William Grover
Lateral Gene Transfer
Lateral Gene Transfer (LGT), also called Horizontal Gene Transfer (HGT), is the
movement of a piece of genetic material from one cell into another cell that is not the
progeny of the first cell. In other words, LGT is the movement of genes between
distantly related organisms (1). The word lateral is used to contrast the event with
vertical gene transfer, which is the passage of genetic material from a parent to its
progeny. For most of the history of genetics, vertical gene transfer was the only transfer
known, but since the 1980s, lateral gene transfer has become increasingly studied. In
1985, a researcher proposed that lateral gene transfers of functional genes between two
different species may not only be possible, but that it is “an important factor in evolution”
(2).
The transfer of DNA from one organism to another is one way in which an
organism can acquire new genes. In single cellular species, LGT enables the evolution of
antibiotic resistance, metabolic pathways, pathogenicity, and other important components
of the cell. The lateral transfer of functional genes has been shown many times through
experiments. For example, one study showed how genes involved in metabolism in
plankton were transferred to another species. The study observed planktonic bacteria,
archaea, and eukarya that reside and compete in the oceans’ photic zone, the top part of
the water where there is pervasive light. Certain bacteria in this environment contain
photoproteins called proteorhodopsins, which contribute to cellular metabolism. Before
this study, proteorhodopsin genes had only been well documented in a few kinds of
bacteria. However, these genes are also found in a certain order of archaea. The study
suggests that an LGT occurred between the species. Most of the archaea that contained
the proteorhodopsin gene had the gene in one specific place, adjacent to their smallsubunit ribosomal RNA. However, other archaea had proteorhodopsin genes in other
genomic regions. Although archaea of this family can be found throughout the water
column, the ones with proteorhodopsins were found only in the photic zone. The patchy
distribution of proteorhodopsin genes among archaea reflects their light-dependent fitness
contributions. That is, if this study is correct, functional genes can be transferred and
those genes can affect evolution (3).
But how did the study determine that the gene was acquired by lateral transfer?
Traditionally, scientists detect the presence of genes that have been laterally transferred
by looking for DNA that seems atypical, often in regards to GC content, when compared
to the majority of the DNA in a given genome. Genes whose features are “sufficiently
atypical—lying beyond a threshold value” are considered foreign. While this approach
can be useful, it has some inherent drawbacks. For instance, if a gene from a similar
species is transferred, it could easily avoid detection (4). However, this is still a good
way to identify possible LGTs and, luckily, the potentially transferred gene can be more
conclusively tested. In the above experiment with the archaea, “genomic context and
phylogenetic relationships” of the archaeal and bacterial proteorhodopsins were studied.
In other words, the researchers looked at the location of genes within the genome and the
distribution of similar genes across species. If a gene is in several different places within
a family, LGT is considered more possible.
Even better evidence is a jump in
phylogeny, the evolutionary development of
genomes. If a gene that has no predecessors
appears in a genome, LGT becomes very
likely. Gene-trees, such as the one shown to
the right, are constructed to visualize this
process. Each tree leaf, HF70_15C09 for
example, is a proteorhodopsin or
proteorhodopsin-like gene is a different
species. The GC content refers to the
nucleotide composition of the
proteorhodopsin genes. The genes used in
the study are in bold. The colors indicate
what kind of organism the gene is found in: blue, archaea; magenta, bacteria; black,
uncertain. The distances between the genes on the chart are relative distances based on
differences in sequences between genes. While this technique is not perfect, it can
provide a good indication that LGT has occurred (3).
When most people study LGT, they focus on either the phylogenies (the
evolutionary development) of specific genes that may have been transferred, or on
estimating the amount of an individual genome that is derived from LGT. These kinds of
tests recognize that LGT is important to prokaryotic evolution, but one group of scientists
believes that LGT may be much more important than most think. They say LGT has the
ability to cause “massive and complex transformations in basic biology.” This may be
manifested in the patchy distribution of a seemingly fundamental property (such as
aerobiosis) among the members of a group that are defined by other properties they have
in common, like morphological or molecular similarity. For example, LGT may enable
one kind of bacteria to live in an oxygen-rich environment though it is in every other way
similar to the members of a family of bacteria that cannot. The lineage of the recipients
of this gene may be included in a different group of taxonomy, or may even be
considered to comprise a new group.
There is some division on the issue of how to usefully define and recognize the
taxonomic classification of prokaryotes because it is difficult to determine phylogenetic
lineages. Before we knew about lateral gene transfer, prokaryotes were identified
according to key physiological adaptations, that is, if they were photosynthetic, could fix
nitrogen, could metabolize sulfur, etc. These traits are seemingly fundamental, so such
properties would seem to be excellent guidelines to make a comprehensive gene-tree to
relate contemporary groups. Unfortunately, only small taxonomic trees make sense
because these seemingly fundamental properties are often distributed in unexplainable
ways (before the discovery of LGT). Therefore, LGT can significantly change the way
we look at the evolution and relations of prokaryotes (5).
Since the 1980s, the amount of lateral gene transfer that has occurred in microbial
evolution has been “heavily debated” (5). Some scientists say that LGT is not an
important process in evolution at all, while others believe it is essential to understanding
prokaryotic evolution. Based on gene-tree analysis, scientists’ opinions range from the
belief that the genes of an average prokaryotic genome are 2% to 60% affected by LGT.
This 30-fold difference is an indication of the uncertainty this kind of comparison
produces and is the cause for the heavy debate. In an attempt to clarify this issue, a group
of scientists inferred the size of ancestral prokaryotic genomes that would result if
modern genomes came about without LGT. These inferred ancestral genome sizes were
invariably huge and so were reduced to a logical size by the inclusion of LGT. So rather
than looking at phylogenetic congruence, or comparing the way evolutionary
development occurred in different species (gene-tree analysis), the scientists considered
how much LGT it would take to keep in line with the assumption that genome sizes have
not significantly changed for prokaryotes. The method gives a “very conservative lowerbound” estimate that two-thirds of all gene-families have been affected by LGT. They
went on to claim that, all prokaryotic gene families have most likely been affected.
Though providing only a lower bound does not spell out the effect of LGT completely,
this study does lend credence to the claim that LGT is a very important process for
prokaryotic evolution (6).
Although lateral gene transfer seems to occur frequently from one bacterium to
another, most scientists do not believe there is a high occurrence of LGT from bacteria to
multicellular eukaryotes. However, one recent study provides evidence for the claim that
endosymbiotic bacteria, bacteria that live within a host cell and share a symbiotic
relationship with that cell, may participate in such a transfer fairly often. The study
concentrated on an endosymbiont called Wolbachia pipientis, which can be found in the
germ lines of some nematodes and insects. The researchers examined host genomes for
evidence of gene transfer events from Wolbachia bacteria to their hosts. From a group of
cells they knew to contain Wolbachia, they identified which cells had had genes
transferred into them by cleansing the cells of Wolbachia and checking to see if
Wolbachia genes were still present. To do this, they used Fluorescence In Situ
Hybridization (FISH), which involves the binding of fluorescent probes to specific genes
(two Wolbachia genes in this case). As can be seen in the picture below, this method
showed the presence of these incorporated Wolbachia genes.
They were able to confirm 4 insect and 4 nematode species with transfers that
range from short pieces (less than 500 base pairs) to nearly the entire Wolbachia genome
(more than a megabase). They found that nearly the entire Wolbachia genome was
transferred to a fly genome by the presence of PCR amplified products from 44 of 45
physically distant Wolbachia genes from a fly chromosome. The chromosome had been
treated with antibiotics and checked for the presence of Wolbachia with microscopy. In
contrast, a control line lacking the inserts and treated in the same way did not yield any
Wolbachia gene products from PCR. Since the 45 genes were spaced throughout the
Wolbachia genome, they concluded that nearly the entire Wolbachia genome had been
laterally transferred to the fly.
The scientists were also able to show that some of the inserted genes were
passed down to the hosts’ progeny, even when there was no Wolbachia to be found in the
progeny. Crosses between Wolbachia-free male fruit flies (with an insert of Wolbachia
genes) and Wolbachia-free females (without the insert) resulted in all of the offspring
having the insert. So the scientists concluded that the laterally transferred gene could be
inherited. Wolbachia infections are maternally inherited and the mothers could not have
passed a Wolbachia infection down to their progeny because they were not infected.
From all this, the researches concluded that even a multicellular eukaryote can acquire
new genetic material from LGT (1).
Though lateral gene transfer from bacteria to multicellular eukaryotes is possible,
the importance of LGT to higher eukaryotes is still debatable. When the International
Human Genome Sequencing Consortium published its draft of the human genome in
2001, several hundred genes were noted as being possible transfers from bacterial
genomes. The scientists who worked on the sequencing project found highly significant
similarities between these human genes and bacterial genes in BLAST searches and these
same genes lacked matches among non-vertebrate eukaryote genes. If all these genes
really were the result of lateral transfer from bacteria, it would mean that a significant
portion of the human genome was the direct result of LGT. However, many of these
genes were later rejected as possible LGTs by several methods including discovery of
probably orthologs from the genomes of eukaryotes that were subsequently sequenced
(7). Even if lateral gene transfer turns out not to be a direct contributor to the human
genome, LGT will continue to be a popular subject of study, and we will continue to
learn more about this important genetic process.
Works Cited
(1) Hotopp, Julie C. Dunning et al. “Widespread Lateral Gene Transfer from Intracellular
Bacteria to Multicellular Eukaryotes.” Science 21 September 2007 317: 1753-1756.
(2) Syvanen, Michael. “Cross-species Gene Transfer; Implications for a New Theory of
Evolution.” Journal of Theoretical Biology 1985 112: 333-343.
(3) Frigaard, Niels-Ulrik et al. “Proteorhodopsin lateral gene transfer between marine
planktonic Bacteria and Archaea.” Nature 16 February 2006 439:847-850
(4) Azad, Rajeev K. and Jeffrey G. Lawrence. “Detecting laterally transferred genes: use
of entropic clustering methods and genome position.” Nucleic Acids Research 2007
35(14): 4629-4639.
(5) Boucher, Yan et al. “Lateral gene transfer and the origins of prokaryotic groups.”
Annual Review of Genetics 1 January 2003 37: 283-293.
(6) Dagan, Tal and William Martin. “Ancestral genome sizes specify the minimum rate
of lateral gene transfer during prokaryote evolution.” Proceedings of the National
Academy of Sciences of the United States of America 16 January 2007 104(3):870-875.
(7) Genereux, Diane P. and John M. Logsdon. “Much ado about bacteria-to-vertebrate
lateral gene transfer” Trends in Genetics April 2003 19(4): 191-195.