Saturday, 27 July 2013

Evolution On the Inside Track: How Viruses in Gut Bacteria Change Over Time

Evolution On the Inside Track: How
Viruses in Gut Bacteria Change
Over Time
July 26, 2013 — Humans are far more
than merely the sum total of all the
cells that form the organs and
tissues. The digestive tract is also
home to a vast colony of bacteria of
all varieties, as well as the myriad
viruses that prey upon them.
Because the types of bacteria carried
inside the body vary from person to
person, so does this viral population,
known as the virome.
By closely following and analyzing the
virome of one individual over two-
and-a-half years, researchers from
the Perelman School of Medicine at
the University of Pennsylvania, led by
professor of Microbiology Frederic D.
Bushman, Ph.D., have uncovered
some important new insights on how
a viral population can change and
evolve -- and why the virome of one
person can vary so greatly from that
of another. The evolution and variety
of the virome can affect susceptibility
and resistance to disease among
individuals, along with variable
effectiveness of drugs.
Their work was published in the
Proceedings of the National Academy
of Sciences .
Most of the virome consists of
bacteriophages, viruses that infect
bacteria rather than directly attacking
their human hosts. However, the
changes that bacteriophages wreak
upon bacteria can also ultimately
affect humans.
"Bacterial viruses are predators on
bacteria, so they mold their
populations," says Bushman.
"Bacterial viruses also transport
genes for toxins, virulence factors
that modify the phenotype of their
bacterial host." In this way, an
innocent, benign bacterium living
inside the body can be transformed
by an invading virus into a dangerous
threat.
At 16 time points over 884 days,
Bushman and his team collected
stool samples from a healthy male
subject and extracted viral particles
using several methods. They then
isolated and analyzed DNA contigs
(contiguous sequences) using ultra-
deep genome sequencing .
"We assembled raw sequence data to
yield complete and partial genomes
and analyzed how they changed over
two and a half years," Bushman
explains. The result was the longest,
most extensive picture of the
workings of the human virome yet
obtained.
The researchers found that while
approximately 80 percent of the viral
types identified remained mostly
unchanged over the course of the
study, certain viral species changed
so substantially over time that, as
Bushman notes, "You could say we
observed speciation events."
This was particularly true in the
Microviridae group, which are
bacteriophages with single-stranded
circular DNA genomes. Several
genetic mechanisms drove the
changes, including substitution of
base chemicals; diversity-generating
retroelements, in which reverse
transcriptase enzymes introduce
mutations into the genome; and
CRISPRs (Clustered Regularly
Interspaced Short Palindromic
Repeats), in which pieces of the DNA
sequences of bacteriophages are
incorporated as spacers in the
genomes of bacteria.
Such rapid evolution of the virome
was perhaps the most surprising
finding for the research team.
Bushman notes that "different people
have quite different bacteria in their
guts, so the viral predators on those
bacteria are also different. However,
another reason people are so
different from each other in terms of
their virome, emphasized in this
paper, is that some of the viruses,
once inside a person, are changing
really fast. So some of the viral
community diversifies and becomes
unique within each individual."
Since humans acquire the bacterial
population -- and its accompanying
virome -- after birth from food and
other environmental factors, it's
logical that the microbial population
living within each of us would differ
from person to person. But this
work, say the researchers,
demonstrates that another major
explanatory factor is the constant
evolution of the virome within the
body. That fact has important
implications for the ways in which
susceptibility and resistance to
disease can differ among individuals,
as well as the effectiveness of
various drugs and other treatments.
The research was supported by
Human Microbiome Roadmap
Demonstration Project
(UH2DK083981) the Penn Genome
Frontiers Institute, and the University
of Pennsylvania Center for AIDS
Research (CFAR; P30 Al 045008).
Samuel Minot, Alexandra Bryson,
Christel Chehoud, Gary D. Wu, James
D. Lewis, all from Penn, are co-
authors.

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