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Milhaven, M.

Publications and source records attributed to Milhaven, M..

2 recordsLinked to original sources

Interpreting patterns of X chromosomal relative to autosomal diversity in aye-ayes(Daubentonia madagascariensis)

We here present high-quality, population-level sequencing data from the X chromosome of the highly-endangered aye-aye, Daubentonia madagascariensis. Using both polymorphism- and divergence-based inference approaches, we quantify fine-scale mutation and recombination rate maps, study the demographic and selective processes additionally shaping variation on the X chromosome, and compare these estimates to those recently inferred from the autosomes in this species. Results suggest that an equal sex ratio is most consistent with observed patterns of variation, and that no sex-specific demographic patterns are needed to fit the empirical site frequency spectrum. Further, reduced rates of recombination were observed relative to the autosomes as would be expected, whereas mutation rates were inferred to be similar. Utilizing the estimated population history together with the mutation and recombination rate maps, we evaluated evidence for both recent and recurrent selective sweeps as well as balancing selection across the X chromosome, finding no significant evidence supporting the action of these episodic processes. Overall, these analyses provide new insights into the evolution of the X chromosome in this species, which represents one of the earliest splits in the primate clade.

evolutionary biology↗

Co-option of the gibbon-specific LAVA retrotransposon in DNA repair pathways

Co-option of transposable elements (TEs) to become part of existing or new enhancers is an important mechanism for evolution of gene regulation. However, contributions of lineage-specific TE insertions to recent regulatory adaptations remain poorly understood. Gibbons present a suitable model to study these contributions as they have evolved a lineage-specific TE called LAVA, which is still active in the gibbon genome. The LAVA retrotransposon is thought to have played a role in the emergence of the unusually rearranged structure of the gibbon genome by disrupting transcription of cell cycle genes. In this study, we investigated whether LAVA may have also contributed to the evolution of gene regulation by adopting enhancer function. We characterized fixed and polymorphic LAVA insertions across multiple gibbons and found 96 LAVA elements overlapping enhancer chromatin states. Moreover, LAVA was enriched in multiple transcription factor binding motifs, was bound by an important transcription factor (PU.1), and was associated with higher levels of gene expression in cis. We found gibbon-specific signatures of purifying/positive selection at 27 LAVA insertions. Two of these insertions were fixed in the gibbon lineage and overlapped with enhancer chromatin states, representing putative co-opted LAVA enhancers. These putative enhancers were located within genes encoding SETD2 and RAD9A, two proteins that facilitate accurate repair of DNA double-strand breaks and prevent chromosomal rearrangement mutations. Thus, LAVAs co-option in these genes may have influenced regulation of processes that preserve genome integrity. Our findings highlight the importance of considering lineage-specific TEs in studying evolution of novel gene regulatory elements.

evolutionary biology↗