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Bautista, R.

Publications and source records attributed to Bautista, R..

2 recordsLinked to original sources

Ghost admixture in eastern gorillas

Archaic admixture has had a significant impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. Within the great apes archaic admixture has been identified in chimpanzees and bonobos, but the possibility of such events has not been explored in other species. Here, we address this question using high-coverage whole genome sequences from all four extant gorilla subspecies, including six newly sequenced eastern gorillas from previously unsampled geographic regions. Using Approximate Bayesian Computation (ABC) with neural networks to model the demographic history of gorillas, we find a signature of admixture from an archaic ghost lineage into the common ancestor of eastern gorillas, but not western gorillas. We infer that up to 3% of the genome of these individuals is introgressed from an archaic lineage that diverged more than 3 million years ago from the common ancestor of all extant gorillas. This introgression event took place before the split of mountain and eastern lowland gorillas, likely more than 40 thousand years ago, and may have influenced perception of bitter taste in eastern gorillas. When comparing the introgression landscapes of gorillas, humans and bonobos, we find a consistent depletion of introgressed fragments on the X chromosome across these species. However, depletion in protein-coding content is not detectable in eastern gorillas, possibly as a consequence of stronger genetic drift in this species.

evolutionary biology↗

ATR-I774Yfs*5 promotes genomic instability through micronuclei formation

Although mismatch repair (MMR) defects are associated with high risk of malignancy, the specific oncogenic drivers pertinent to MMR-affected cancers are poorly characterized. The heterozygous ATR-I774Yfs*5 mutation, the result of strand slippage in a poly-A tract of the Ataxia Telangiectasia and Rad3 related (ATR) gene, is overexpressed in MMR-defective malignancies including colorectal carcinoma (CRC) and is the most common ATR mutation in cancer. Here, we explore the contribution of ATR-I774Yfs*5 to genomic integrity. Using heterozygous ATR-I774Yfs*5 HCT-116 cells to mimic the native mutation, we found this mutation reduced ATR activity as measured by damage-induced Chk1 phosphorylation at S317 and ATR autophosphorylation ATR at T1989. ATR-I774Yfs*5 expression impaired genomic stability as visualized by the appearance of micronuclei in two stable expression models as well as in cell lines transfected with ATR-I774Yfs*5. Micronucleus development was dependent on replication and independent of ATR copy number. ATR-I774Yfs*5 expression did not alter cellular viability, cell cycle progression, or replicative rate, suggesting this mutation is well-tolerated despite its destabilizing effect on the genome. Taken together, these data suggest that the ATR-I774Yfs*5, whose development is favored in the context of MMR deficiency, may represent an important driver of a mutator phenotype by promoting genomic instability.

cancer biology↗