Cis-regulatory evolution integrated the Bric-à-brac transcription factors into a novel fruit fly gene regulatory network

Abstract

Gene expression evolution through gene regulatory network (GRN) changes has gained appreciation as a driver of morphological evolution. However, understanding how GRNs evolve is hampered by finding relevant cis-regulatory element (CRE) mutations, and interpreting the protein-DNA interactions they alter. We investigated evolutionary changes in the duplicated Bric-à-brac (Bab) transcription factors and a key Bab target gene in a GRN underlying the novel dimorphic pigmentation of D. melanogaster and its relatives. It has remained uncertain how Bab was integrated within the pigmentation GRN. Here we show that Bab gained a role in sculpting sex-specific pigmentation through the evolution of binding sites in a CRE of the pigment-promoting yellow gene and without any noteworthy changes to Bab protein coding sequences. This work demonstrates how a new trait can evolve by incorporating existing transcription factors into a GRN through CRE evolution, an evolutionary path likely to predominate newly evolved functions of transcription factors.

Genetic switch in UV response of mimicry-related pale-yellow colors in Batesian mimic butterfly, Papilio polytes

“…This indicates that these genes are usually repressed by dsx (H) in mimetic female wings, which are comparable to the following reports. A recent study on Drosophila melanogaster reported that in females, a female-specific dsx isoform and Abdominal-B (Abd-B) activates bric-a brac (bab) expression, whereas in males, a male-specific dsx isoform represses bab, which allows for the expression of pigment synthesis genes, yellow and tan (43). In butterflies, it is known that melanin synthesis genes such as DDC and yellow regulate both the pigment and morphology of wing scales, while ebony affects coloration (44).…”

Tissue-specific versus pleiotropic enhancers within thebric-a-bractandem gene duplicates display differential regulatory activity and evolutionary conservation

“…Bab1-2 proteins are co-expressed in many tissues (11, 12). In the developing abdominal epidermal cells, within so-called histoblast nests, they jointly regulate directly yellow expression in a sexually-dimorphic manner, thus controlling adult male versus female body pigmentation traits (13–16). bab1 - 2 co-expression in the developing epidermal histoblast nests is partially governed by two CREs which drive reporter gene expression (i) in a monomorphic pattern in the abdominal segments A2-A5 of both sexes (termed AE, for “ A nterior E lement”), and (ii) in a female-specific pattern in the A5-A7 segments (DE, for “ D imorphic E lement”) (Fig 1A) (14, 17).…”

“…bab1 - 2 co-expression in the developing epidermal histoblast nests is partially governed by two CREs which drive reporter gene expression (i) in a monomorphic pattern in the abdominal segments A2-A5 of both sexes (termed AE, for “ A nterior E lement”), and (ii) in a female-specific pattern in the A5-A7 segments (DE, for “ D imorphic E lement”) (Fig 1A) (14, 17). In addition to controlling male-specific abdominal pigmentation traits, bab1 - 2 are required, singly, jointly or in a partially-redundant manner, for embryonic cardiac development, sexually-dimorphic larval somatic gonad formation, salivary glue gene repression, female oogenesis, wing development as well as distal leg (tarsal) and antennal segmentation (11, 13, 17–24). In addition to abdominal AE and DE, two other bab enhancers, termed CE and LAE (see Fig 1A), have been characterized, which recapitulate bab2 expression in embryonic cardiac cells and developing tarsal as well as distal antennal cells, respectively (17, 21, 25).…”

“…While both bab genes are required for dimorphic abdominal pigmentation traits and somatic gonad specification (13, 22), only bab2 is critical for tarsal segmentation (11). While bab1 loss-of-function legs are apparently wild-type, a null allele ( bab AR07 ) removing bab2 (and bab1 ) activities causes segmental transformation along the P-D leg axis, notably sex comb teeth in tarsal segments ts2-3 of male forelegs, normally only found in ts1, as well as ts2-5 tarsal fusions in both genders (11).…”

Modular cis‐regulatory logic of yellow gene expression in silkmoth larvae

“…Previous studies have closely investigated the cis ‐regulatory regions of pigmentation genes in Diptera and have demonstrated their cis ‐regulatory modularity (Wittkopp, ; Rebeiz and Willams, ). In particular, the yellow gene of Drosophila and its cis ‐regulatory region have been used as a model system for identification, functional evolution, and connection to an evolving trans ‐landscape of a pleiotropic gene (Gompel et al ., ; Jeong et al ., ; Prud’homme et al ., ; Werner et al ., ; Ordway et al ., ; Camino et al ., ; Roeske et al ., ). The modularity of gene regulation is thought to avoid pleiotropic constraints in evolutionary divergence (Stern, ; Davidson, ; Carroll et al ., ; Carroll, ; ; Wittkopp, ; Wray, ; Stern and Orgozozo, ).…”