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Biology subjects

Leon-Apodaca, A. V.

Publications and source records attributed to Leon-Apodaca, A. V..

2 recordsLinked to original sources

Genomic consequences of isolation and inbreeding in an island dingo population

Dingoes come from an ancient canid lineage that originated in East Asia around 8000-11,000 years BP. As Australias largest terrestrial predator, dingoes play an important ecological role. A small, protected population exists on a world heritage listed offshore island, Kgari (formerly Fraser Island). Concern regarding the persistence of dingoes on Kgari has risen due to their low genetic diversity and elevated inbreeding levels. However, whole-genome sequencing data is lacking from this population. Here, we include five new whole-genome sequences of Kgari dingoes. We analyze a total of 18 whole genome sequences of dingoes sampled from mainland Australia and Kgari to assess the genomic consequences of their demographic histories. Long (>1 Mb) runs of homozygosity (ROH) -- indicators of inbreeding -- are elevated in all sampled dingoes. However, Kgari dingoes showed significantly higher levels of very long ROH (>5 Mb), providing genomic evidence for small population size, isolation, inbreeding, and a strong founder effect. Our results suggest that, despite current levels of inbreeding, the Kgari population is purging strongly deleterious mutations, which, in the absence of further reductions in population size, may facilitate the persistence of small populations despite low genetic diversity and isolation. However, there may be little to no purging of mildly deleterious alleles, which may have important long-term consequences, and should be considered by conservation and management programs. SIGNIFICANCEA long-standing question in conservation genetics is whether long-term isolation and elevated levels of inbreeding always leads to inevitable population extinction. Here we conduct the first-ever whole-genome analysis of a population of dingoes living in long-term isolation on an island off the coast of Australia (Kgari). We show that these animals are beset by very low genetic diversity, likely the result of extensive inbreeding, and an elevated number of deleterious homozygotes. However, our results suggest that these dingoes are likely purging highly deleterious alleles, which may have allowed them to persist long term despite their extremely small population (<200 individuals).

evolutionary biology↗

Logical modeling of dendritic cells in vitro differentiation from human monocytes unravels novel transcriptional regulatory interactions

Dendritic cells are the major specialized antigen-presenting cells, thereby connecting innate and adaptive immunity. Because of their role in establishing adaptive immunity, they have been used as targets for immunotherapy. Monocytes can differentiate into dendritic cells in vitro in the presence of colony-stimulating factor 2 (CSF2) and interleukin 4 (IL4), activating four signalling pathways (MAPK, JAK/STAT, NFKB, and PI3K). However, the transcriptional regulation responsible for dendritic cell differentiation from monocytes (moDCs) remains unknown. By curating scientific literature on moDCs differentiation, we established a preliminary logical model that helped us identify missing information for the activation of genes responsible for this differentiation, including missing targets for key transcription factors (TFs). Using ChIP-seq and RNA-seq data from the Blueprint consortium, we defined active and inactive promoters, together with differentially expressed genes in monocytes, moDCs, and macrophages (which correspond to an alternative cell fate). We then used this functional genomic information to predict novel targets for the identified TFs. We established a second logical model integrating this information, which enabled us to recapitulate the main established facts regarding moDCs differentiation. Prospectively, the resulting model should be useful to develop novel immunotherapies based on moDCs regulatory network.

immunology↗