The Nature of SexThe Nature of Sex

Ricki LewisRicki Lewis

Klug and CummingsKlug and Cummings

Platypus Sex ChromosomePlatypus Sex Chromosome Platypus - EchidnaPlatypus - Echidna Earliest type of mammal duck like bill, web feet,fur, and mammary glandsEarliest type of mammal duck like bill, web feet,fur, and mammary glands The platypus, long thought a strange creature, just got stranger The platypus, long thought a strange creature, just got stranger Researchers discovered that it has 10 sex chromosomes, Researchers discovered that it has 10 sex chromosomes, Some of them linked to mammals and some to birds.Some of them linked to mammals and some to birds.

Evolution of the Sex Evolution of the Sex Chromosomes - MarsupialsChromosomes - Marsupials

http://www.pubmedcentral.nih.gov/arhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=53113&tools=ticlerender.fcgi?artid=53113&tools=botbot

httphttp://www.newscientist.com/article.ns?id://www.newscientist.com/article.ns?id=dn6568=dn6568

The Nature of Sex – The sex The Nature of Sex – The sex chromosomes in humanschromosomes in humans

The Evolution of YThe Evolution of Y The X and Y chromosomes diverged around 300 The X and Y chromosomes diverged around 300

million years ago when some reptile, the distant million years ago when some reptile, the distant ancestor of all mammals, developed a so-called ancestor of all mammals, developed a so-called 'male gene' - simply possessing this gene caused 'male gene' - simply possessing this gene caused the organism to be male. the organism to be male.

The chromosome with this gene became the Y The chromosome with this gene became the Y chromosome, and a similar chromosome without chromosome, and a similar chromosome without it became the X chromosome. it became the X chromosome.

So initially, X and Y chromosomes were nearly So initially, X and Y chromosomes were nearly identical. Over time, genes which were beneficial identical. Over time, genes which were beneficial for males and harmful to (or had no effect on) for males and harmful to (or had no effect on) females either moved to or developed on the Y females either moved to or developed on the Y chromosome.chromosome.

Recombination between X and Recombination between X and YY

RecombinationRecombination between the X and Y between the X and Y chromosomes proved harmful - it resulted in chromosomes proved harmful - it resulted in males without necessary genes formerly found on males without necessary genes formerly found on the X chromosome the X chromosome

Females were found with unnecessary or even Females were found with unnecessary or even harmful genes previously only found on the Y harmful genes previously only found on the Y chromosome. chromosome.

As a result, genes beneficial to males assembled As a result, genes beneficial to males assembled near the sex-determining genes in order to make near the sex-determining genes in order to make this less probable. Eventually, the Y chromosome this less probable. Eventually, the Y chromosome changed in such a way as to inhibit the areas changed in such a way as to inhibit the areas around the sex determining genes from around the sex determining genes from recombining at all with the X chromosome.recombining at all with the X chromosome.

The evolution of the YThe evolution of the Y With time, larger and larger areas became With time, larger and larger areas became

unable to recombine with the X chromosome. unable to recombine with the X chromosome. This caused its own problems: without This caused its own problems: without

recombination, the removal of harmful recombination, the removal of harmful mutations from chromosomes becomes mutations from chromosomes becomes increasingly difficult. increasingly difficult.

These harmful mutations continued to These harmful mutations continued to damage Y-unique genes until several finally damage Y-unique genes until several finally stopped functioning and became stopped functioning and became genetic junkgenetic junk; this was eventually removed ; this was eventually removed from the Y chromosome.from the Y chromosome.

More about the Y More about the Y chromosomechromosome

As a result of this process 95% of the As a result of this process 95% of the human Y chromosome is unable to human Y chromosome is unable to recombine, the chromosome itself recombine, the chromosome itself contains only 83 working genescontains only 83 working genes

Compare this to close to 1000 working Compare this to close to 1000 working genes on the X chromosome. genes on the X chromosome.

In some animals, Y degradation is even In some animals, Y degradation is even more severe. For example, the more severe. For example, the kangarookangaroo Y Y chromosome contains chromosome contains onlyonly the the SRYSRY gene gene

The Y chromosomeThe Y chromosome

The Y chromosome The Y chromosome has a p and q armhas a p and q arm

The SRY gene The SRY gene bestows the male bestows the male identityidentity

The The pseudoautosomal pseudoautosomal region is on the q region is on the q armarm

Y chromosomeY chromosome

Short and long armShort and long arm There are 63 pseudoautosomal There are 63 pseudoautosomal

genes that cross over with the X genes that cross over with the X chromosomechromosome

Bulk of the Y chromosome is termed Bulk of the Y chromosome is termed the male-specific region or MSYthe male-specific region or MSY

The MSY lies between the two The MSY lies between the two pseudoautosomal regionspseudoautosomal regions

MSY and Pseudoautosomal MSY and Pseudoautosomal genesgenes

The MSY lies between the two The MSY lies between the two pseudoautosomal regions and it pseudoautosomal regions and it consista of three classes of DNA consista of three classes of DNA sequencessequences

About 10 to 15 % of the MSY consists About 10 to 15 % of the MSY consists of X transposed sequences that are of X transposed sequences that are 99 percent identical to counterparts 99 percent identical to counterparts on the X chromosomeon the X chromosome

MSY and the otherMSY and the other

The remainder of the MSY contains The remainder of the MSY contains palindrome ridden regions called palindrome ridden regions called ampliconsamplicons

Most of the MSY genes are vital to Most of the MSY genes are vital to fertilityfertility

Y chromosomeY chromosome

Although 95% of the Y chromosome lies Although 95% of the Y chromosome lies between the pseudoautosomal regions, between the pseudoautosomal regions, fewer than 80 genes have been found here. fewer than 80 genes have been found here.

Over half of this region is genetically-barren Over half of this region is genetically-barren heterochromatinheterochromatin. Of the 80-odd genes found . Of the 80-odd genes found in the in the euchromatineuchromatin, some encode proteins , some encode proteins

The others encode proteins that appear to The others encode proteins that appear to function only in the testes. A key player in function only in the testes. A key player in this latter group is this latter group is SRYSRY. .

SRYSRY

The SRY encodes a transcription The SRY encodes a transcription factorfactor

It sends signals to the indifferent It sends signals to the indifferent gonads early in the development of gonads early in the development of the embryothe embryo

Genes on the Y Genes on the Y chromosomechromosome

AMELY (AMELY (amelogeninamelogenin,Y-chromosomal) ,Y-chromosomal) ANT3Y (ANT3Y (adenineadenine nucleotide translocator-3 on the Y) nucleotide translocator-3 on the Y) ASMTY (which stands for ASMTY (which stands for acetylserotoninacetylserotonin methyltransferasemethyltransferase) ) AZF1AZF1 ( (azoospermiaazoospermia factor 1) factor 1) AZF2 (azoospermia factor 2) AZF2 (azoospermia factor 2) BPY2 (basic protein on the Y chromosome) BPY2 (basic protein on the Y chromosome) CSF2RY (granulocyte-macrophage colony-stimulating factor receptor, alpha CSF2RY (granulocyte-macrophage colony-stimulating factor receptor, alpha

subunit on the Y chromosome) subunit on the Y chromosome) DAZ (deleted in azoospermia) DAZ (deleted in azoospermia) IL3RAY (IL3RAY (interleukininterleukin-3 receptor) -3 receptor) PRKY (protein kinase, Y-linked) PRKY (protein kinase, Y-linked) RBM1 (RBM1 (RNARNA binding motif protein, Y chromosome, family 1, member A1) binding motif protein, Y chromosome, family 1, member A1) RBM2 (RNA binding motif protein 2) RBM2 (RNA binding motif protein 2) SRYSRY (sex-determining region) (sex-determining region) TDF (TDF (testis determining factortestis determining factor) ) TSPY (TSPY (testistestis-specific protein) -specific protein) UTY (ubiquitously transcribed TPR gene on Y chromosome) UTY (ubiquitously transcribed TPR gene on Y chromosome) ZFY (zinc finger protein) ZFY (zinc finger protein)

Human Chromosome Human Chromosome LaunchPadLaunchPad

http://www.ornl.gov/sci/techresourcehttp://www.ornl.gov/sci/techresources/Human_Genome/launchpad/chromYs/Human_Genome/launchpad/chromY.shtml.shtml

Tracing the history of the YTracing the history of the Y indels indels - insertions into or deletions of the DNA at particular - insertions into or deletions of the DNA at particular

locations on the chromosome. One insertion particularly locations on the chromosome. One insertion particularly useful in population studies is the useful in population studies is the YAPYAP, which stands for "Y , which stands for "Y chromosome alu polymorphism." chromosome alu polymorphism." AluAlu is a sequence of is a sequence of approximately 300 letters (base pairs) which has inserted approximately 300 letters (base pairs) which has inserted itself into a particular region of the DNA. There have been itself into a particular region of the DNA. There have been some half a million alu insertions in human DNA; YAP is one some half a million alu insertions in human DNA; YAP is one of the more recent. of the more recent.

snips snips - are "single nucleotide polymorphisms" in which a - are "single nucleotide polymorphisms" in which a particular nucleotide (an A, for example) is changed particular nucleotide (an A, for example) is changed (perhaps into a G). Stable indels and snips are relatively (perhaps into a G). Stable indels and snips are relatively rare and, in the case of the latter, so infrequent that it is rare and, in the case of the latter, so infrequent that it is reasonable to assume they have occurred at any particular reasonable to assume they have occurred at any particular position in the genome only once in the course of human position in the genome only once in the course of human evolution. Snips and stable alus have been termed "unique evolution. Snips and stable alus have been termed "unique event polymorphisms" (UEPs). event polymorphisms" (UEPs).

Tracing the history of the YTracing the history of the Y

microsatellitesmicrosatellites are short sequences of are short sequences of nucleotides (such as nucleotides (such as GATAGATA) repeated ) repeated over and over again a variable number over and over again a variable number of times in tandem. The specific number of times in tandem. The specific number of repeats in a particular variant (or of repeats in a particular variant (or alleleallele) usually remains unchanged from ) usually remains unchanged from generation to generation but changes generation to generation but changes do sometimes occur and the number of do sometimes occur and the number of repeats may increase or decrease. repeats may increase or decrease.

Tracing the YTracing the Y The fourth polymorphism category is The fourth polymorphism category is

minisatellitesminisatellites, extensively studied by Mark Jobling , extensively studied by Mark Jobling at the University of Leicester. Unlike at the University of Leicester. Unlike microsatellites, in which the repeated sequences microsatellites, in which the repeated sequences are short (often no more than 3 or 4 nucleotides), are short (often no more than 3 or 4 nucleotides),

In minisatellites they are normally 10-60 base In minisatellites they are normally 10-60 base pairs long and the number of repeats often pairs long and the number of repeats often extends to several dozen. Changes during the extends to several dozen. Changes during the copying process take place more frequently in copying process take place more frequently in minisatellites than in microsatellites and the minisatellites than in microsatellites and the mechanisms may be different in the two cases. mechanisms may be different in the two cases.

The Y chromosome and the The Y chromosome and the European MenEuropean Men

http://www.raceandhistory.com/Scienhttp://www.raceandhistory.com/Science/europeanmen.htmce/europeanmen.htm

The X chromosomeThe X chromosome

Mammalian comparisonMammalian comparison

Unraveling the XUnraveling the X

X Chromosome – related X Chromosome – related genesgenes

AlportAlport syndrome syndrome Androgen insensitivity syndromeAndrogen insensitivity syndrome Becker's muscular dystrophyBecker's muscular dystrophy CentronuclearCentronuclear myopathymyopathy Charcot-Marie-Tooth diseaseCharcot-Marie-Tooth disease Coffin-Lowry syndromeCoffin-Lowry syndrome DuchenneDuchenne FabryFabry disease disease Fragile X syndromeFragile X syndrome Glucose-6-phosphate Glucose-6-phosphate dehydrogenasedehydrogenase deficiency deficiency HemophiliaHemophilia IncontinentiaIncontinentia pigmentipigmenti Lesch-NyhanLesch-Nyhan syndrome syndrome MenkesMenkes disease disease MyotubularMyotubular myopathymyopathy NonsyndromicNonsyndromic deafness deafness and X-linked nonsyndromic deafness and X-linked nonsyndromic deafness Ornithine transcarbamylase deficiency Ornithine transcarbamylase deficiency Rett syndrome Rett syndrome Spinal and bulbar muscular atrophy Spinal and bulbar muscular atrophy X-linked severe combined immunodeficiency (SCID) X-linked severe combined immunodeficiency (SCID) X-linked agammaglobulinemia (XLA) X-linked agammaglobulinemia (XLA) X-linked sideroblastic anemia X-linked sideroblastic anemia

X and Y chromosomesX and Y chromosomes

Genes on the X chromosome are Genes on the X chromosome are referred to as X linkedreferred to as X linked

Genes on the Y chromosome are Genes on the Y chromosome are referred to as Y linkedreferred to as Y linked

X inactivationX inactivation

There are two X chromosome in There are two X chromosome in femalesfemales

One is inactivated early in One is inactivated early in embryological developmentembryological development

The inactivation is random so that only The inactivation is random so that only one chromosome is active in each cellone chromosome is active in each cell

Females are mosaics of the X Females are mosaics of the X chromosomeschromosomes

Barr BodyBarr Body

The Barr Body is The Barr Body is the remnant of the the remnant of the X chromosomeX chromosome

Calico CatsCalico Cats

Sex LimitedSex Limited

Genes that are only expressed in one Genes that are only expressed in one sexsex

Antlers in male deerAntlers in male deer Milk production in female cowsMilk production in female cows

Sex influencedSex influenced

Baldness in malesBaldness in males Traits that are expressed with one Traits that are expressed with one

copy in males and two copies in copy in males and two copies in females( with hormonal influence)females( with hormonal influence)

Genomic imprintingGenomic imprinting The phenomenon of genomic imprinting is the The phenomenon of genomic imprinting is the

differential modification of the maternal and differential modification of the maternal and paternal genetic contributions to the zygote, paternal genetic contributions to the zygote, resulting in the differential expression of parental resulting in the differential expression of parental alleles during development and in the adult. alleles during development and in the adult.

A disturbance in genomic imprinting in humans A disturbance in genomic imprinting in humans has been shown to play a role in several birth has been shown to play a role in several birth defects, genetic diseases and cancers. defects, genetic diseases and cancers.

In humans, the most convincing demonstration of In humans, the most convincing demonstration of an imprinted region is at chromosome 15q11-q13 an imprinted region is at chromosome 15q11-q13 with a deficiency of the maternal region resulting with a deficiency of the maternal region resulting in the Angelman syndrome (AS) and a deficiency in the Angelman syndrome (AS) and a deficiency of the paternal region resulting in the Prader-Willi of the paternal region resulting in the Prader-Willi syndrome (PWS). syndrome (PWS).

Genomic imprintingGenomic imprinting

Prader WilliPrader Willi short stature short stature small hands and feet small hands and feet hypotonia and poor muscle hypotonia and poor muscle

development development excess fat, especially in excess fat, especially in

the central portion of the the central portion of the body body

narrow forehead narrow forehead almond shaped eyes with almond shaped eyes with

thin, down-turned lips thin, down-turned lips light skin and hair relative light skin and hair relative

to other family members to other family members lack of complete sexual lack of complete sexual

development in development in adolescence adolescence

Angelman SyndromeAngelman Syndrome

Angelman SyndromeAngelman Syndrome Severe developmental delay (100%) Severe developmental delay (100%) Minimal use of words or nonverbal; receptive skills higher than expressive Minimal use of words or nonverbal; receptive skills higher than expressive

skills (100%) skills (100%) Movement or balance disorder including, wide based gait with feet turned Movement or balance disorder including, wide based gait with feet turned

outward, tremulous movement of limbs, and uncoordinated movements outward, tremulous movement of limbs, and uncoordinated movements (100%) (100%)

Behavioral uniqueness such as frequent laughter or smiling, happy demeanor, Behavioral uniqueness such as frequent laughter or smiling, happy demeanor, easily excitable often with hand flapping movements, hypermotoric behavior easily excitable often with hand flapping movements, hypermotoric behavior (can be seen in infants as ceaseless activity), and a short attention span (can be seen in infants as ceaseless activity), and a short attention span (100%) (100%)

Microcephaly by age 2 (>80%) Microcephaly by age 2 (>80%) Seizures of any type by age 3 years (>80%) Seizures of any type by age 3 years (>80%) Abnormal EEG (>80%) Abnormal EEG (>80%) Strabismus (20-80%) Strabismus (20-80%) Tongue thrusting and suck and swallow disorders (20-80%) Tongue thrusting and suck and swallow disorders (20-80%) Feeding problems in infancy (20-80%) Feeding problems in infancy (20-80%) Hypopigmented skin and eyes (20-80%) Hypopigmented skin and eyes (20-80%) Hyperactive tendon reflexes (20-80%) Hyperactive tendon reflexes (20-80%) Uplifted arms when walking (20-80%) Uplifted arms when walking (20-80%) Prominent mandible (20-80%) Prominent mandible (20-80%) Wide mouth/wide spaced teeth (20-80%) Wide mouth/wide spaced teeth (20-80%)