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Thursday, May 29, 2008


Telomeres are sequences at the ends of linear chromosomes that protect the essential part of the chromosome from damage following repeated rounds of DNA replication.

Because of the way DNA replication works, it is impossible to replicate both stands of parental DNA right to the very end. Consequently, after each round of DNA replication the chromosome loses a little bit of DNA and the ends get shorter and shorter.

The telomere consists of multiple copies of repetitive DNA. In the case of humans, the repeat is (TTAGGG)n where "n" is usually between 1500-2000 in germ line cells. Thus, the average telomere is about 10 kb (10,000 base pairs) in length (Riethman 2008).


Genomes & Junk DNA

Total Junk so far

After every cell division the telomere gets a little shorter so that in old individuals the average length is reduced to about 2-3 kb in most somatic cells. The original length is preserved in germ line cells.

There are 23 chromosomes in humans. If the average telomere length is about 10 kb then the total amount of TTAGGG repeats is 230 kb, or far less than 1% of the genome.1 Even if the total amount of essential sequence at chromosome ends is increased to include adjacent regions, it won't even come close to a significant percentage. Thus, while telomeric DNA is essential non-coding DNA—and not junk— it doesn't change our calculation.

UPDATE: The latest estimate of average telomere length is 8 kb corresponding to about 0.012% of the human genome [Telomere length i humans].

[Image Credit: The image shows human chromosomes labelled with a telomere probe (yellow), from Christopher Counter at Duke University.]

1. The total length in this calculation should be multiplied by 2 since there are two telomeres per chromosome.

Riethman, H. (2008) Human Telomere Structure and Biology. Annual Review of Genomics and Human Genetics 9: epub ahead of print [doi:10.1146/annurev.genom.8.021506.172017]


Anonymous said...

How does telomere length effect longer living species such as trees, turtles, bacteria, etc? I would assume that in these species longer telomeres would be favored by natural selection, but what happens when the telomeres "run out"?

Seth said...

There is a point where the telomeres do run out, and its critical that cells stop dividing (and replicating their genomes) before things go wrong. The number of times a cell can divide before stopping is termed the Hayflick limit. If something goes wrong and the cell continues to divide, the genome can become unstable.

To avoid reaching this point, some cell types produce the telomerase enzyme. This adds the repeat sequence to the ends of the chromosomes following replication. This allows cells such as embryonic stem cells and some cancers to divide continuously.

Anonymous said...

Telomeres are not the only solution to the problem of replicating the ends of linear genomes. The core of the difficulty arises by using RNA to prime DNA synthesis. Bacteriophage phi29 uses protein to prime DNA synthesis (the -OH on a Tyr residue) and can completely replicate the ends of its linear genome in this manner without telomeres. Of course, using DNA as primers in a PCR reaction works too. :)

I have never seen a good answer to why RNA can be synthesized do novo on a DNA template, but DNA cannot. I assume there must be a chemical reason for this, otherwise phages would have invented a way to do this by now.

Anyone know a reason *why* DNA synthesis requires a primer (other than "that's just the way it seems to happen")?

Seth said...

I'm certainly no expert on polyermases, but there are some differences in the contexts for RNA and DNA pol functions that might explain some of the difference. RNA polyermases identify promoter sequences to locate transcription start sites. I don't know if this holds true for all RNA pols, but the commonly used Sp6 polyermase adds its first nucleotide at the last base in the promoter sequence.

DNA polyermases generally are not being called to specific locations on a template, but are instead elongating existing molecules. The presence of double-stranded DNA adjacent to a single stranded template is thus a good cue for polymerase activity. I realize this is essentially a circular argument, "things work this way because they do." Still, that constraints on function happen to match the environments the enzymes work in isn't too shocking.

There are examples of DNA polymerases that are capable of completely ab initio synthesis, that is, without a primer/template complex. The polymerase of Thermococcus litoralis will produce up to 50 kb of repeat rich sequence with nothing but nucleotides and the appropriate reaction conditions.