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The Myth of Junk DNA. Dr. Raymond G. Bohlin Fellow, Discovery Institute Probe Ministries. Non-Protein Coding DNA. 2001 – 65,000 mRNAs, but only 4% from exons 2002 – ENCODE found 11,655 non-protein-coding RNAs 2005 – most of mammalian DNA is transcribed - PowerPoint PPT Presentation
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The Myth The Myth of Junk of Junk DNADNA
Dr. Raymond G. BohlinFellow, Discovery InstituteProbe Ministries
Non-Protein Coding DNA 2001 – 65,000 mRNAs, but only 4% from
exons 2002 – ENCODE found 11,655 non-
protein-coding RNAs 2005 – most of mammalian DNA is
transcribed 2008 – both strands used in
transcription and frequently from overlapping segments
Evolutionary predictions If a sequence is non-functional, then
over time the sequence should degrade
If a sequence is functional, then the sequence should be conserved by natural selection.
Non-Protein-coding DNA 2005 – non-coding regions in humans
and mice, hundreds of nucleotides long are identical.
Such ultra conserved regions (UCR) regulate developmentally important functions
This is not expected by evolution!
Introns Introns are not just inert spacers
between exons 2005 – intronic sequence is highly
conserved between humans, mice, rats, dogs and chickens – likely functional
Mammalian thyroid receptor gene produces two variant proteins with opposite effects – splicing is regulated by an intron.
Co-expressed loci are clustered together along in the Co-expressed loci are clustered together along in the nucleus, sometimes to “create” genesnucleus, sometimes to “create” genes
Chromosome 2 loop
Chromosome 21 loop
Chromosome 5 loop
Nuclear compartmentwith concentrated
transcription factors
Pseudogenes A pseudogene is a gene that closely
resembles a functional gene but appears to be a useless leftover
Pseudogenes as defined above would be predicted by evolution but difficult under ID
The human genome may have as many as 2000 pseudogenes
pseudogenes Some pseudogenes appear to suppress
expression of the functional gene. The pseudogene can be transcribed and
this transcript binds to the mRNA sequence of the functional gene, thus blocking translation. “RNA interference”
Transcribed pseudogenes serve as “perfect decoys” for RNA degrading enzymes, thus enhancing expression.
Repetitive Sequences About half of the mammalian genome
consists of various types of repetitive sequences.
Long Interspersed Nuclear Elements – LINEs
Short Interspersed Nuclear Elements – SINEs
Endogenous Retroviruses - ERVs
Overview of LINEsLINEs and SINEs have different structural arrangements. The major LINE in the human
genome is the L1. This sequence: Is found throughout Mammalia but is largely taxon-specific Is variously truncated at the 5’ end: ranges from 6-8kb to a few hundred bps in length Has a biased chromosomal distribution: AT-rich chromosome bands and the X-chromosome
(A-rich ‘tail’)
Species-specificregulatory region
ORF1ORF2: Reverse transcriptase
and endonuclease
G-densePu:Py
element
3’ UTR
(A-rich ‘tail’)
Chimp- vs. Human-Specific L1s*C
him
p
Hum
an
271 L1Hs(Ta) elements 252 L1 nonTa elements 490 L1Pa2 elements
0 L1Hs(Ta) elements 210 L1 nonTa elements 476 L1Pa2 elements
5-6 Million Years Ago
*Mills, R.E. et al. 2006. Recently mobilized transposons in the human and chimpanzee genomes. Am. J. Hum. Genet. 78: 671-679.
Remember the layout of a mammalian gene? Many human gene folders are bordered by species-specific repertoires of L1s.
“Gene” 1
“Gene” 2
“Gene” 3 “Gene” 5
“Gene” 4
RNA outputs
L1s L1s
Almost forty percent Almost forty percent of human nuclear of human nuclear matrix attachment matrix attachment elements are L1 elements are L1 sequencessequences.
Overview of SINEs
The major SINE in the human genome is Alu. Unlike LINE-1, Alu (and other SINEs) do not encode enzymes for their mobilization. This sequence:
Is primate-specific—subfamilies are distributed in a taxonomically hierarchical manner (same with LINE-1)
Is ~300 bps in length; consists largely of two dimers (with sequence differences)
Has a biased genomic distribution: GC-rich chromosome bands
(A-rich ‘tail’)
Monomer A
CentralA-stretch
31 bpinsert
Monomer B
Chimp- vs. Human-Specific SINEs*C
him
p
Hum
an864 SVA (SINE) elements 396 SVA (SINE) elements
5-6 Million Years Ago
263 AluS elements 1,709 AluYa5 elements 1,290 AluYb8 elements
484 AluY elements
356 AluYc1 elements 261 AluYg6 elements
50 AluS elements 10 AluYa5 elements 9 AluYb8 elements
360 AluY elements
979 AluYc1 elements 1 AluYg6 elements
1167 other Alu elements 233 other Alu elements
*Mills, R.E. et al. 2006. Recently mobilized transposons in the human and chimpanzee genomes. Am. J. Hum. Genet. 78: 671-679.
Any seemingly random aspect of chromosome sequence arrangement is not. A case in point involves endogenous retroviruses (ERVs):
A. Human ERVs contribute 51,197 promoter elements that initiate transcription at various stages (Conley et al., Bioinformatics 24: 1563-1567, 2008).B. Mouse ERVs are highly expressed at the 2-cell embryo stage (and are the earliest to be transcribed in the zygote) and are essential for ontogenesis (Kigami et al., Biology of Reproduction 68: 651-654, 2003).
ERVs In humans ERVs help regulate blood cell
production and metabolizing fat ERVs also regulate gene expression in
the gastrointestinal tract, mammary glands, and testes.
The ERV derived protein syncitin is required for the fusion of fetal and maternal cells in the placenta.
Although less than 2% of genomic DNA in many Although less than 2% of genomic DNA in many vertebrates (e.g., mammals) can be placed in the vertebrates (e.g., mammals) can be placed in the traditional “gene” category, nearly all sequences are traditional “gene” category, nearly all sequences are transcribed in a cell- and tissue-specific manner.transcribed in a cell- and tissue-specific manner.
DNA as Computer Information carried by DNA is
bidirectional, multi-layered, and interleaved.
Repetitive elements format and punctuate the information at different scales
Cells can write codes onto non-coding DNA so phenotype is not always equal to genotype
“metaprogramming” – Cornell Conf.