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A CURIOUS CASE OF GENETIC RESSURRECTION.
By Benjamin Lester

Some genes just won't stay dead. Between 40 million and 50 million
years ago, a slice of DNA called IRGM stopped functioning in the
ancestors of modern-day monkeys. But 25 million years later, in the
lineage that led to humans and great apes, three random events turned
the gene back on.

In mammals such as rats and dogs, IRGM (immunity-related GTPase
family, M) helps protect from bacterial pathogens such as salmonella.
Humans and apes also appear to use the gene. Our bodies produce a
functional version of the IRGM protein, and genetic studies have
identified deletions near the gene as a risk factor in Crohn's
disease, an autoimmune condition of the gastrointestinal tract. But
the precise role of IRGM in humans and apes remains unclear.

Interested in the gene's evolution, Evan Eichler, a human geneticist
at the University of Washington, Seattle, and his colleagues sequenced
IRGM in various species of primates. In monkeys, the team discovered a
piece of what could be "junk DNA" wedged in at the start of the gene.
This insertion mucks up the gene's promoter, a critical region for
protein production. To make matters worse, the monkey gene sports a
number of "stop codons," a type of genetic red light that prevents the
production of any functional protein. "We looked at about 15 species
of New and Old world monkeys," says Eichler. "[A]ll of those species
... have multiple stop codons, telling us that the gene is dead."

But humans, apes, and monkeys share a common ancestor, so IRGM must
have been resurrected somewhere along the line. As Eichler's group
reports today in PLoS Genetics, the most plausible
explanation--unlikely as it sounds--is that three random events
brought the gene back to life.

Based on genetic differences between monkeys, apes, and humans,
Eichler's group was able to create a picture of how the gene evolved
over the past 50 million years. First, the DNA remains of an ancient
virus, called an endogenous retrovirus, jumped from somewhere else in
the genome into the region directly upstream of the dormant IRGM gene,
creating a brand-new promoter. Then, two more mutations removed the
remaining stop signs. Together, these three unrelated events restored
the gene's function.

Eichler says that there's still much to learn about IRGM. "The
million-dollar question is: Does the new gene act the same way as the
old gene did? And we're not 100% sure." Perhaps the body is still
getting used to it, says Steven McCarroll, a geneticist at the
Massachusetts Institute of Technology in Cambridge. He notes that
different human populations show different IRGM activity patterns.
This may be because humans are still working out exactly how to use
this relatively new gene, he says: "This locus is revealing itself to
be 'under construction.'"

________________________________________________

1. Quem fez o teste com o gene inativo nos primatas?
R-

2. Quais foram os três eventos que trouxeram o gene IRGM de volta?
R-

Aí está. Boa Sorte à todas!

Marcadores: fics

Traduzam o texto abaixo e respondam às duas perguntas.
Os e-mails só serão aceitos até 13 de março (sexta-feira).

A CURIOUS CASE OF GENETIC RESSURRECTION.
By Benjamin Lester

Some genes just won't stay dead. Between 40 million and 50 million
years ago, a slice of DNA called IRGM stopped functioning in the
ancestors of modern-day monkeys. But 25 million years later, in the
lineage that led to humans and great apes, three random events turned
the gene back on.

In mammals such as rats and dogs, IRGM (immunity-related GTPase
family, M) helps protect from bacterial pathogens such as salmonella.
Humans and apes also appear to use the gene. Our bodies produce a
functional version of the IRGM protein, and genetic studies have
identified deletions near the gene as a risk factor in Crohn's
disease, an autoimmune condition of the gastrointestinal tract. But
the precise role of IRGM in humans and apes remains unclear.

Interested in the gene's evolution, Evan Eichler, a human geneticist
at the University of Washington, Seattle, and his colleagues sequenced
IRGM in various species of primates. In monkeys, the team discovered a
piece of what could be "junk DNA" wedged in at the start of the gene.
This insertion mucks up the gene's promoter, a critical region for
protein production. To make matters worse, the monkey gene sports a
number of "stop codons," a type of genetic red light that prevents the
production of any functional protein. "We looked at about 15 species
of New and Old world monkeys," says Eichler. "[A]ll of those species
... have multiple stop codons, telling us that the gene is dead."

But humans, apes, and monkeys share a common ancestor, so IRGM must
have been resurrected somewhere along the line. As Eichler's group
reports today in PLoS Genetics, the most plausible
explanation--unlikely as it sounds--is that three random events
brought the gene back to life.

Based on genetic differences between monkeys, apes, and humans,
Eichler's group was able to create a picture of how the gene evolved
over the past 50 million years. First, the DNA remains of an ancient
virus, called an endogenous retrovirus, jumped from somewhere else in
the genome into the region directly upstream of the dormant IRGM gene,
creating a brand-new promoter. Then, two more mutations removed the
remaining stop signs. Together, these three unrelated events restored
the gene's function.

Eichler says that there's still much to learn about IRGM. "The
million-dollar question is: Does the new gene act the same way as the
old gene did? And we're not 100% sure." Perhaps the body is still
getting used to it, says Steven McCarroll, a geneticist at the
Massachusetts Institute of Technology in Cambridge. He notes that
different human populations show different IRGM activity patterns.
This may be because humans are still working out exactly how to use
this relatively new gene, he says: "This locus is revealing itself to
be 'under construction.'"

________________________________________________

1. Quem fez o teste com o gene inativo nos primatas?
R-

2. Quais foram os três eventos que trouxeram o gene IRGM de volta?
R-

Aí está. Boa Sorte à todas!

Marcadores: fics

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