New theory about human genome evolution - tracking 'stealth' DNA elements

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New theory about human genome evolution - tracking 'stealth' DNA

elements

01 Jul 2005 Medical News Today

A group of LSU researchers, led by biological sciences Professor Mark

Batzer, have unraveled the details of a 25-million-year-old

evolutionary process in the human genome. Their study focused on the

origin and spread of transposable elements in the genome, many of

which are known to be related to certain genetic disorders, such as

hemophilia.

" Effectively, we've devised a theory that allows us to explain the

origin of about half of all of the human genome, " said Batzer.

Batzer was the principal investigator on the study, while LSU

biological sciences graduate students Kyudong Han and Jinchuan Xing

were the co-authors of the Genome Research paper on the discoveries.

Other contributors to the research included graduate students Hui

Wang and Dale Hedges, along with postdoctoral fellows Randall Garber

and Cordaux. Their findings were recently published in the

journal Genome Research.

Batzer, the C. Kent Professor of Life Sciences in the

Department of Biological Sciences at LSU, and his group found that

specific DNA sequences that appear to be in an inactive state for

long periods of time may not be simply lying dormant after all.

Instead, Batzer and his team have discovered that these elements

played a crucial role in human evolution by secretly spawning

hyperactive copies, giving rise to the most abundant family of

transposable elements in the human genome, known as Alu elements. The

study provides the first strong evidence for the evolution of Alu

elements to date.

Alu elements are short DNA sequences capable of copying themselves,

mobilizing through an RNA intermediate and inserting into another

location in the genome. Over evolutionary time, this activity, known

as " retrotransposition, " has led to the generation of more than one

million copies of Alu elements in the human genome, making them the

most abundant type of sequence present. Because Alu elements are so

abundant, comprising approximately 10 percent of the total human

genome, they have been thoroughly examined and characterized in terms

of their origin and sequence composition. What has remained elusive

to scientists, however, is how these elements persist and propagate

over time and influence human evolution. In an attempt to understand

this process, Batzer and his colleagues examined a sub-family of Alu

elements in the human genome known as the AluYb lineage, and compared

these elements to those in the genomes of other primate species,

including chimpanzees, bonobos, gorillas, orangutans, gibbons and

siamangs. The AluYb sub-family accounts for approximately 40 percent

of all human-specific Alu elements and is currently one of the most

active Alu lineages in the human genome. Some AluYb elements are

still actively mobilizing in the human genome, causing insertion

mutations that have led to the development of a number of inherited

diseases.

" These elements have contributed quite a bit to the diversity of

human and non-human primate genomes, so it is very important to

understand their origin and spread, " said Batzer. " They cause about

half a percent of all human genetic disorders. "

According to Batzer, some of the genetic disorders related to these

elements include hemophilia and some cancers. These disorders are

caused by insertional mutation or by recombination between these

elements, which is when elements that are near each other undergo

a " recombination " and part of the genome is deleted in the process.

Batzer's team demonstrated that the AluYb linage dates back

approximately 18-25 million years. Their results also indicated that

the AluYb sub-family underwent a major species-specific expansion in

the human genome during the past 3-4 million years. This apparent 20-

million-year stretch of general inactivity, followed by a sudden

outburst of human-specific retrotransposition activity in the past

few million years, led Batzer and colleagues to formulate a new

theory for the evolution of Alu elements, termed the " stealth driver "

model. In the " stealth driver " model, low-activity Alu elements are

maintained in low-copy number for long periods of time and

occasionally produce short-lived hyperactive progeny that contribute

to the formation and expansion of Alu elements in the human genome.

Batzer explained that the exact purpose or function of these elements

is still debated, but understanding their basic behavior and history

could be crucial to finding answers in the future.

" Mobile elements make up a huge proportion of the human genome and

understanding how these elements spread through the genome and how

they contribute to genetic diversity is critical, " said Batzer. " This

research provides a fundamental insight into their spread and it has

changed our opinion about what it takes to successfully spread

through the genome. "

More information can befound on the Batzer Laboratory Web site at

http://batzerlab.lsu.edu.

The Web site for Genome Research is www.genome.org. Genome Research

is an international, monthly, peer-reviewed journal published by Cold

Spring Harbor Laboratory Press.

It is one of the five most highly cited primary research journals in

genetics and genomics.

http://www.lsu.edu