NEW YORK (GenomeWeb News) – In a paper scheduled to appear online this week in the Proceedings of the National Academy of Sciences, researchers from the Genome Institute of Singapore and Wayne State University used a genome-wide screen to try to fish out primate-specific sequences in the human genome.
Their search uncovered more than 100 transcriptional units that appear to be specific to primates, based on sequence comparisons involving several primate and non-primate genomes. By looking at the conservation, structure, and expression of these transcriptional units, the researchers were able to identify patterns that provide a glimpse into primate evolution — and set the stage for more comprehensive studies of the function of these and other primate-specific genes.
Despite the dramatic increase in DNA sequence information available over the past few years, researchers are still trying to tease apart which sequences and genome features lead to human- and primate-specific traits. Some previous studies suggest human genomes contain inactivated versions of genes used by other primates. Other studies have identified duplications, rearrangements, and new genes that appear to have cropped up during primate evolution.
"Although factors such as segmental duplications and positive selection have received much attention as potential drivers of primate phenotypes, single-copy primate-specific genes are poorly characterized," senior author Leonard Lipovich, a genetics researcher affiliated with the Genome Institute of Singapore and Wayne State University, and his co-authors noted.
In an effort to rectify this, the researchers weeded through human complementary DNA and expressed sequence tag data to come up with 38,037 human transcriptional units. They then searched for these transcriptional units in the genomes of nine other animals to determine which, if any, were specific to the primate lineage.
Using this approach, the team found 131 transcriptional units that appear to be primate specific. Most of these were detected in all of the primate genomes evaluated, but absent in the non-primate genomes.
More than 90 percent of the primate-specific transcriptional units had interspersed repeat-containing exons. And almost half of the units — about 46 percent — seem to code for proteins.
The team found other patterns as well. For example, they noted that the primate-specific transcriptional units frequently contained just one exon.
"Intronless genes can arise from retroposition," the authors explained, "which intensified in primates 38 to 50 [million years ago]. Alternatively, the 'introns-late' model, implying intron accretion over evolutionary time, may explain why young [transcriptional units] are unspliced or have fewer exons than older conserved genes."
On the other hand, just a quarter of the primate-specific sequences came from sub-telomeric or pericentromeric parts of the genome — regions involved in segmental duplications.
When the researchers examined the expression patterns for proposed primate-specific genes using information from GenBank, they found that many of the transcripts were expressed in brain and reproductive tissues. But, they noted, "only reproductive, not neuronal expression was enriched."
The team found other ties to reproduction as well: they noted that 21 of the 33 transcriptional units represented on the Affymetrix U122 microarray were differentially expressed in sperm from men with an infertility problem called teratozoospermia compared with sperm from fertile men.
Overall, the researchers concluded that primate-specific transcripts — including protein-coding and long non-coding RNA sequences — have contributed to the evolution of reproduction and disease in the primate lineage. In the future, they say, additional research is needed to find additional primate-specific genes and to clarify their functional roles.