An Insight into the Use of Genome, Methylome and Gethylome in Synthetic Biology
Mohammed A. Ibrahim
The development of new molecular approaches in biology and biotechnology introduced new scientific terms which include genome, genomics, methylome and methylomics. These are currently used in the literature of molecular and synthetic biology to refer various molecular concepts and applications. The present study is about the requirement of new ome and omics terms. This is because there are unique structural and functional aspects associated with genome and methylome at specific regions in the DNA sequence which are not explained by the two currently used terms methylome and genome. There is a requirement for new ome/omics terms to refer specific structural and functional matters associated with particular specialized zones in the DNA sequences. These genomic regions contain both the fifth base methyl cytosine and the other four coding bases. Methylated and non methylated DNA sequences are involved in gene expression of RNA and proteins, beside their role in the structural organization of the DNA sequence and the chromosome. In this study I suggest introducing two words which are derived from the established scientific terms genome, genomics, methylome and methylomics. The two new derived words are: gethylome and gethylomics. I suggest that these two words might be useful and could be used to explain various issues related to specific regions in the DNA sequence and chromosomes of eukaryotic organisms which contain the fifth base. Furthermore, gethylomics will help to refer more precisely to new applications in synthetic biology and genomics to design or redesign specific gethylomic circuits.
Received: August 05, 2011;
Accepted: December 05, 2011;
Published: January 16, 2012
During last two decades, active research works in molecular biology have introduced
great achievements in the new basic and applied knowledge of molecular biotechnology
in a rationally motivated process for understanding of various structural and
functional aspects of genetic materials. As a result, molecular biologists have
faced the challenge to find new proper words to define new concepts in the field
of molecular biotechnology which have been continually introduced. These words
are required for proper explanation of the newly gained knowledge, models, conceptions
and views associated with the scientific efforts to investigate and understand
the mechanisms of various genetic phenomena at the molecular level. Consequently
new scientific terms have been introduced to define concepts related to new
discoveries at the molecular level in biology and biotechnology. Molecular biologists
and other scientists in particular those interested in bioinformatics started
to use widely two morphemes. These are -ome and -omic,
each is added as suffix at the end of many scientific terms to form the derivatives.
|| Main four scientific terms with suffix (-ome or -omic) used
in molecular genetics
Scientists working in the field of molecular biology and bioinformatics use
(-ome) suffix to refer to a totality of some sort. This comes from the Oxford
English Dictionary which distinguishes three different fields of application
for the (-ome) suffix. The one which is used in the field of molecular biology
is forming nouns with the sense "all constituents considered collectively" (Lederberg
and McCray, 2001). Reviewing the literature in the field of molecular biology
and bioinformatics showed there is long list of scientific terms with (-ome)
suffix. On the other hand, Omics.org defined omics as a general
term for a broad discipline of science and engineering for analyzing the interactions
of biological information objects in various omes. Furthermore, Omics.org
indicated that the main focus of omics is on 1) mapping information objects
such as genes, proteins and ligands, 2) finding interaction relationships among
the objects, 3) engineering the networks and objects to understand and manipulate
the regulatory mechanisms and 4) integrating various omes and omics subfields.
A more scholastic definition of omics was reported by Vallero
(2010), who defined omics as a shorthand term for computational, biological
subfields for describing very large-scale data collection and analysis, all
with the suffix -omics.
The data in Table 1 show the main terms with suffix -ome
or -omics currently used in the literature of molecular genetics and biotechnology.
GENOME AND GENOMICS
It is believed that the term genome was first presented in 1920
and it was attributed to Hans Winkler, who proposed the expression genom
for the haploid chromosome set (Lederberg and McCray, 2001).
On the other hand, the term genomics was introduced in September
1987 by McKusick and Ruddle (1987a, b)
as a name for their newly established journal. Various definitions have been
reported for genome and genomics; Genome org defined the genome as the
totality of the genetic material; whereas the term genomics
is defined by the same source as the omics approach research of genome
in biology. Another definition was reported by Nill
(2000) stated the following: The scientific study of genes and their role
in an organisms structure, growth, health, disease, resistance to disease
and their contribution to the shape, function and the development of those whole
organisms. Recently, Vallero (2010) defined the genome
as an entire genetic complement, i.e., all of the hereditary material
possessed by an organism. The same author gave two definitions for genomics:
1) study of genes, including their functions 2) study of the molecular organization
of genomes, their information content and the gene products they encode.
In this context it is worth mentioning that Lederberg and
McCray (2001) indicated in their article on the ome and omics
that the word genomics has the same narrower connotation today,
of emphasis on linear gene mapping and DNA sequencing. At the end of this
section I would like to sum up all above mentioned definitions of genome and
genomics and say that authors do agree on the general concept which is concerned
and emphasized on the basic linear molecule of DNA. Thus it is possible to state
that genome and genomics are scientific terms which refer to the structure and
function of DNA sequence which is composed of four nucleotides: adenine, cytosine,
guanine and thymine.
|| The main functions of DNA methylation
METHYLOME AND METHYLOMICS
Recent molecular studies have indicated that methylation of genomic DNA is
widely prevailed in most eukaryotic species and it is an ancient property of
these organisms which is characterized by conservative phylogenetic features
and it is one of important epigenetic mechanisms which control gene expression
(Ibrahim et al., 2009; Feng
et al., 2010; Ibrahim, 2010a-c;
Jeltsch, 2010; Zemach et al.,
2010; Ibrahim, 2011). DNA methylation is a result
of addition of a methyl group at position 5 of the cytosine pyrimidine
ring next guanine in CpG dinucleotides. Consequently, DNA methylation might
disrupt the binding of transcription factors and draws methyl-binding proteins
which are linked with gene silencing and chromatin packaging (Weissbach,
1993; Strathdee and Brown 2002; Ibrahim,
2010a, b). Thus, methylated cytosine is considered
the fifth nitrogen base in the eukaryotic genome beside cytosine, guanine, thymine
and adenine (Adams, 1990; Lister
and Ecker, 2009). The wide-spread interest in investigation the DNA methylation
profile (methylome) of humans genome followed the great achievement in
sequencing of human genome. Currently research is ongoing to elucidate how the
genome executes the information it holds and the role of DNA methylation in
this process (McKusick and Ruddle, 1987a, b;
Beck and Rakyan, 2008; Lister and
Ecker, 2009; Bibikova et al., 2011). The
term methylome is now accepted in the scientific literature, it refers to the
totality of methylated DNA sites in a genome, cells and tissues (Methylome.Org).
On the other hand, the term methylomics refers to systematic
research that maps the histone codes and methylation patterns of healthy genomes
One of interesting points related to the concepts of methylome and methylomics
is that although all humans nucleated cells effectively contain the same
genome, they contain very different DNA methylation profiles (Guil
and Esteller, 2009). In addition, it has been reported that DNA methylation
is associated with changes in the cells phenotypes (Baron
et al., 2006), products of gene expression and in development of
various types of cancers (Ibrahim, 2010a, b;
Ogoshi et al., 2011), aging (Brunet
and Rando, 2007; Fraga and Esteller, 2007), fragile
X syndrome (Oostra and Willemsen, 2002), Beckwith-Weideman
syndrome (Maher and Reik, 2000) and pathogenesis of
psychiatric disorders (Mill et al., 2008; Ibrahim,
2010c). Investigation in this field indicated that DNA methylation might
be stable and reflect long term characteristics and persistent commitment along
a cell type and lineage (Baron et al., 2006).
The data presented in Table 2 summarize some of critical roles
which are played by DNA methylation.
GETHYLOME AND GETHYLOMICS
In the previous two sections I reviewed and discussed the concepts and definitions
of genome, genomics, methylome and methylomics. It is worth mentioning that
both genome and methylome share same structure, i.e., the duoble helix. However,
the only difference between two is the fifth nitrogen base, the methylated cytosine
(Adams, 1990; Lister and Ecker,
2009). And one more important point is that the DNA sequences which contain
methyl cytosine are few as compared with non methylated regions. The reported
results showed that approximately 1% of bases in a somatic human genome are
methyl-cytosines which equates to 70-80% of all CpG dinucleotides in the genome
(Ehrlich et al., 1982). In this respect, it is
important to distinguish between genome and methylome by noting that there are
differences in functional and structural aspects of both. The main function
of the genome is coding the information for protein and RNA production, whereas
methylome has completely different function which is associated with certain
aspects of control gene expression. Furthermore, methylated cytosines are the
sites on the DNA sequence for structural changes of genome. The changes at these
sites area result of occurrence of high rates of mutations as compared with
mutation rates which might occur in the normal dominant sites which are composed
of other four bases. These sites which contain methyl cytosine are known as
hot spots (Lutsenko and Bhagwat, 1999).
Another important point in this context is that hypomethylated DNA is associated
with active regions of the chromatin which enable gene expression, whereas hypermethylated
DNA is found in inactive chromatin (Razin and Cedar, 1977;
Razin, 1998). Taking into account these considerations
which are related to structure and function of methylome and genome, it might
be possible to understand the need for new ome and omics
to explain various basics and applications of the uniqueness of each form of
DNA and the interaction between both. Another point which is in support of this
argument is about the direct or indirect interactive states of methylome, genome
and histone(s) which might have very useful applications in synthetic biology.
Accordingly, it is worth considering the possibility of using new derived word
from genome and methylome to define and refer to specific molecular regions
which are composed of interactive structural and functional forms of methylome,
genome and histone(s). Hereby I suggest the word gethylome which
refers to specific interactive part(s) of genome and methylome with histone
and possibly other molecules. These molecular regions might form specific sets
and systems and are found in various regions of chromosomes. An example of gethylomic
regions are methylated CpG islands in the promoter regions and hot spots. Various
molecular tools (molecular biology, nano-biotechnology, bioinformatics and synthetic
biology tools) could be used to investigate the structural and functional properties
of gethylomic regions. Such studies might be conducted in the field of gethylomics.
Accordingly, I propose the following definition for gethylomics: Studying of
the molecular organization and functions of gethylomes and their contribution
and application in synthetic biology (Ibrahim, 2011).
SYNTHETIC BIOLOGY AND GETYLOMICS CIRCUITS
Synthetic biology is broadly defined as the re-design and fabrication
of existing biological systems (www.syntheticbiology.org),
this process includes engineering the networks and objects to understand and
manipulate the regulatory mechanisms. To perform this task there is a necessity
to build up genetic circuits and to uncover the design principles of natural
biological systems through the rational design of gene and protein circuits
(Mukherji and van Oudenaarden, 2009). Considering the
role of DNA methylation in gene expression, the interaction with histones and
the environment (Ibrahim, 2011; Zhang
et al., 2010), it is possible to imagine the importance of designing
and redesigning gethylomic genetic circuits. These circuits will have great
contribution and impact in improving the humans healths and might find
A recent published article showed that DNA biomolecules are suited substrates
for self-assembly and have proved to be a powerful scaffold with which it is
possible to design and build molecular devices with multiple forms and function
(Bhatia et al., 2011). In this respect, there
is another important point to add in this argument, that is the interaction
between the chromatin [chromatin is the complex of DNA and (histone) protein
of which the chromosomes are composed] and methylated regions of DNA sequence.
This interaction should be considered since active regions of the chromatin
which enable gene expression, are associated with hypomethylated DNA whereas
hypermethylated DNA is packaged in inactive chromatin (Razin
and Cedar, 1977; Razin, 1998). These chromosomal
regions might be good candidates for redesigning chromosomal circuits. Accordingly,
I expect that studies in the field of synthetic gethylomics will
have important applications in designing or redesigning of future gene molecular
Gethylomes are specific regions on the chromosomes which contain methyl cytosine and refer to specific interactive part(s) of genome and methylome with histone and possibly other molecules. These regions play important role in gene expression and structural changes of the genome. On the other hand, gethylomics focus on studies of the molecular organization and functions of gethylomes and their contribution and application in synthetic biology. The interactive components of glethyomic systems and their crucial role in gene expression will facilitate possible designing or redesigning of gethylomic circuits for future applications in synthetic biology.
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