure to properly inactivate can lead to disorders.

• Skewed inactivation can affect phenotypic expression in females heterozygous for X-linked traits.