Red and yellow parrot feathers

[RonO]

https://www.science.org/content/article/why-are-parrots-so-colorful-study-points-simple-chemical-tweak

There is a link to the research article in this news piece, but it may
not be open access. It is a pretty amazing molecular genetic analysis
coming out of an ecology and evolution group of researchers. They
utilized genomic sequence, long read RNA Seq, single cell RNA Seq, and
regulatory sequences involved in gene expression in feather cells.

They identified the causative gene for turning red feathers yellow, and
the possible causative mutation that is segregating in one species that
is responsible for the recessive red feather expression. The difference
in expression levels for the gene are not that great, but there is a
larger difference in single cell types. The enzyme is expressed in all
cells, but has higher expression in the yellow feathers. This increase
in expression is enough to convert enough red pigment to yellow to make
yellow feathers.

The only issue that I see in this paper is that they may not have the
causative mutation. They mapped the causative gene because there were 3
SNP (single nucleotide polymorphisms) found to be significant. They
mapped to possibly a small region of the genome flanking the ALDH3A2
gene, but two of the SNPs were on one contig and 1 SNP was on another
containing the gene. This means that there are issues with not having
continuous sequence in this region. It could be repetitive sequence or
issues with genome assembly. What they needed to do was long read
genomic sequencing of the region to obtain the continuous sequence in
order to determine if they were dealing with something like a retroviral
insertion or some other assembly issue. The causative mutation may
exist in the missing sequence between the two contigs.

In my own experience we have the recessive white allele at the C locus
in chickens. This mutation turns out to be due to a retroviral
insertion in an intron of the Tyrosinase gene that causes differential
splicing in epidermal cells, but normal splicing in other tissues. When
you assemble a genome out of short reads using a reference genome if the
reference genome (in our case it was Red Junglefowl that did not have
recessive white) you get two contigs cleanly separated from each other
with the retroviral insertion sequence missing. These researchers may
be having issues with something similar.

Ron Okimoto

Ron Okimoto

[John Harshman]

Post by RonO
https://www.science.org/content/article/why-are-parrots-so-colorful-study-points-simple-chemical-tweak
There is a link to the research article in this news piece, but it may
not be open access.  It is a pretty amazing molecular genetic analysis
coming out of an ecology and evolution group of researchers.  They
utilized genomic sequence, long read RNA Seq, single cell RNA Seq, and
regulatory sequences involved in gene expression in feather cells.
They identified the causative gene for turning red feathers yellow, and
the possible causative mutation that is segregating in one species that
is responsible for the recessive red feather expression.  The difference
in expression levels for the gene are not that great, but there is a
larger difference in single cell types.  The enzyme is expressed in all
cells, but has higher expression in the yellow feathers.  This increase
in expression is enough to convert enough red pigment to yellow to make
yellow feathers.
The only issue that I see in this paper is that they may not have the
causative mutation.  They mapped the causative gene because there were 3
SNP (single nucleotide polymorphisms) found to be significant.  They
mapped to possibly a small region of the genome flanking the ALDH3A2
gene, but two of the SNPs were on one contig and 1 SNP was on another
containing the gene.  This means that there are issues with not having
continuous sequence in this region.  It could be repetitive sequence or
issues with genome assembly.  What they needed to do was long read
genomic sequencing of the region to obtain the continuous sequence in
order to determine if they were dealing with something like a retroviral
insertion or some other assembly issue.  The causative mutation may
exist in the missing sequence between the two contigs.
In my own experience we have the recessive white allele at the C locus
in chickens.  This mutation turns out to be due to a retroviral
insertion in an intron of the Tyrosinase gene that causes differential
splicing in epidermal cells, but normal splicing in other tissues.  When
you assemble a genome out of short reads using a reference genome if the
reference genome (in our case it was Red Junglefowl that did not have
recessive white) you get two contigs cleanly separated from each other
with the retroviral insertion sequence missing.  These researchers may
be having issues with something similar.

Do you know what causes the defective splicing in epidermal cells?

[RonO]

Post by John Harshman

Post by RonO
https://www.science.org/content/article/why-are-parrots-so-colorful-
study-points-simple-chemical-tweak
There is a link to the research article in this news piece, but it may
not be open access.  It is a pretty amazing molecular genetic analysis
coming out of an ecology and evolution group of researchers.  They
utilized genomic sequence, long read RNA Seq, single cell RNA Seq, and
regulatory sequences involved in gene expression in feather cells.
They identified the causative gene for turning red feathers yellow,
and the possible causative mutation that is segregating in one species
that is responsible for the recessive red feather expression.  The
difference in expression levels for the gene are not that great, but
there is a larger difference in single cell types.  The enzyme is
expressed in all cells, but has higher expression in the yellow
feathers.  This increase in expression is enough to convert enough red
pigment to yellow to make yellow feathers.
The only issue that I see in this paper is that they may not have the
causative mutation.  They mapped the causative gene because there were
3 SNP (single nucleotide polymorphisms) found to be significant.  They
mapped to possibly a small region of the genome flanking the ALDH3A2
gene, but two of the SNPs were on one contig and 1 SNP was on another
containing the gene.  This means that there are issues with not having
continuous sequence in this region.  It could be repetitive sequence
or issues with genome assembly.  What they needed to do was long read
genomic sequencing of the region to obtain the continuous sequence in
order to determine if they were dealing with something like a
retroviral insertion or some other assembly issue.  The causative
mutation may exist in the missing sequence between the two contigs.
In my own experience we have the recessive white allele at the C locus
in chickens.  This mutation turns out to be due to a retroviral
insertion in an intron of the Tyrosinase gene that causes differential
splicing in epidermal cells, but normal splicing in other tissues.
When you assemble a genome out of short reads using a reference genome
if the reference genome (in our case it was Red Junglefowl that did
not have recessive white) you get two contigs cleanly separated from
each other with the retroviral insertion sequence missing.  These
researchers may be having issues with something similar.

Do you know what causes the defective splicing in epidermal cells?

They do not know the cause. For some reason the retroviral sequence
continues to be successfully spliced in certain tissues, but for some
cell types like epidermal cells there is a mess up and incorrect
splicing occurs so that a functional tyrosinase transcript is not
produced. It is the reason why the early protein work on recessive
white found functional tyrosinase expressed in recessive white birds.
That is the reason that recessive white was a black eyed white.
Tyrosinase was still produced in the retina, but it wasn't produced in
the feathers or leg scutes. Tyrosinase is produced in the dermis. That
is why the normal junglefowl dermal pigmentation of the shank can be
express in white feathered breeds like the French Bresse breed of
chickens and recessive white Silkie that has pigmented dermal and
internal tissue pigmentation. Silkies have black muscles, connective
tissue and bones.

The retroviral insertion affects splicing in a tissue specific manner.

https://www.ambresse.com/french-bresse-chicken.html#:~:text=Bresse%20growth%20rate%20outstrips%20the,higher%20prices%20in%20the%20marketplace.

Ron Okimoto

[John Harshman]

Post by John Harshman

Post by RonO
https://www.science.org/content/article/why-are-parrots-so-colorful-
study-points-simple-chemical-tweak
There is a link to the research article in this news piece, but it
may not be open access.  It is a pretty amazing molecular genetic
analysis coming out of an ecology and evolution group of
researchers.  They utilized genomic sequence, long read RNA Seq,
single cell RNA Seq, and regulatory sequences involved in gene
expression in feather cells.
They identified the causative gene for turning red feathers yellow,
and the possible causative mutation that is segregating in one
species that is responsible for the recessive red feather
expression.  The difference in expression levels for the gene are not
that great, but there is a larger difference in single cell types.
The enzyme is expressed in all cells, but has higher expression in
the yellow feathers.  This increase in expression is enough to
convert enough red pigment to yellow to make yellow feathers.
The only issue that I see in this paper is that they may not have the
causative mutation.  They mapped the causative gene because there
were 3 SNP (single nucleotide polymorphisms) found to be
significant.  They mapped to possibly a small region of the genome
flanking the ALDH3A2 gene, but two of the SNPs were on one contig and
1 SNP was on another containing the gene.  This means that there are
issues with not having continuous sequence in this region.  It could
be repetitive sequence or issues with genome assembly.  What they
needed to do was long read genomic sequencing of the region to obtain
the continuous sequence in order to determine if they were dealing
with something like a retroviral insertion or some other assembly
issue.  The causative mutation may exist in the missing sequence
between the two contigs.
In my own experience we have the recessive white allele at the C
locus in chickens.  This mutation turns out to be due to a retroviral
insertion in an intron of the Tyrosinase gene that causes
differential splicing in epidermal cells, but normal splicing in
other tissues. When you assemble a genome out of short reads using a
reference genome if the reference genome (in our case it was Red
Junglefowl that did not have recessive white) you get two contigs
cleanly separated from each other with the retroviral insertion
sequence missing.  These researchers may be having issues with
something similar.

Do you know what causes the defective splicing in epidermal cells?

They do not know the cause.  For some reason the retroviral sequence
continues to be successfully spliced in certain tissues, but for some
cell types like epidermal cells there is a mess up and incorrect
splicing occurs so that a functional tyrosinase transcript is not
produced.  It is the reason why the early protein work on recessive
white found functional tyrosinase expressed in recessive white birds.
That is the reason that recessive white was a black eyed white.
Tyrosinase was still produced in the retina, but it wasn't produced in
the feathers or leg scutes.  Tyrosinase is produced in the dermis.  That
is why the normal junglefowl dermal pigmentation of the shank can be
express in white feathered breeds like the French Bresse breed of
chickens and recessive white Silkie that has pigmented dermal and
internal tissue pigmentation.  Silkies have black muscles, connective
tissue and bones.
The retroviral insertion affects splicing in a tissue specific manner.
https://www.ambresse.com/french-bresse-chicken.html#:~:text=Bresse%20growth%20rate%20outstrips%20the,higher%20prices%20in%20the%20marketplace.
Ron Okimoto

Perhaps the mutation introduces a binding site for some transcription
factor or regulatory RNA that's expressed only in epidermal cells, and
this happens to interfere with splicing?

[RonO]

Post by John Harshman

Post by John Harshman

Post by RonO
https://www.science.org/content/article/why-are-parrots-so-colorful-
study-points-simple-chemical-tweak
There is a link to the research article in this news piece, but it
may not be open access.  It is a pretty amazing molecular genetic
analysis coming out of an ecology and evolution group of
researchers.  They utilized genomic sequence, long read RNA Seq,
single cell RNA Seq, and regulatory sequences involved in gene
expression in feather cells.
They identified the causative gene for turning red feathers yellow,
and the possible causative mutation that is segregating in one
species that is responsible for the recessive red feather
expression.  The difference in expression levels for the gene are
not that great, but there is a larger difference in single cell
types. The enzyme is expressed in all cells, but has higher
expression in the yellow feathers.  This increase in expression is
enough to convert enough red pigment to yellow to make yellow feathers.
The only issue that I see in this paper is that they may not have
the causative mutation.  They mapped the causative gene because
there were 3 SNP (single nucleotide polymorphisms) found to be
significant.  They mapped to possibly a small region of the genome
flanking the ALDH3A2 gene, but two of the SNPs were on one contig
and 1 SNP was on another containing the gene.  This means that there
are issues with not having continuous sequence in this region.  It
could be repetitive sequence or issues with genome assembly.  What
they needed to do was long read genomic sequencing of the region to
obtain the continuous sequence in order to determine if they were
dealing with something like a retroviral insertion or some other
assembly issue.  The causative mutation may exist in the missing
sequence between the two contigs.
In my own experience we have the recessive white allele at the C
locus in chickens.  This mutation turns out to be due to a
retroviral insertion in an intron of the Tyrosinase gene that causes
differential splicing in epidermal cells, but normal splicing in
other tissues. When you assemble a genome out of short reads using a
reference genome if the reference genome (in our case it was Red
Junglefowl that did not have recessive white) you get two contigs
cleanly separated from each other with the retroviral insertion
sequence missing.  These researchers may be having issues with
something similar.

Do you know what causes the defective splicing in epidermal cells?

They do not know the cause.  For some reason the retroviral sequence
continues to be successfully spliced in certain tissues, but for some
cell types like epidermal cells there is a mess up and incorrect
splicing occurs so that a functional tyrosinase transcript is not
produced.  It is the reason why the early protein work on recessive
white found functional tyrosinase expressed in recessive white birds.
That is the reason that recessive white was a black eyed white.
Tyrosinase was still produced in the retina, but it wasn't produced in
the feathers or leg scutes.  Tyrosinase is produced in the dermis.
That is why the normal junglefowl dermal pigmentation of the shank can
be express in white feathered breeds like the French Bresse breed of
chickens and recessive white Silkie that has pigmented dermal and
internal tissue pigmentation.  Silkies have black muscles, connective
tissue and bones.
The retroviral insertion affects splicing in a tissue specific manner.
https://www.ambresse.com/french-bresse-
chicken.html#:~:text=Bresse%20growth%20rate%20outstrips%20the,higher%20prices%20in%20the%20marketplace.
Ron Okimoto

Perhaps the mutation introduces a binding site for some transcription
factor or regulatory RNA that's expressed only in epidermal cells, and
this happens to interfere with splicing?

My take is that it will eventually be figured out because it is an
unusually regulated mutation. Something is interferring in epidermal
cells, and it should be some type of tissue specific regulation. The
crazy thing is that it might have something to do with temperature
sensitvity like a reverse of siamese cats tyrosinase (active enzyme is
only produced at below body temperature in affected cats). In this case
recessive white chicks can hatch with black down for some chicks, so the
correct splicing can occur when the skin is 37 degrees C, but not for
all cases. Most of the time the down lacks black pigment. The black
downed chicks feather out white. The same feather folicles that
produced black down before hatch produce white chick, juvenile and adult
feathers.

Ron Okimoto

[DB Cates]

Post by RonO

Post by John Harshman

Post by John Harshman

Post by RonO
https://www.science.org/content/article/why-are-parrots-so-
colorful- study-points-simple-chemical-tweak
There is a link to the research article in this news piece, but it
may not be open access.  It is a pretty amazing molecular genetic
analysis coming out of an ecology and evolution group of
researchers.  They utilized genomic sequence, long read RNA Seq,
single cell RNA Seq, and regulatory sequences involved in gene
expression in feather cells.
They identified the causative gene for turning red feathers yellow,
and the possible causative mutation that is segregating in one
species that is responsible for the recessive red feather
expression.  The difference in expression levels for the gene are
not that great, but there is a larger difference in single cell
types. The enzyme is expressed in all cells, but has higher
expression in the yellow feathers.  This increase in expression is
enough to convert enough red pigment to yellow to make yellow feathers.
The only issue that I see in this paper is that they may not have
the causative mutation.  They mapped the causative gene because
there were 3 SNP (single nucleotide polymorphisms) found to be
significant.  They mapped to possibly a small region of the genome
flanking the ALDH3A2 gene, but two of the SNPs were on one contig
and 1 SNP was on another containing the gene.  This means that
there are issues with not having continuous sequence in this
region.  It could be repetitive sequence or issues with genome
assembly.  What they needed to do was long read genomic sequencing
of the region to obtain the continuous sequence in order to
determine if they were dealing with something like a retroviral
insertion or some other assembly issue.  The causative mutation may
exist in the missing sequence between the two contigs.
In my own experience we have the recessive white allele at the C
locus in chickens.  This mutation turns out to be due to a
retroviral insertion in an intron of the Tyrosinase gene that
causes differential splicing in epidermal cells, but normal
splicing in other tissues. When you assemble a genome out of short
reads using a reference genome if the reference genome (in our case
it was Red Junglefowl that did not have recessive white) you get
two contigs cleanly separated from each other with the retroviral
insertion sequence missing.  These researchers may be having issues
with something similar.

Do you know what causes the defective splicing in epidermal cells?

They do not know the cause.  For some reason the retroviral sequence
continues to be successfully spliced in certain tissues, but for some
cell types like epidermal cells there is a mess up and incorrect
splicing occurs so that a functional tyrosinase transcript is not
produced.  It is the reason why the early protein work on recessive
white found functional tyrosinase expressed in recessive white birds.
That is the reason that recessive white was a black eyed white.
Tyrosinase was still produced in the retina, but it wasn't produced
in the feathers or leg scutes.  Tyrosinase is produced in the dermis.
That is why the normal junglefowl dermal pigmentation of the shank
can be express in white feathered breeds like the French Bresse breed
of chickens and recessive white Silkie that has pigmented dermal and
internal tissue pigmentation.  Silkies have black muscles, connective
tissue and bones.
The retroviral insertion affects splicing in a tissue specific manner.
https://www.ambresse.com/french-bresse-
chicken.html#:~:text=Bresse%20growth%20rate%20outstrips%20the,higher%20prices%20in%20the%20marketplace.
Ron Okimoto

Perhaps the mutation introduces a binding site for some transcription
factor or regulatory RNA that's expressed only in epidermal cells, and
this happens to interfere with splicing?

My take is that it will eventually be figured out because it is an
unusually regulated mutation.  Something is interferring in epidermal
cells, and it should be some type of tissue specific regulation.  The
crazy thing is that it might have something to do with temperature
sensitvity like a reverse of siamese cats tyrosinase (active enzyme is
only produced at below body temperature in affected cats).  In this case
recessive white chicks can hatch with black down for some chicks, so the
correct splicing can occur when the skin is 37 degrees C, but not for
all cases.  Most of the time the down lacks black pigment.  The black
downed chicks feather out white.  The same feather folicles that
produced black down before hatch produce white chick, juvenile and adult
feathers.
Ron Okimoto

Thanks for things like this. Something to pique the interest of a high
ignorance of the subject individual like me and a reminder that life is
a very weird and convoluted chemistry hack.