Archive for July 30th, 2007
Copy number variations throughout 60 million years of human and primate evolution
I’ve covered copy number variations in the past, and the post I put up this morning is kinda along the same lines as the following paper I will introduce. But, in a nutshell, this one is a comparison of copy number variation or CNVs in primate genomes.
CNV is a term used in genomic studies to describe the amount of copies of a particular gene in a particular genotype. Copy number variations are a type of polymorphism that can come about from transposons and restructuring of genomes due to Alu elements. Sometimes changes in CNVs imply that genes have been positively or negatively selected for.
In the new report, soon to be available in Genome Research, the results of a large-scale, genome-wide study to investigate gene copy number differences among ten primate species, including humans have been published. The study, “Gene copy number variation spanning 60 million years of human and primate evolution,” will be online tomorrow and is the most comprehensive research on gene copy number variation across human and non-human primate species so far. It provides an overview of genes and gene families that have undergone major copy number expansions and contractions in different primate lineages spanning approximately 60 million years of evolutionary time.
Dr. James Sikela and team used microarrays with over 24,000 human genes to screen and compare genomic hybridization. In other words, they compared DNA samples from humans to those of nine other primate species: chimpanzee, gorilla, bonobo, orangutan, gibbon, macaque, baboon, marmoset, and lemur in oder to identify specific genes and gene families that, through evolutionary time, have undergone lineage-specific copy number gains and losses.
The authors of the report suggest that,
“many of the genes identified are likely to be important to lineage-specific traits found in humans and in the other primate lineages surveyed.”
Several gene families that exhibited striking lineage-specific differences were highlighted. In particular, the human lineage-specific copy number expansion of a gene called AQP7, a gene that plays a role in transporting water and glycorol across membranes, was pointed out because it could explain why humans have evolved the capacity for endurance running. It may facilitate the mobilization of energy stores during long periods of intense exercise as well as playing a role in dissipating excess heat through sweating. I’ll have more on this tomorrow, when I get access to the paper but the other findings included dramatic gene copy number differences potentially associated with cognition, reproduction, immune function, and susceptibility to genetic disease. Read the rest of this entry »
Finding parallel genetic variation of ACE activity in baboons and humans
Yann has found some interesting papers in the last day or so. One paper he stumbled upon researches the heritable variation of Angiotensin Converting Enzyme (ACE) in humans and baboons. It is titled, Parallel effects of genetic variation in ACE activity in baboons and humans.” 
ACE is a homeostatic regulator protein, and like other physiological phenotypes, it varies a lot in humans. Proteins that vary a lot are important to research because they help explain how we see so much variation in human populations.
The variation in ACE is attributed with an Alu insertion-deletion polymorphism in the ACE gene. Since I don’t know if you have heard of Alu elements, I’ll explain to you what I know of them. Much of the human genome, and as we are now finding out much of primate genomes, have a lot of transposable elements in them. Transposable elements are segments of DNA that jump around, copy, and rearrange themselves. This genetic versatility facilitates lots of diversity, variation, and potential for selective processes.
Alu elements are classified as a type of transposon where copy is made of RNA, not DNA. This is more specifically called a retrotransposon. Short interspersed elements (SINEs) are about ~300 nucleotides in length and are an even more specific type of retrotransposon . The most abundant type of SINE are Alus. More than 1 million Alus are found in the human genome and make up about 10% of the genome. I found a paper announcing the creation of a database specific to Alu elements in the human genome, but the link to the database doesn’t seem to work. Oh well.
If you want to read more about Alus check out this review article but for your sanity’s sake I’ll wrap up the review of Alu elements… Because Alus are more or less mobile they are important because they affect gene structures, protein sequences, splicing motifs and expression patterns.
You’re probably wondering what was concluded from the comparison of the ACE in humans and baboons? From the abstract,
“We identified a similar Alu insertion-deletion polymorphism in the baboon ACE homologue and measured its frequency in a wild population and a captive population of baboons. We also analyzed the contribution of ACE genotype at this indel to variation in serum ACE activity in the captive population. When conditioned on weight, a known factor affecting ACE activity in humans, age and ACE genotype both accounted for variance in ACE activity; in particular, we identified a significant nonadditive interaction between age and genotype…. These results demonstrate an interesting parallel between the genetic architecture underlying ACE variation in humans and baboons, suggesting that further attention should be paid in humans to the relationship between ACE genetic variation and aging.”
Go figure, ACE, a homeostatic regulator protein, has something to do with aging. And the variation, the amount of Alu element restructuring of ACE has a correlation to how long or short humans and baboons live. Interesting.
More fun reading on the subject:
