Biology subjects

Shearwin-Whyatt, L.

Publications and source records attributed to Shearwin-Whyatt, L..

4 recordsLinked to original sources

bioRxiv2026

Monotremes provide novel insights into evolution of the DMRT gene family in vertebrates

Doublesex and mab-3 related (DMRT) genes encode a family of transcription factors central to sexual development across metazoa. DMRT genes are characterised by a highly conserved DNA binding domain (DM) while flanking regions may vary between species. Gene duplication and loss has shaped the diversity of the DMRT genes with several unresolved questions about their evolution. The most well characterised and conserved DMRT gene, DMRT1, functions as a sexual regulator universally in metazoans. In chicken, DMRT1 is located on the Z chromosome and acts as a dosage dependent primary sex determination gene. In therian mammals DMRT1 is autosomal, however, two copies are required for male development. Interestingly in the basal lineage of egg-laying mammals (monotremes), DMRT1 is localised on the X specific part of one of the X chromosomes. This provided the first evidence of a sex chromosome system with homology to the avian Z chromosome and raises questions about the function and evolution of DMRT1 in egg-laying mammals. To gain insight into the evolution of mammalian DMRT genes we performed sequence and expression analysis of monotreme DMRT genes and comparative analysis with other vertebrates. In monotremes, we identified DMRT genes 1-7, and show that DMRT8 is absent, suggesting that DMRT8 evolved in therian mammals after the divergence of monotremes. Sequence and expression analysis revealed multiple monotreme specific DMRT1 isoforms with additional protein-coding exons. The independent evolution of monotreme specific changes in DMRT1 may be the first indication of functional or regulatory differences in monotreme DMRT1. Article SummaryGenes in the Doublesex and mab-3 related (DMRT) family play important roles in sexual development across animals, but a comprehensive analysis of these transcription factors is lacking in the most basal mammalian lineage of monotremes. This comparative analysis of DMRT genes in monotremes and other vertebrates shows the conservation of DMRT genes 1- 7 but found no evidence of DMRT8 in monotremes or marsupial species, suggesting that this gene evolved in eutherians after the divergence of marsupials. The discovery of several monotreme specific isoforms and novel exons of the X linked DMRT1 reveals unique evolutionary changes in monotreme DMRT1.

genetics↗

bioRxiv2024

AMHY and sex determination in egg-laying mammals

The sex chromosomes of egg-laying mammals (monotremes), which lack the sex determining gene SRY1, evolved independently to those of all therian mammals2,3. Here we characterise the candidate monotreme sex determining gene, the Y-localised anti-Mullerian hormone gene (AMHY)4,3 and trace its expression during the period of sexual differentiation. Monotreme AMHX and AMHY gametologues have significant sequence divergence at the promoter, gene and protein level, likely following an original allele inversion in the common monotreme ancestor but retain conserved features of TGF-{beta} molecules. Expression of sexual differentiation genes in the echidna fetal gonad were significantly different from that of therian mammals. AMHY expression was seen exclusively in the male gonad during sexual differentiation, whereas AMHX was expressed in both sexes. Experimental ectopic expression of platypus AMHX or AMHY in the chicken embryo did not masculinise the female urogenital system, a possible result of mammalian specific changes to AMH proteins preventing function in the chicken. Our results provide fundamental insight into the first steps of monotreme sex chromosome evolution and sex determination with developmental expression data strongly supporting AMHY as the primary male sex determination gene.

evolutionary biology↗

bioRxiv2024

Pseudogenisation of NK3 Homeobox 2 (Nkx3.2) in Monotremes Provides Insight into Unique Gastric Anatomy and Physiology

Development of the vertebrate antral stomach and pyloric sphincter (antropyloric region) - involved in enzymatic breakdown and thoroughfare of food - is underpinned by a highly conserved developmental pathway involving the hedgehog, bone morphogenetic protein (BMP) and Wingless/Int-1 (Wnt) protein families. Monotremes are a unique lineage where acid-based digestion has been lost, and this correlates with a lack of genes for gastric acid and enzymes in the genomes of the platypus (Ornithorhynchus anatinus) and short-beaked echidna (Tachyglossus aculeatus). Furthermore, these species feature unique gastric phenotypes, both with truncated and aglandular antral stomachs and the platypus with no pylorus. Here, we explore the genetic underpinning of monotreme gastric phenotypes, investigating genes important in antropyloric development using the newest monotreme genome sequences (mOrnAna1.pri.v4 and mTacAcu1) together with RNA-seq data. We found that the pathway is generally conserved but, NK3 homeobox 2 (Nkx3.2) was pseudogenised in both platypus and echidna. We speculate that pyloric-like restriction in the echidna may correlate with independent evolution of Grem1 and Bmp4 sequences, and that the convergent loss of gastric acid and stomach size genotypes and phenotypes in teleost and monotreme lineages may be a result of eco-evolutionary dynamics. These findings reflect the effects of gene loss on phenotypic evolution and further elucidate the genetic control of monotreme stomach anatomy and physiology.

evolutionary biology↗

bioRxiv2023

Incomplete transcriptional dosage compensation of vertebrate sex chromosomes is balanced by post-transcriptional compensation.

Heteromorphic sex chromosomes (XY or ZW) present problems of gene dosage imbalance between the sexes, and with the autosomes. Mammalian X chromosome inactivation was long thought to imply a critical need for dosage compensation in vertebrates. However, the universal importance of sex chromosome dosage compensation was questioned by mRNA abundance measurements that demonstrated sex chromosome transcripts are neither balanced between the sexes or with autosomes in monotreme mammals or birds. Here, we demonstrate unbalanced mRNA levels of X genes in platypus males and females that correlate with differential loading of histone modifications, and confirm that transcripts of Z genes are unbalanced between males and females also in chicken. However, we found that in both species, median male to female protein abundance ratios were 1:1, implying an additional level of post-transcriptional control. We conclude that parity of sex chromosome output is achieved in birds, as well as all mammal groups, by a combination of transcriptional and post-transcriptional control, consistent with an essential role for sex chromosome dosage compensation in vertebrates.

evolutionary biology↗