Rachel Ma

IM I / 1 / 11 AP
1/20/17
Compiled Annotations

Acuna, R., Padilla, B. E., Florez-Ramos, C. P., Rubio, J. D., Herrera, J. C., Benavides, P.,
Rose, J. K. C. (2012). Adaptive horizontal transfer of a bacterial gene to an invasive
insect pest of coffee. Proceedings of the National Academy of Sciences, 109(11), 4197
4202. https://doi.org/10.1073/pnas.1121190109

This study examines the evidence of LGT from bacteria into the coffee berry borer beetle.
LGT has been associated with adaption to new environments, which is a possibility in this insect.
The beetle is a pest and a major threat to coffee production, exclusively feeding and reproducing
inside coffee seeds. Scientists proposed a specific protein allowing the beetle to digest coffee
bean, and the results show that a mannanase gene likely to have originated in gut bacteria
suggest potential gene transfer to the beetle. This study further suggests that intestinal bacteria
provides genetic material that allows adaption to new ecological niches and a necessity to
survive. Intestinal bacteria may a rich source of genes essential to organisms survival.
This article is vague in describing the impact of the study besides the fact that eukaryotes
can take genetic material from bacteria, and could include further implications in a broader
context.

Ahmed, M. Z., Breinholt, J. W., & Kawahara, A. Y. (2016). Evidence for common horizontal
transmission of Wolbachia among butterflies and moths. BMC Evolutionary Biology,
16(1). https://doi.org/10.1186/s12862-016-0660-x

Wolbachia bacteria strains are commonly found in arthropods, and the current study
found widely spread lateral transfer among butterfly and moth species. Wolbachia is an
intracellular bacteria that are transferred vertically from mother to offspring and live in symbiosis
with its hosts. It is a genus of facultative endosymbiont, meaning it can increase or decrease host
fitness through symbiosis, and commonly interacts with its host through parasitic manipulation
of the reproductive system. After it gains stability in the host genome, possible LGT will occur.
The study found that some possible causes of LGT are shared food sources and shared natural
enemies. However, results are not conclusive as to the effects of the transfers on the moths.
This article clearly describes the relationship between Wolbachia and its host species.
However, the results are not conclusive and require further experimentation to determine the
exact phenotypic changes induced by the Wolbachia gene transfers.

Alsmark, C., Foster, P. G., Sicheritz-Ponten, T., Nakjang, S., Martin Embley, T., & Hirt, R. P.
(2013). Patterns of prokaryotic lateral gene transfers affecting parasitic microbial
eukaryotes. Genome Biology, 14(2), R19. http://doi.org/10.1186/gb-2013-14-2-r19

Although many lateral gene transfers do not provide lasting changes within a genome,
some do create new functions that may help an organism survive. For example, a transfer to
microsporidian parasites gave them the ability to steal ATP from their host cells. This study
aimed to analyze the LGTs affecting the genomes of 13 microbial eukaryotes, providing insight
into the importance of LGT and the implications for understanding how metabolic pathways
have evolved. Most LGTs were found to be involved in metabolism-related functions. LGTs
were found for enzymes within mucosal parasites that mediate carbohydrate, glycan, amino acid,
and lipid metabolism. These enzymes happen to be the most crucial due to the need to process
these substrates for the parasites. Thus, some LGTs may have adaptive significance to the
species surroundings.
This article contains extensive data on the studys findings on LGT and provides some
examples of the impact LGT may have.

Bjerkvig, R., Tysnes, B. B., Aboody, K. S., Najbauer, J., & Terzis, A. J. A. (2005). The origin of
the cancer stem cell: current controversies and new insights. Nature Reviews Cancer,
5(11), 899904. http://doi.org/10.1038/nrc1740

This article analyzes the possible origins of the cancer stem cell - cells that have acquired
genetic mutations causing them to potentially orchestrate tumor initiation. Cancer stem cells
have been thoroughly discussed as to their origin and creation, some of the explanations being
aneuploidy, the microenvironment, and cell fusion; lateral gene transfer (LGT) is not excepted.
LGT may occur as a result of transformation (uptake from the environment), transduction
(introduction by a phage/virus) or conjugation (physical contact between donor and recipient
cells). Another method discussed in this article involves the phagocytosis of apoptotic cells. The
Epstein-Barr virus had previously integrated into cells and resulted in the uptake and transfer of
DNA into the cells nuclei. EBV-encoded genes were expressed at the protein level, indicating a
successful integration of the acquired genetic material. Chromosomes may have been
incorporated into cancer stem cells in such a way, initiating tumors through mutation.
Additionally, tumor cells may transfer genetic material to normal cells, furthering progression.
This article summarized the connections between LGT and cancer stem cells thoroughly
and provided resources for further study.

Brevini, T. A. L., Pennarossa, G., Manzoni, E. F. M., Gandolfi, C. E., Zenobi, A., & Gandolfi, F.
(2016). The quest for an effective and safe personalized cell therapy using epigenetic
tools. Clinical Epigenetics, 8, 119. https://doi.org/10.1186/s13148-016-0283-5

This article summarizes the current research towards cell therapy using epigenetic
methods. Understanding gene expression and how epigenetic modifications can alter them is the
key to the current clinical research. The current article details the usage of a small-molecule
method to interact and change the cells DNA expression. Methylation of histones on the gene
are a factor in how the gene will be processed and therefore drugs made to initiate methylation
could turn off certain cell expression factors. For example, HDAC inhibitors are able to induce a
cell cycle arrest at G1 or G2-M stage, cancer cell differentiation and apoptosis, all of which
contribute in inhibiting the rapid mutation and growth of cells. This increased cell plasticity
creates a variety of options for the cell to differentiate into another type. Epigenetic methods are
a versatile new front for research in cell therapy today.
Brown, J. R. (2003). Ancient horizontal gene transfer. Nature Reviews Genetics, 4(2), 121+.

This article examines the lateral (horizontal) gene transfer (LGT) hypothesized to have
played a major role in ancient evolution. In contrast to vertical inheritance seen mainly in
modern evolution, lateral transfer can occur between different organisms and species. The
emergence of the three domains of life, Archaea, Bacteria, and Eukarya, included much more
frequent LGT possibly because of early cells highly error-prone replication and vertical
inheritance. Early bacterial and archaeal species seem to share many genes, and some bacterial
pathogens have also acquired a smaller, but still significant, number of genes from their
eukaryotic plant and animal hosts.
This article places LGT into evolutionary context and reveals the background behind the
LGT seen today.

Danchin, E. G. J. (2016). Lateral gene transfer in eukaryotes: tip of the iceberg or of the ice
cube? BMC Biology, 14, 101. https://doi.org/10.1186/s12915-016-0330-x

This article discusses recent research on LGT in eukaryotes. LGTs prevalence has
challenged many of the preconceptions of evolution that scientists have formed. For example, an
E. coli cells genome could reach a variability of 80%. LGT plays roles in acquiring antibiotic
resistance and adapting to the environment. The reason why eukaryotic LGT is far less prevalent
than prokaryotic LGT lies in the separated germline of eukaryotes. The genes transferred thus
can not be integrated into the genome and the germline functions as a stringent barrier against
LGT. Studies done on eukaryotic species with LGT have concluded with lack of evidence for
LGT of prokaryotic origin cemented in eukaryotic genomes, and thus this phenomenon is neither
continuous nor prevalent. However, many other factors must be taken into consideration, and
although LGT in eukaryotes is not a generally occurring event, bacterial DNA in eukaryotes
remains a topic of discussion in contributing to the biology of various species.

Dong, J. Y., & Woraratanadharm, J. (2005). Gene therapy vector design strategies for the
treatment of cancer. Future Oncology, 1(3), 361+. Retrieved from
http://libproxy.howardcc.edu/login?
url=http://go.galegroup.com.libproxy.howardcc.edu/ps/i.do?
p=AONE&sw=w&u=colu91149&v=2.1&it=r&id=GALE
%7CA224966204&asid=c10c6609fc8117b9db73bf449118331b

Gene therapy vectors, once introduced into a patients genome, can be used as cancer
treatment in itself or to facilitate conventional cancer treatment options such as radio- and
chemotherapy. A variety of gene therapy approaches include re-establishing cell control,
programming apoptosis to eliminate cancer cells, stimulation of immune responses
(immunotherapy), restriction of blood supply to the cells (antiangiogenesis), and oncolytic viral
vectors. The primary goal for gene therapy is to include agents that have a high therapeutic index
(high potency against malignant cells) but only limited toxicity to benign cells. Currently, many
methods using the approaches described are still under development and are being reviewed to
ensure efficacy.
 This article provides a comprehensive overview of the current methods for gene therapy,
and will help clarify the background to future research on gene therapy.

Ed Yong. (2015, July 14). This Beetle is Ruining Your Coffee With the Help of Bacteria.

This article explains the coffee berry borer beetle phenomena. The beetle is the only
animal that can feed solely on coffee beans due to the high caffeine content. Caffeine acts as a
poison and paralyzes normal insects, except the coffee berry beetle borer. A separate study
analyzed how the beetle seemed to withstand the caffeine content: there were no traces found in
the beetles feces - something in their gut had destroyed the poison. When fed with antibiotics,
caffeine was present in their feces, and their eggs and larvae died immediately. Thus, bacteria
was found to be an important part of beetles health. Sometime in their history, the beetles stole a
gene from bacteria, and transferred permanently into their genome, helping them survive.
This article clarifies the importance of LGT and microbiology in an organism, and
explains the implications of a research study thoroughly.

Hotopp, J. C. D., Clark, M. E., Oliveira, D. C. S. G., Foster, J. M., Fischer, P., Torres, M. C. M.,
Werren, J. H. (2007). Widespread Lateral Gene Transfer from Intracellular Bacteria to
Multicellular Eukaryotes. Science, 317(5845), 17531756.

Despite lateral gene transfer (LGT) seeming only to rarely occur between bacteria and
multicellular eukaryotes, the presence of endosymbionts within eukaryotes may facilitate
bacterial gene transfers to eukaryotic host genomes. Segments of novel DNA have been
discovered within eukaryotes, despite LGT being rare. Therefore, the study analyzed how
Wolbachia pipientis, an endosymbiont that infects arthropods, could provide a way for transfer of
bacterial genes to eukaryotes. The study concluded that in some cases, segments or nearly the
entire Wolbachia genome was transferred successfully to the genome of the organism analyzed.
Bacterial sequences are commonly excluded from whole eukaryote genome sequencing projects
on the basis that they represent contamination.
The LGT events occurring in the study still maintain potential to provide new gene
function and possible genome evolution. Further research on different bacterial transfers can be
conducted.

Hotopp, Julie D. (2016, September 26). [Skype].

In this interview, Dr. Dunning Hotopp explained some of the specifics behind LGT and
talked about the future of LGT. These gene transfers occur most commonly in bacteria, due to
their asexual life cycle. The only way bacteria can develop variation to survive is through LGT,
whereas animals have reproduction and therefore do not rely of LGT. These gene transfers
sometimes become permanent in an organisms genome through selective pressure, when the
gene helps the organism survive. However, many genes in current experiments have not had
enough time to discern if they have became permanent in an organisms genome. The
hypothesized LGTs in humans would not be beneficial; according to the current view, they may
play a role in causing cancer. The next step, after constructing genes in plasmids and sequencing
these genes, would be to construct these genes in animal or insect cell lines and determining
differences in transcription.
The interview helped clarify some topics that are not detailed in individual studies, such
as where the research is heading in the future.

Huddleston, J. R. (2014). Horizontal gene transfer in the human gastrointestinal tract: potential
spread of antibiotic resistance genes. Infection and Drug Resistance, 167.
http://doi.org/10.2147/IDR.S48820

Antibiotic resistant infections remain a leading cause of death worldwide, but antibiotic
development has not increased to meet the need for treatment. Lateral gene transfer of resistance
genes from other bacteria is one of the ways bacterial resistance to antibiotics is developed. The
human gastrointestinal tract is one of the places in which this occurs, having many favorable
factors for LGT such as antibiotic exposure, high cell density, and the innate ability for gene
transfer. Among the three mechanisms for LGT, conjugation is the most frequently observed.
Conjugation involves the transfer of DNA through cell-to-cell contact and transfer of plasmid
DNA through a pilus. Reports of LGT in the lower gastronomical tract are becoming more
frequent, and the capability of emergence of resistant pathogens from this location is greater than
expected.
This article highlights one of the implications of LGT, placing LGT into context as a very
possible cause of antibiotic resistance in bacteria and linking LGT to a real-world problem.

Ioannidis, P., Johnston, K. L., Riley, D. R., Kumar, N., White, J. R., Olarte, K. T., Dunning
Hotopp, J. C. (2013). Extensively duplicated and transcriptionally active recent lateral
gene transfer from a bacterial Wolbachia endosymbiont to its host filarial nematode
Brugia malayi. BMC Genomics, 14(1), 639. http://doi.org/10.1186/1471-2164-14-639

This study sought to measure the extent of LGT in Brugia malayi, which are nematode
worms in a mutualistic symbiosis with Wolbachia bacteria. Transfers of DNA to B. malayi are
called nuclear Wolbachia transfers (nuwts). Most of the nuwts found were degenerate, meaning
they had no pressure to maintain their functionality. However, a select few had the potential for
functionality. Some nuwts were full-length genes, while some transferred as fragments or
degenerated over time to become fragments. Most nuwts in B. malayi were found to contain
single nucleotide polymorphisms (SNPs), which suggests that nuwts have been accumulating
over recent time in B. malayi. They were also found to be spread out in a continuous distribution,
suggesting that the transfer of DNA to the genome occured over a long life span. LGT in
eukaryotes is considered a rare phenomenon, because the domain is separate from bacteria.
However,10% of the Wolbachia genome had been successfully transferred to its host and have a
high possibility of some functional genes. This article assesses the implications of LGT between
bacteria and eukaryotes and their biological relevance in relation to the human genome.
This article provides detailed background on the mechanisms of LGT, and provides future
implications of LGT in medicine and health.
Paul N. Edwards. (n.d.). How to Read a Book, v5.0. University of Michigan School of
Information.

This article outlines strategies to effectively read and comprehend nonfiction books,
articles, and documents. Rather than focusing on details, it is more important to gain an
understanding of the text as a whole. Reading actively with purpose, using techniques such as
asking questions about the text, helps retain information. The most important strategy is to read
the text three times: once for an overview, the second time for understanding the text, and the
third for note-taking and remembering the content. When taking notes, using ones own words to
summarize the arguments, evidence and conclusion helps with remembering the text.
This articles strategies are important for successfully learning the information needed
from higher level scholarly articles, and will serve as a guide through extensive reading and
research.

Ravenhall, M., kunca, N., Lassalle, F., & Dessimoz, C. (2015). Inferring Horizontal Gene
Transfer. PLOS Computational Biology, 11(5), e1004095.

LGT is the transmission of portions of genomic DNA between organisms beyond that of
vertical inheritance. While it can be used to investigate the evolutionary relatedness of lineages
and species, different fragments of genome are the result of different evolutionary histories,
making it difficult to isolate specific LGT events. Because LGT can introduce a variety of
different genotypes from distant lineages, it is a major source of phenotypic innovation. HGT
events may not necessarily result in phenotypic changes, so most analyses stem from viewing the
genome data of a species. The two main methods of analyzing genomic sequence data are the
parametric and phylogenetic methods. Parametric methods search for a segment of a genome that
differs from the average, such as guanine-cytosine content. If a fragment of a genome has
deviated from the genomic signature (a sequence specific to a particular species), then it is likely
that LGT occurred. Phylogenetic methods examine evolutionary histories of genes and identify
conflicts between them. However, a main problem is that these methods vary and can create false
positives.
This article gives a recent and comprehensive assessment of the methods in which LGT is
analyzed, which will help the research in understanding procedures and data collection.

Riley, D. R., Sieber, K. B., Robinson, K. M., White, J. R., Ganesan, A., Nourbakhsh, S., &
Dunning Hotopp, J. C. (2013). Bacteria-Human Somatic Cell Lateral Gene Transfer Is
Enriched in Cancer Samples. PLoS Computational Biology, 9(6), e1003107.
http://doi.org/10.1371/journal.pcbi.1003107

This study examines the bacteria-human somatic cell LGT in cancer samples. Integration
into the human genome has been found to be detected more frequently in tumors than normal
samples, RNA than DNA samples, and the mitochondrial genome over the nuclear genome.
Because bacterial cells exposed to human somatic cells vastly outnumber them 10:1 and provide
constant contact and interaction, it is possible that LGT between the bacterial and somatic cells
may be associated with diseases such as cancer. As observed, various tumor cells sampled from
human and animals have been found to contain a greater number of bacterial genome inserts.
Bacterial integrations do in fact occur in the human somatic genome, and may play a role in
carcinogenesis - a topic vastly important in the current scientific frontier.
This article streamlines the current research on human-bacteria gene transfers, and
provides insight into future research.

Robinson, K. M., Sieber, K. B., & Hotopp, J. C. D. (2013). A review of bacteria-animal lateral
gene transfer may inform our understanding of diseases like cancer. PLoS Genetics,
9(10).

This article discusses the hypothesis that non-inherited bacterial DNA LGT into human
somatic cells could create mutations leading to cancer or other autoimmune diseases. Because
LGT occurs frequently in somatic cells yet can only become vertically inherited across
generations if occurring in germ cells, it usually is not detected. However, as there are 10 times
more bacterial cells than human cells in the body, there is an abundance of opportunity for
human somatic cells to undergo LGT. The non-inherited transfers of DNA to the human somatic
cell may act as a mutagen, causing mutations that may spiral out of control. Bacterial transfers
may also disrupt tumor suppressor genes and protooncogenes.
This article explains the connection between LGT and autoimmune diseases or cancer,
linking the disruption of human DNA to incorporation of bacteria into a genome.

Smets, B. F., & Barkay, T. (2005). Horizontal gene transfer: perspectives at a crossroads of
scientific disciplines. Nature Reviews Microbiology, 3(9), 675+.

This article gives a brief overview of LGT, including the process behind it and the
implications it holds. The steps needed for LGT to occur include preparation for transfer, transfer
of the DNA/RNA, entry into the recipient organism, establishment into the organism, and
potentially stable inheritance in the recipient genome to be passed down evolutionarily. LGT can
be seen as both an asset and detriment to our health and the environment. Many species of
human pathogenic bacteria are resistant to a variety of antibiotics, and the ability to transfer
antibiotic-resistant genes promotes such resistance. However, LGT also holds potential to help
augment genes and spread them to microorganisms, as well as improve food production.
This article helps identify the specific mechanism and cause behind LGT as well as the
outcomes caused by this biological phenomenon, giving a detailed overview on the subject.

Wirth, T., & Yl-Herttuala, S. (2014). Gene Therapy Used in Cancer Treatment. Biomedicines,
2(2), 149162. https://doi.org/10.3390/biomedicines2020149

This review summarizes gene therapies used in cancer treatment. Currently over 60% of
ongoing clinical gene therapy trials are targeting cancer, due to the unsatisfactory performance of
conventional cancer therapies. According to the review, the common traits of cancer include
insensitivity to anti-growth signals, limitless ability to replicate, and reduced apoptosis. The
microenvironment of non-malignant cells surrounding the tumor is very important in the
progression of cancer, and gene therapy aims to deliver genetic material into cells and express it
in hopes of benign effects. Two methods of doing so are by biological vectors (viruses) and
synthetic carriers (liposomes or nanoparticles). Both methods aim to target a specific tissue with
high transduction efficiency and sustain stable gene expression. While both have their
drawbacks, both are current methods utilizing the genome in cancer prevention.
The review effectively summarizes two methods used today for gene therapy.

Yoon, Jihee (2016). The Imperative Need to Consider the Bioethics of CRISPR-Cas9
Technology. National High School Journal of Science. Retrieved from
http://nhsjs.com/2016/the-imperative-need-to-consider-the-bioethics-of-crispr-cas9-
technology/

CRISPR-Cas9 is a novel technology that allows for precise gene editing, and provides a
possible mechanism for remedying gene mutations. However, recently the permissions granted to
scientists have sparked debate on the ethics and limitations to using CRISPR technology.
CRISPR technology allows for precise editing of DNA, allowing scientists to cut and paste
genes at certain sites to completely change an organisms genome. In the future, scientists could
be able to add genetically determined traits to organisms. CRISPR is a cheap, efficient, and
easily accessible type of gene editing, and so this highlights the concerns of its increasing use
worldwide. Firstly, CRISPR has uncertain safety issues; for example, the off-target effect
(unintentionally modifying the wrong sequence of DNA) or risks from editing multiple
sequences. Results are permanent yet the process is highly inaccurate. Furthermore, consent
limitations on embryonic experimentation as well as the ethics behind eugenics lead researchers
to be wary of the distribution of the CRISPR technology.
In the future, the debate over nature vs. technological advancement will continue to be
prevalent within this topic. The article provides a thorough discussion of the modern topics
surrounding CRISPR use.