Diverse Cis-Regulatory Mechanisms Contribute to Expression Evolution of Tandem Gene Duplicates

Abstract

Pairs of duplicated genes generally display a combination of conserved expression patterns inherited from their unduplicated ancestor and newly acquired domains. However, how the cis-regulatory architecture of duplicated loci evolves to produce these expression patterns is poorly understood. We have directly examined the gene-regulatory evolution of two tandem duplicates, the Drosophila Ly6 genes CG9336 and CG9338, which arose at the base of the drosophilids between 40 and 60 Ma. Comparing the expression patterns of the two paralogs in four Drosophila species with that of the unduplicated ortholog in the tephritid Ceratitis capitata, we show that they diverged from each other as well as from the unduplicated ortholog. Moreover, the expression divergence appears to have occurred close to the duplication event and also more recently in a lineage-specific manner. The comparison of the tissue-specific cis-regulatory modules (CRMs) controlling the paralog expression in the four Drosophila species indicates that diverse cis-regulatory mechanisms, including the novel tissue-specific enhancers, differential inactivation, and enhancer sharing, contributed to the expression evolution. Our analysis also reveals a surprisingly variable cis-regulatory architecture, in which the CRMs driving conserved expression domains change in number, location, and specificity. Altogether, this study provides a detailed historical account that uncovers a highly dynamic picture of how the paralog expression patterns and their underlying cis-regulatory landscape evolve. We argue that our findings will encourage studying cis-regulatory evolution at the whole-locus level to understand how interactions between enhancers and other regulatory levels shape the evolution of gene expression.

Skeletal Mineralization in Association with Type X Collagen Expression Is an Ancestral Feature for Jawed Vertebrates

“…Tandem duplication of type X collagen genes in chondrichthyan lineage was consequently followed by subfunctionalization of tandem duplicates. This process most probably required diversification of cis-regulatory mechanisms (Baudouin-Gonzalez et al. 2017).…”

Mechanisms of enhancer action: the known and the unknown

“…If the duplicated region was a cis-regulatory module, it evolves new regulatory functions over time, resulting in the genesis of new enhancers [ 52 , 53 ]. In a related scenario, when a CRE-coupled-gene module is duplicated, both the resultant CREs develop specializations such that the paralogs are regulated differently [ 54 , 55 ]. Additionally, TFBSs can be created de novo in an inert sequence, which can evolve over time into an enhancer.…”

Horizontal Gene Transfer and Gene Duplication of β-Fructofuranosidase Confer Lepidopteran Insects Metabolic Benefits

“…Gene duplication is a major evolutionary mechanism that can contribute genomes with the raw material for new or altered gene functions ( Zhang 2003 ; Marques et al. 2008 ; Farre and Alba 2010 ; Baudouin-Gonzalez et al. 2017 ; Leite et al.…”

“…2019 ). Harmful mutations occur more frequently than beneficial ones; hence, one copy may accumulate deleterious mutations, and eventually become a nonfunctional pseudogene ( Baudouin-Gonzalez et al. 2017 ; Zhou et al.…”