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Transcriptome Variation Patterns Show How Organ Site, Species Influence Expression of Some Genes

COLD SPRING HARBOR, NY (GenomeWeb) – By characterizing the RNA-seq profiles of various organs from a range of species, Alessandra Breschi from the Center for Genomic Regulation in Barcelona found that the expression of some genes cluster by species while the expression of others cluster by organ type. Those genes whose activity varied by species and not by organ were more likely to be housekeeping genes, she added.

As Breschi noted during a Biology of Genomes presentation here this week, mice and other organisms are commonly used as model systems, but it has been unclear whether transcriptional profiles are more conserved across species or across organ types.

"Would a human liver be closer to a mouse liver or a human heart?" Breschi asked.

To examine this, she turned to a set of six organs from seven species, encompassing some 6,000 protein-coding genes with one-to-one orthologs. By then studying transcriptome variation both by species and by organ, Breschi and her colleagues found that about a quarter of genes had high variation among organs and low variation among species, while another quarter had the reverse, though they all fell along a continuum.

Genes whose expression varied between organs but not between species drive evolutionary constraint, Breschi noted, while genes whose expression varies across species, but not tissues, are linked to tissue definition. Further, she added that genes with high relative variation among species and low among organs were enriched for gene ontology terms related to housekeeping functions.

In addition, she noted that genes whose expression varied across species were marked by less sequence conservation at the exon level and at transcription start sites.

Further, genes with higher variation across species had greater numbers of CpG islands at their transcription start sites. In mouse livers, Breschi and her colleagues found that genes that vary highly by species have higher levels of promoter methylation, and they noted the effect seemed to hold across organ types, including cerebellum, heart, kidney, and testes.

Genes with high variation among organs and low variation among species were also enriched for GO terms linked with diseases and cancer types, she noted.

Knowing whether the expression of a particular gene or group of genes is conserved by species or by organ type could also inform model system-based studies.

"Decomposing variation in gene expression is essential in order to identify those genes — that vary across tissues, but not across species — in which mouse is a good model for human biology," the talk abstract noted.