Thirteen years after the human genome was sequenced, two
research groups have independently mapped the extent to which cells in
various organs in the body turn many thousands of genes into proteins.
From
bacteria to humans, genes are made up of units of DNA, called base
pairs. The sequence of base pairs in genes tell a cell's molecular
machinery what proteins to produce. Ultimately, it is the proteins that
carry out a myriad processes essential for life.
Once
the over three billion base pairs that make up the human genome were
sequenced, analysis of that data indicated that there are about 20,000
protein-coding genes.
In a paper just published in Nature,
an international team of scientists led by Akhilesh Pandey of the Johns
Hopkins University in the U.S and Harsha Gowda at the Institute of
Bioinformatics in Bangalore has drawn up a draft map of proteins
produced from 17,294 genes.
There was evidence for
proteins coming from 18,097 human genes, reported Bernhard Kuster of
Technische Universitaet Muenchen in Germany and his colleagues in a
separate paper published in the same issue of the journal.
The
two papers marked a “major advance”, providing comprehensive data about
proteins expressed in different human tissues, commented R. Nagaraj of
the Centre for Cellular & Molecular Biology in Hyderabad, who was
not involved in either study.
Dr. Pandey and his
colleagues examined proteins produced by normal cells in 30 tissue
samples, adult and foetal as well as those found in blood. They found
'housekeeping proteins' from 2,350 genes that were produced in all
tissues. On the other hand, proteins from 1,537 genes turned up in only
one of the tissues. A number of proteins were expressed only during
foetal development.
“The driving impetus for our work
was to develop a reference of what is normal for human organs and
cells,” said Dr. Pandey in an email. This information could provide
clues to biologists seeking to elucidate the function of individual
proteins. In addition, knowledge about organ-specific proteins could be
used for detection of diseases arising in those organs.
“The
day may not be too far when people have their protein profiles mapped,
much like [personal] genome sequencing we have today. This could help us
diagnose more diseases and diagnose diseases better too,” said Dr.
Satish Chandra, Director of NIMHANS and a coauthor of the paper at a
press conference in Bangalore.
In their paper, the
researchers reported detecting proteins from 193 regions in the human
genome that generally would not be expected to produce any, including
genes considered dysfunctional. This suggested that “we do not yet have a
thorough understanding of how our own genome works,” remarked Dr.
Pandey.
Although proteins from about 84 per cent of
all human genes had been found, those from the remaining genes may have
eluded detection, remarked Dr. Gowda, a Wellcome Trust-DBT India
Alliance Fellow. This could have occurred if the proteins were expressed
in tissues or organs that had not been sampled. Alternatively, they
might be expressed at very low levels, requiring special techniques to
track down.
A large number of scientists at the
Institute of Bioinformatics, a non-profit research organisation founded
and headed by Dr. Pandey, contributed to the study. Researchers at the
Postgraduate Institute of Medical Education & Research in
Chandigarh, the Armed Forces Medical College in Pune and the National
Institute of Mental Health and Neuro Sciences in Bangalore also
participated.
In the other Nature paper, Dr. Kuster
and his colleagues catalogued the proteins found in various human
tissues, cell lines and body fluids. They found that approximately
10,000-12,000 proteins were ubiquitously expressed.
Hundreds
of genes described in the human genome “apparently do not code for
protein any more,” observed Dr. Kuster. One example was a family of
proteins, involving some 800 genes, that are important for sensing smell
and taste. But proteins could not be found from more than half of those
genes.
“Our interpretation of that is that perhaps
modern humans don't rely so much on their sense of smell and taste as we
used to a long time ago. Therefore, evolution essentially gets rid of
those surplus genes at some point,” he told this correspondent.
On
the other hand, there were parts of the genome that had not been
associated with protein-coding potential but for which proteins turned
up. “So this could be a new playing ground, if you like, where nature
tries out new proteins and we don't necessarily know what they do yet,”
he remarked.
(with inputs from Divya Gandhi, Bangalore)
