Researchers have uncovered genetic elements that drive the rapid development of marsupials’ facial features.
The study in fat-tailed dunnarts, native to Australia, is published today in eLife as the final Version of Record after appearing previously as a Reviewed Preprint. The editors describe it as important work with compelling data, including a new dunnart genome assembly, which they say provide an “invaluable reference” for future mammalian evolution studies.
An adult female fat-tailed dunnart (Sminthopsis crassicaudata) carrying four young ones. Image credit: Cook et al. (CC BY 4.0)
Marsupials and placental mammals differ significantly in their reproduction and growth patterns. While marsupials are born highly underdeveloped after a short gestation period and complete their development inside the maternal pouch, placental mammal foetuses develop fully inside the uterus. When compared to placental mammals, marsupials show accelerated orofacial (mouth and face) development relative to their central nervous system, reflecting the functional demands after birth.
Cis-acting regulatory elements – DNA regions that regulate the expression of neighbouring genes – have been proposed to play a significant role in differences in mammalian facial development. But no studies have previously attempted to compare the overall gene regulatory landscape between marsupials and placentals at the same point in development.
“Such studies can provide functional insights into how regulatory elements in the genome control craniofacial development across mammals, and consequently the evolutionary changes that have driven divergent growth patterns in marsupials and placentals,” explains first author Laura Cook, who undertook this work as a PhD candidate at the School of BioSciences, University of Melbourne, Australia, and is now a Postdoctoral Researcher at Lawrence Berkeley National Laboratory, US.
“Having previously described the accelerated orofacial development in the fat-tailed dunnart, a tiny marsupial with just a 13-day gestation, we wanted to see how the regulation of genes driving early facial development in marsupials differs from those in placental mammals like the mouse.”
To do this, Cook and the team used two sequencing techniques – ChIP-sequencing (ChIP-seq) and RNA-sequencing (RNA-seq) – on craniofacial tissue from newborn dunnart pouch young. The tissue was collected from the frontal region of the face and nose (fronto-nasal tissue), mandibular (relating to the lower jaw) and maxillary prominences (relating to the upper jaw, upper lip and cheeks).
Applying the sequencing methods to this tissue enabled the team to perform a detailed characterisation of chromatin marks – chemical modifications on DNA that regulate gene expression – during the dunnarts’ early craniofacial development. They then examined the similarities and differences in two chromatin modifications associated with cis-regulatory elements (H3K4me3 and H3K27ac) between the dunnart and mouse, and incorporated comparisons of gene expression between species. For the comparisons, they used publicly available craniofacial ChIP-seq data for H3K4me3 and H3K27ac generated by the mouse ENCODE consortium, spanning multiple developmental time-points.
Their analyses revealed that genes involved in regulating facial development are largely conserved in both the mouse and dunnart, but their cis-regulatory elements vary significantly. In particular, they discovered dunnart-specific regulatory elements near highly-expressed genes that are either lowly or not expressed at all in the mouse. These genes are related to three main developmental processes: skin/epidermis development, muscle development and contraction, and sensory system development.
“The recurrence of genes related to the development of the dunnarts’ sensory systems highlights a unique aspect of early pouch life in marsupials – the challenge of reaching it,” says co-senior author Irene Gallego Romero, Associate Professor at St Vincent’s Institute of Medical Research, Melbourne, Australia. “Newborn marsupial young need their sensory systems, especially their sense of smell, to be highly developed – and quickly – so they can follow the cues that guide them to their mother’s pouch where they will finish developing.”
“Together, the data from our experiments suggest that accelerated craniofacial development in dunnarts may be driven by enhancer activity that has evolved specifically to support their postnatal survival,” adds Andrew Pask, Professor of Genetics & Developmental Biology at the School of BioSciences, University of Melbourne. “This work highlights the power of marsupial–placental comparative genomics for understanding the role of enhancers in driving different growth strategies between species.”
A notable limitation of the study is that it does not include multiple postnatal stages of the dunnart, due to the limited availability of the pouch young. The authors say they now hope to expand the work to more developmental stages in future studies to provide additional insights. “We also plan to apply single-cell, multi-modal technologies to dunnart tissues in future studies to investigate the specific regulatory differences between their central nervous system and orofacial development,” Pask concludes.
Accompanying images for this work are available here.
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