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Genetics 4BIO3 J.M.

1st SEM 2014-2015

SEX DETERMINATION AND SEX CHROMOSOMES

INTRODUCTION
Reproductive modes and life cycles on organisms:
1. Asexual no sexual reproduction
2. Alternate between short periods of sexual and long periods of
asexual reproduction
3. Diploid eukaryotes sexual reproduction is evident
Sexual reproduction produce new members of species; orderly
transmission of genetic material from parents to offspring
Phenotypic variability due to segregation and independent
assortment during meiosis

Meiosis ensures genetic constancy within species


Successful fertilization depends on sexual differentiation
Differentiation phenotypic dimorphism of males and females
Heteromorphic chromosomes (XY) dissimilar chromosomes;
characterizes 1 sex (results to label of sex chromosomes)
Sex determination effect of genes rather than chromosomes (the
genes can be present on sex chromosomes or autosomes)

1 LIFE CYCLES DEPEND ON SEXUAL DIFFERENTIATION


Primary sexual differentiation involves only gonads
Unisexual (dioecious, gonochoric) individual with only male or female
reproductive organs
Secondary sexual differentiation involves overall appearance
of the organism (differences such as mammary glands and
Bisexual (monoecious, hermaphroditic) individuals with both male and
external genitalia)
female; can produce both sperm and egg
Intersex individuals of intermediate sexual condition; usually sterile

Zea mays
Many plant life cycles alternate
between haploid gametophyte
stage and diploid sporophyte stage
- linked by meiosis and fertilization
Maize (corn) monoecious seed
plant; sporophyte phase dominate
in the life cycle
Both male and female structures are
present on the adult plant

1. Stamens (collectively constitute the tassel) produce diploid microspore mother cells
2. Microspore mother cell undergoes meiosis gives rise to 4 haploid microspores
3. Haploid microspores develop into mature male microgametophyte pollen grain (2 haploid sperm
nuclei)
4. Pistil produces diploid megaspore mother cells
5. Megaspore mother cell undergoes meiosis 1 of the 4 haploid megaspores survive
6. Haploid megaspore undergoes mitosis produces 8 haploid nuclei enclosed in embryo sac
7. 2 of the nuclei unite near the center becomes endosperm nuclei
8. 3 of the nuclei at micropyle end (where sperm enters) the oocyte and 2 synergids
9. 3 other nuclei antipodal nuclei; at the opposite end of the embryo sac
10.Pollination occurs when pollen grains make contact with stigma of the pistil

Genetics 4BIO3 J.M.


11. Develop long pollen tubes toward embryo sac
12. Contact at micropyle 2 sperm nucleus unites with 2 endosperm
nuclei (double fertilization)
13. Double fertilization results to diploid zygote nucleus, triploid
endosperm nucleus
14. Maturation into a kernel
15. Kernel can give rise to a sporophyte (new plant)

1st SEM 2014-2015

Mutant genes that disrupt normal tassel and pistil formation normal
products of the mutant genes affect the differentiation of male or
female tissues
Mutations of tassel seed produces only female structures
Mutations of silkless and barren stalk produces only malefunctioning reproductive organs

Caenorhabditis elegans
Beneficial in investigating genetic control of development
2 sexual phenotypes: males having testes only, hermaphrodites
During hermaphrodite larval development testes form producing
sperm is stored; oogenesis does not occur until adult stage is reached
Eggs produced are fertilized by stored sperm through self-fertilization
Offspring hermaphrodites (less than 1 percent are males)
Males can mate with hermaphrodites produces half male, half
hermaphrodites

Genetic signal determining maleness genes located on both X


chromosomes and autosomes
Does not have Y chromosome
Hermaphrodites 2 X chromosomes
Males 1 X chromosome
Ratio of X chromosomes to number of autosome sets determines sex
Ratio of 1.0 ( 2 X chromosomes, 2 copies of autosome) hermaphrodite
Ratio of 0.5 - male

Genetics 4BIO3 J.M.

2 X AND Y CHROMOSOMES WERE FIRST LINKED TO SEX DETERMINATION


H. Henking identified nuclear structure in sperm of certain insects (labelled the X-body)
Clarence McClung showed sperm in grasshoppers contain unusual genetic structure
(heterochromosome)
Edmund B. Wilson
Demonstrated that butterfly Protenor female somatic cells have 14 chromosomes (with 2 X
chromosomes); male somatic cells have 13 chromosomes (1 X chromosome)
Fertilization by X-bearing sperm results in female offspring
Fertilization by X-deficient sperm results in male offspring
Milkweed bug Lygaeus turcicus both sexes have 14 chromosomes (12 autosomes)
Females have 2 Xchromsomes
Male have 1 X chromosome, smaller heterochromosome labelled as Y chromosome
Protenor (XX/XO) mode of sex determination
Presence or absence of X chromosome in male produces a 1:1 Sex ratio in offspring
Depends on random distribution of X chromosome into half of the male gametes during
segregation
Lygaeus (XX/XY) mode of sex determination
Females produce gametes of (6A + X)
Males produce (6A + X) and (6A + Y)
Equal numbers of male and female progeny will be produced with distinct chromosome
complements
Heterogametic sex unlike gametes; gametes determine sex of the progeny
Homogametic sex uniform gametes with regard to chromosome numbers and types
ZZ/ZW female is heterogametic (ZW)

1st SEM 2014-2015

Genetics 4BIO3 J.M.

1st SEM 2014-2015

3 THE Y CHROMOSOME DETERMINES MALENESS IN HUMANS


Joe Hin Tjio and Albert Levan
Effective way to prepare chromosomes for viewing
Clear demonstration of metaphase stages human diploid number is
46

C.E. Ford and John L. Hamerton male karyotype illustrates difference in


size between human X and Y chromosomes
2 chromosomes X and Y sex chromosomes
Female 2 X chromosomes; Male have X and Y chromosome

Klinefelter and Turner Syndromes


Klinefelter Syndrome (47, XXY)
Generally tall and have long arms, legs, hands, and feet
Have male internal ducts and genitalia
Testes are rudimentary does not produce sperm
Feminine sexual development is not entirely expressed
Slight enlargement of breast (gynecomastia), rounded hips
Intelligence is often below the normal range
47 chromosomes 44 autosomes, 3 sex chromosomes
Nondisjunction failure of sex chromosomes to segregate properly
Presence of Y chromosomes determines maleness
Occurs 1 of every 660 male births
Similar with 48,XXXY, 48,XXYY, 49, XXXXY, and 49,XXXYY

Turner Syndrome (45, X)


Female external genitalia and internal ducts
Ovaries are rudimentary
Short stature (usually under 5 ft.), skin flaps on back of neck
Undeveloped breast, broad, shieldlike chest
Normal intelligence
45 chromosomes 1 sex chromosome only
Nondisjunction failure of sex chromosomes to segregate properly
Mosaics- other karyotypes similar to 45,X mitotic error during early
development (normal karyotypes can give rise to the syndrome)
45, X/46,XY and 45,X/46,XX
Observe in 1 in 2000 female

Genetics 4BIO3 J.M.

47, XXX Syndrome


Abnormal 3 X chromosomes + normal autosomes
female differentiation
Triplo-x occurs in 1 of 1000 female births
Perfectly normal; not known unless a karyotype is done
Some may exhibit underdeveloped secondary sex
characteristics, sterility, delayed development of
language and motor skills, and mental retardation
Rare cases 48, XXXX (tetra-X) and 49, XXXXX (penta-X)
Presence of extra X disrupts development of normal
female

47, XYY Condition


Additional Y chromosome in normal male karyotype
Males with above average height, subnormal
intelligence, personality disorders, and with dangerous,
violent, or criminal propensities
High but not constant correlation between extra Y
chromosome and predisposition of males to exhibit
behavioural problems

1st SEM 2014-2015

Sexual Differentiation in Humans


Development of humans into dimorphic males and females
Early development hermaphrodite
1. 5th week of gestation gonadal primordia (forms the gonads) arise as pair of
gonadal ridges
Genital ridges; associated with embryonic kidney
Bipotential gonads can form ovary or testis
Hermaphroditic at this stage due to indistinguishable reproductive structures
2. Primordial germ cells migrate to the ridges
3. Outer cortex and inner medulla form
Cortex can be an ovary
Medulla can be a testis
4. Undifferentiated ducts (Wolffian and Mllerian ducts) exists
Wolffian ducts differentiate to male reproductive tract
Mllerian ducts differentiate to female reproductive tract
5. Presence of Y chromosome induces development of medulla into testis (7th week)
6. If no Y chromosome Cortex forms ovarian tissue, Mllerian ducts forms oviducts
Depending on pathway, other duct system degenerates

Y Chromosome and Male Development


Y chromosome has at least 75 genes; has regions homologous on X chromosomes
Pseudoautosomal regions (PARs) present on both ends, homologous with X chromosome;
pairing region is critical to segregation of X and Y chromosomes during male gametogenesis
Male-specific region of the Y (MSY) nonrecombining region of the Y (NRY); does not form
synapse or recombine with X chromosome
MSY
Euchromatic region contain functional genes
Heterochromatic region lack genes
Sex-determining region Y (SRY) critical gene controlling male sexual development; absent in
X chromosomes (it depends); becomes active in embryos during the 6th week
SRY encodes testis-determining factor (TDF), protein differentiates gonadal tissue

Genetics 4BIO3 J.M.

1st SEM 2014-2015

4 RATIO OF MALES TO FEMALES IS NOT 1.0


Presence of heteromorphic sex chromosomes in 1 sex of a species but
not in the other provides potential mechanism for producing equal
proportions of male and female offspring
Potential depends on segregation of X and Y (or Z and W) during
meiosis
Small PARs exist at both ends of human X and Y chromosomes
(suggests X and Y chromosomes synapse and then segregate)
Provided both are equally successful in fertilization and viable ratio
is 1:1 male: female offspring
Sex ratio actual proportion of male to female offspring
Primary sex ratio proportion of males to females conceived in a
population
Secondary sex ratio proportion of each sex that is born; does not
account any disproportionate embryonic or fetal mortality

Secondary sex ratio in human population not 1.0


More males are conceived than females in human population
Assumptions that were the basis of the theoretical ratio must be
examined:
1. Because of segregation, males produce equal numbers of X- and Ybearing sperm
2. Each type of sperm has equivalent viability and motility in female
reproductive tract
3. The egg surface equally receptive to both X- and Y- bearing sperm
Y chromosome smaller, less mass
Y-bearing sperm are more motile than X-bearing sperm increased
probability of male zygote

5 DOSAGE COMPENSATION PREVENTS EXCESSIVE EXPRESSION OF X-LINKED GENES


Presence of 2 X chromosomes in normal females and 1 X on males
unique compared to same numbers of autosomes present in both sexes
Disparity between chromosome number can create a genetic dosage
difference between males and females potential of females to produce
twice as much of each product of all X-linked genes

Embryonic development depends on proper timing and precise


regulated levels of gene expression or disease phenotypes may
occur
Dosage compensation genetic mechanism balancing dose of X
chromosome gene expression in females and males

Barr Bodies
Barr and Bertram
Experiments with female cats
Observed darkly staining body in interphase of nerve cells absent in
males (can be found in human female buccal mucosa or fibroblasts)
Stains positively for number of different DNA-binding dyes

Barr body
Sex chromatin body
Inactivated X chromosome provides possible mechanism for
dosage compensation; Arises from one the 2 X chromosomes
X genetic dosage will be same for male and females

Genetics 4BIO3 J.M.


In cases of multiple X only 1 is activated
In Turner 45, X no Barr body
Klinefelter 47,XXY 1 Barr body
47, XXX 2 Barr bodies
Number of Barr bodies follows an N-1 rule, where N is number of X
chromosomes present

Problems in the Barr body if only 1 X is activated why Turner 45, X or


Klinefelter 47, XXY is not normal
Possible explanation chromosome inactivation does not normally
occur in very early stages of development of the cells
All genes on each X chromosome forming a Barr body are
inactivated

Lyon Hypothesis
Mary Lyon and Liane Russell
Inactivation of X chromosomes occur randomly in somatic cells at a
point early in embryonic development (during blastocyst)
When inactivated all descendant cells have same X chromosome
inactivated as initial progenitor cell
Based on observations of female mice heterozygous for X-linked
coat color genes - 2 colors due to expression of alleles in both X
chromosome

1st SEM 2014-2015

Mechanism of Inactivation
Imprinting
DNA, attached histone proteins, or both are chemically modified
silencing most genes part of the chromosome
A memory is created keeping the same homolog inactivated
following chromosome replications and cell divisions
Genetic information is modified and gene expression is repressed
Epigenetics
Mechanism of Inactivation
Region of mammalian X chromosome major control unit (on
proximal end of p arms)
X inactivation center (Xic) genetic expression occurs only on X
chromosome that is inactivated; 1 MB (106 base pairs)
Contain putative regulatory units and 4 genes one of it is the Xinactive specific transcript (XIST); critical gene for X-inactivation

Gene expression in clones of human fibroblast cells


Synthesis of enzyme glucose-6 phosphate dehydrogenase
controlled by X-linked gene
Fibroblasts taken from females heterozygous for different allelic
forms of G6PD
Inactivation of an X chromosome occurs randomly in development
female shows 2 types of clones with 1 electrophoretic form of G6PD
in approximately equal proportions
XIST

Consequence of X-inactivation mammalian females are mosaics for all

heterozygous X-linked alleles (some areas express only maternally or


paternally derived alleles)

Ex. Red-green color blindness (X-linked recessive disorder)


Male fully blind

Female mosaic retinas, patches of defective color projection

RNA product large, does not encode protein, not translated


RNA products spread over and coat X chromosome bearing the
gene that produced them
At Xic locus, Tsix and Xite (noncoding genes) play a role in Xinactivation
Transcription occurs at low levels on all X chromosomes

Genetics 4BIO3 J.M.

1st SEM 2014-2015

6 RATIO OF X CHROMOSOMES TO AUTOSOMES DETERMINS SEX IN Drosophila


Calvin Bridges
Y chromosome in Drosophila does not cause maleness
X chromosomes and autosomes determines the sex (like in C. elegans)
2 phases of Bridges work
1. Study of offspring resulting from nondisjunction of the X chromosomes
during meiosis in females
2. Subsequent work with female progeny with 3 copies of each
chromosome (triploid, 3n, females)
First phase
Nondisjunction failure of paired chromosomes to segregate or separate
during anaphase stage of meiosis I or II
Results to 2 types of abnormal gametes:
Extra chromosome (n+1)
Lacks chromosome (n-1)
Fertilization of abnormal gametes produces (2n+1) or (2n-1) zygote
Bridges found that XXY flies were normal females, X0 were sterile males
Presence of Y (XXY) did not produce males; absence (X0) did not produce
femaleness Y lacks male-determining factors and is not essential to male
fertility
Second phase
Studied progeny of 3n females have 3 copies of each of the haploid
complement of chromosomes
3n females from rare diploid eggs fertilized by normal haploid sperm;
have heavy set bodies, coarse bristles, coarse eyes
Critical factor in sex determination ratio of X chromosomes to number
of haploid sets of autosomes (X:A)
Intersexes expressed both male and female morphology, sterile
Sex determination is by the autosomes

Genic balance theory


Presence of Y does not determine male but due to failure to
contribute an X chromosome
Threshold for maleness ratio is 1:2 (X:2A)
Presence of additional x (XX:2A) femaleness
Genes involved in sex determination
Transformer (tra) recessive autosomal gene
Sex-lethal (Sxl) master switch

Genetics 4BIO3 J.M.

7 TEMPERATURE VARIATION CONTROLS SEX DETERMINATION IN REPTILES


Temperature-dependent sex determination (TSD)
Sex is predetermined at conception by sex-chromosome composition
(snakes, lizards)
TSD crocodiles, turtles, some lizards
Sex determination achieved according to incubation temperature of
eggs during critical period of embryonic development
Case 1

Case 2

Case 3

Low temperatures 100% females


High temperatures 100% male
Low temperatures 100% male
High temperatures 100% female
Low and high temperatures 100% female
Intermediate temperatures various % of male

Observations:
1. Certain temperatures result to both male and female offspring
2. Pivotal temperature (Tp) range is fairly narrow (less than 5oC)
Involvement of steroids (estrogen) and enzymes involved in synthesis
on the effect of temperature in sex
Aromatase converts androgens (testosterone) to estrogen; activity
is correlated with pathway of reactions occurring during gonadal
differentiation

1st SEM 2014-2015