Our recent study “Diverse Molecular Mechanisms Contribute to Differential Expression of Human Duplicated Genes” was published in Molecular Biology and Evolution led by IGG grad student Colin Shew, with support from various current/former Dennis lab members Paulina Carmona-Mora, Daniela Soto, Mira Mastoras, Elizabeth Roberts, Joseph Rosas, and Gulhan Kaya and collaborator Henriette O’Geen. Using diverse functional genomic datasets, we characterized expression of recent human gene duplicates to better understand their functional fates and mechanisms underlying altered paralog expression.

Major highlights of the study:

Most human derived duplicate genes diverge in expression from their human and chimp counterparts, suggesting they’re undergoing neofunctionalization or pseudogenization.
In some cases derived genes may have usurped function of their ancestral paralogs or function through increased gene dosage.
Evolutionary age, post-transcriptional mechanisms, copy-number, and truncation status cannot completely explain observed diverged expression of genes in lymphoblastoid cell lines
ChIP-seq datasets miss most histone marks in duplicated regions that we recover using a modified bioinformatic pipeline that allows multiple read mappings.
We did not detect global differences in regulatory signatures between ancestral and derived paralogs, but rather, individual differences in cis regulatory elements, which we validate using reporter assays.