Male and female sex determination

Question 1

first step in evolution of heteromorphic sex chromosomes

Answer 1

acquisition of a sex-determining locus on a proto-sex chromosome ex. male determining gene

Question 2

emeergence of seperate sexes and sex chromosomes from a hermaphrodite ancestor requires

Answer 2

male and female sterility mutation to occur on the proto-sex chromosomes

Question 3

accumulation of sexually antagonistic mutations close to the sex determining region select for

Answer 3

suppression of recombination on the proto-sex chromosomes, which can be achieved by chromosomal inversion

Question 4

the non-recombining region can increase if

Answer 4

other mutations with sex-specific fitness effects accumulation on proto-sex chormomes

a lack of recombination results in the accumulation of loss-of-function mutations at Y-linked genes (pseuedorganization)

Question 5

lack of recombination also results in

Answer 5

accumulation of repetitive dna- which can lead to an increase of the size of the evolving Y chromosome

Question 6

Large segments of non-functional DNA can be

Answer 6

deleted in old Y chromosomes and can reduce their physical size

evolutionary outcome: heteromorphic sex chromosomes, in which the X chromsome largely resembels the autosome from it derived
and the y chromosme has lost most of its ancesterol genes and may instead have accumulated repetitive dna

Question 7

pseudoautosomal region

Answer 7

2.6Mb region

tip of short arm of x and y chromosome

Question 8

Human Y chromosome

Answer 8

NRY=MSY= male specific region Y

great bulk genetically inert but many of its genes show tests-specific expression

Question 9

DAZ-

DAZL-

Answer 9

DAZ- delted in azoospermia

DAZL- deleted in azoospermia-like

Question 10

AZFa-c

Answer 10

genes involved in spermatogenesis

Question 11

high ratio of intrachromosomal similiary is due to

Answer 11

gene conversions

Question 12

Gene conversion

Answer 12

is a nonreciprocal transfer of genetic information

dontates part of its genetic info

Question 13

DNA crossover

Answer 13

two DNAs exchange part of their genetic information

Question 14

mechanisms of gene conversion

Answer 14

interallelic gene conversion

Interlocus gene conversion

Question 15

interallelic gene conversion

Answer 15

donor sequence is not altered but the acceptor sequence is altered by incorporating sequence copied from the donor sequence

Question 16

interlocus gene conversion

Answer 16

facilitated by a high degree of sequence homology between nonallelic sequences, as in the case of tandom repeats

Question 17

how a Y chromosome repairs itself

Answer 17

a gene component is injured by mutation

the mutation is corrected by copying from near-identical partner on opposite arm of a palindrome

Question 18

Sertoli cells

Answer 18

AMH- anti-muller hormone

inhibition of female sex differentiation

Question 19

Leydig cells

Answer 19

testosterone

induction of male sexual differentiation

Question 20

mechanism of sex reversion

Answer 20

illegitimate recombination effect in crossing over of meosis

plane is shifted by improper pairing

Question 21

46 XX male

Answer 21

SRY was transferred to X chromsome

cause: abnormal crossing over during male gametogenesis (meiosis I)

male infertile

Question 22

46 XY female

Answer 22

SRY is lost from Y chromosome
cause: abnormal crossing over during male gametogenesis (meiosis I)

female infertile

Question 23

but what is SRY

Answer 23

transcription factor which binds to DNA and then bends it

binds to HMG domain

Question 24

SRY protein structure and function

Answer 24

Motif highly conservative in evolution
When the protein recognizes the proper motif, after binding, bending will be the result
Functional point of view: two relatively distant genes can be regulated by the same factor
Mouse motif– involved/associated with the male type of behavior

Question 25

structure of SRY and SOX 9 proteins

Answer 25

SRY is part of the SOX protiens
Mutual feature: two nuclear localization signals
C and N terminus
Normally transcription factor has only one localization signal, and one export signal

SOX = SRY-like HMG box

Question 26

how is sry involved in RnA

Answer 26

involved in splicing
maturation of certain mRNAs

fate of products can be different

Question 27

SRY binding to B-catenin

Answer 27

inhibits Wnt signaling regulation of ovarian genes

also interacts with KRAB-O bridging molecule and recruits the KAP1-HP! gene repressor complex to the vinicity and represses its target genes

Question 28

SRY binding to SF1 or SP1

Answer 28

activate sex-determining genes such as SOX9

Question 29

SRY binding to PARP1

Answer 29

polymerizes ADP-ribose onto chromatin proteins and regulates teh accessibility of transcription factors to its target genes

Question 30

SRY and SOX9

Answer 30

bind to the same target genes and regulate their expression

Question 31

circular SRY transcript

Answer 31

cannot be translated
a product which can temporarily block/inactivate
has some splicing ability- loop seperated from stalk
can be lineralized and translated

Question 32

when two X chromosomes are present

Answer 32

RSPO1 R-spondin 1 blocks the SOX9 overstimulation in females – so no testicular differentiation

Question 33

RSPO1 LOF

Answer 33

female to male sex conversion
XX true hermaphroditism
palmoplanter hyperkeratosis
predisposition to skin squamous cell carcinoma

Question 34

RSPO2+3 GOF

Answer 34

apc-negative colon cancers

Question 35

RSPO4 LOF

Answer 35

anonychia/hyponychia

Question 36

female sex determination

Answer 36

RSPO1 binds to WNT4 which inhibits sox9 so ESTROGEN

female differentiation

Question 37

Genital ridge formation

Answer 37

4 weeks

Question 38

sex determination

Answer 38

6 weeks

Question 39

sex differentiation

Answer 39

8 weeks onwards

Question 40

overview of mammalian sex determination

Answer 40

Sex determination involves the differentiation of the bipotential embryonic gonads into the male testes or the female ovaries. Before sex determination, the bipotential gonad contains somatic cells that can give rise to either male Sertoli cells or female follicle cells, as well as testicular Leydig cells (male) or ovarian thecal cells (female) that are responsible for the production of steroid sex hormones. At this stage, WT1 and SF1 are expressed in the bipotential gonads of both sexes

male sex determination is initiated by the Y chromosome-encoded SRY gene, leading to the formation of a testis and subsequent differentiation to the male sexual phenotype. SRY is thought to initiate a genetic cascade resulting in testis differentiation. SOX9 is expressed within the Sertoli cells immediately following the expression of SRY, suggesting that SOX9 is a downstream target of SRY [4]. Recently, clinical mutations in the RSPO1 (R-spondin1: a novel class of soluble activator for Wnt/β-catenin signaling) gene were detected in XX female-to-male sex-reversed patients [71]. Taken together with transgenic mouse studies, RSPO1 was postulated subsequently to suppress the male pathway in the absence of SRY, by positively regulating the Wnt4-signalling pathway that is crucial for female development 72and73.