SRY
Testes Determing
Factor
The Amino Acid Sequence
1
11 21
31 41
51
1 MQSYASAMLS
VFNSDDYSPA VQENIPALRR SSSFLCTESC NSKYQCETGE NSKGNVQDRV
60
61 KRPMNAFIVW SRDQRRKMAL ENPRMRNSEI SKQLGYQWKM
LTEAEKWPFF QEAQKLQAMH 120
121 REKYPNYKYR PRRKAKMLPK NCSLLPADPA SVLCSEVQLD
NRLYRDDCTK ATHSRMEHQL 180
181 GHLPPINAAS
SPQQRDRYSH WTKL
*The letters in red are the amino acids found in the HMG box. (60-128)
The SRY Protein
In Action
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There are several types of mutations that can result from mutations at the SRY gene and result in many different phenotypic variants. Variants are caused by mutations, or changes in the genetic code that lead to the coding of different amino acids. A one-letter change in the base pair sequence leads to a chain of events that first codes for an irregular amino acid, changes the shape of a normal SRY protein, and ultimately has an effect in the development of an individual. A table with the number of currenlty discovered genetic variants in the SRY protein are displayed here:
In the variants above, each
of the numbers displayed indicates the exact location of a variant base
pair. As true with any protein coding process, a single substitution
in any single base pair sequence for the SRY protein can have profound
consequences in the development of an individual. In the SRY protein,
a single variant occuring at the 60th
bp causes an amino acid change from the normal amino acid Valine (V) to
the amnio acid Anlanine (A). Phenyotypically, this change in amino
acids leads to developmental defects on the individual. In research,
this variant occurence was found in a three-generation family
where all XY individuals have this particular single base-pair substitution.
The variant resulted in three individuals that were XY sex-reversed females,
and two were XY males (Vilain E...).
The most common type of mutation
that occurs from genetic variation in the SRY region is Gonadal dysgenesis,
or Swyer Syndrome. Individuals with Gonadal dysgenesis suffer from
rapid and early degeneration of their gonads. Adults have what are
known as “streak gonads” that consist prominently of fibrous tissue and
variable amounts of ovarian stroma (OMIM). This condition in particular
has many variants on the way it is expressed in affected individuals.
Most individuals exhibit various types of sexual development, but never
develop secondary sexual characteristics when puberty is reached.
The genotypes are typically 46,XY females who either have partial or complete
Gonadal dysgenesis.
The SRY protein is somewhat of a special protein - it
has only one exon. Evidence for this finding has been studied
and published in Genomics "Evidence that the SRY protein is encoded by
a single exon on the human Y chromosome." (Genomics 736-739).
Its coding sequence codes for 204 amino acids from
a mRNA sequence that is 897 base pairs long- distributed in the following
among the four nucleotides:
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Since being mapped in 1989,
the SRY gene has been the focus of many research projects. Some of
the work that has become the most well-known confirms the function of the
SRY protien as a memeber of the HMG-box family proteins. For example,
a mutational analysis of the SRY gene in studied XY females noted that
all 11 of the mutations described at that time were within the DNA-binding
HMG-box region of the protein (Hawkins). In 1996, it was proposed
that only the HMG box region of the SRY gene has been conserved through
evolution, suggested that SRY function depends on the HMG box and therefore
acts as an architectural transcription factor (Kawakura). Since then,
there have been numerous studies of individuals with Gonadal dysgenesis,
and have added to the evidence of the mechanism in which the SRY functions.
Works Cited
1) Hawkins, J. R. :
2) Kawakura, K.; Miyake, Y.-I.; Murakami, R.-K.; Kondoh, S.; Hirata, T.-I.; Kaneda, Y. :
3) Vilain E, McElreavey K, Jaubert F, Raymond
JP, Richaud F, Fellous M
Familial case with sequence
variant in the testis-determining region associated with two sex phenotypes.
PubMed ID: 1570829
4) NCBI. Sex Determining Region Y.
Protein Link: