Biology subjects

Del Carpio, C. A.

Publications and source records attributed to Del Carpio, C. A..

3 recordsLinked to original sources

bioRxiv2024

Evolutionary consequences of domestication on the selective effects of new amino acid changing mutations in canids

The domestication of wild canids led to dogs no longer living in the wild but instead residing alongside humans. Extreme changes in behavior and diet associated with domestication may have led to the relaxation of the selective pressure on traits that may be less important in the domesticated context. Thus, here we hypothesize that strongly deleterious mutations may have become less deleterious in domesticated populations. We test this hypothesis by estimating the distribution of fitness effects (DFE) for new amino acid changing mutations using whole-genome sequence data from 24 gray wolves and 61 breed dogs. We find that the DFE is strikingly similar across canids, with 26-28% of new amino acid changing mutations being neutral/nearly neutral (|s| < 1e-5), and 41-48% under strong purifying selection (|s| > 1e-2). Our results are robust to different model assumptions suggesting that the DFE is stable across short evolutionary timescales, even in the face of putative drastic changes in the selective pressure caused by artificial selection during domestication and breed formation. On par with previous works describing DFE evolution, our data indicate that the DFE of amino acid changing mutations depends more strongly on genome structure and organismal characteristics, and less so on shifting selective pressures or environmental factors. Given the constant DFE and previous data showing that genetic variants that differentiate wolf and dog populations are enriched in regulatory elements, we speculate that domestication may have had a larger impact on regulatory variation than on amino acid changing mutations. Significance StatementDomestication of dogs to live alongside humans resulted in a dramatic shift in the pressures of natural selection. Thus, comparing dogs and wolves offers a unique opportunity to assess how these shifts in selective pressures have impacted the fitness effects of individual mutations. In this project, we use patterns of genetic variation in dogs and wolves to estimate the distribution of fitness effects (DFE), or the proportions of amino acid changing mutations with varying fitness effects throughout the genome. Overall, we find that the DFE for amino acid changing mutations is similar between dogs and wolves. Even genes thought to be most affected by domestication show a similar DFE, suggesting that the DFE has remained stable over evolutionary time.

genetics↗

bioRxiv2023

UCLA's Competitive Edge Program Provides an Advantage to STEM Doctoral Students from Historically Excluded and Underrepresented Groups

Universities benefit from recruiting and retaining diverse students, as it leads to more creative and rigorous problem solving. Efforts to improve the diversity, equity, and inclusion of graduate education have historically been focused on recruitment but are now shifting to retaining enrolled students. A low percentage of doctoral students, particularly those from historically underrepresented groups (URGs), complete their PhD within 10 years. To increase support of incoming doctoral students from URGs, UCLA established the Competitive Edge (CE) bridge program. CE provides six weeks of professional development and research training at the start of the PhD program. We surveyed 55+ first-year doctoral students (14 CE students, eight non-CE students from URGs, and 34 well-represented (WR) students) in STEM fields to understand CEs effectiveness. We found that the CE program aided students in four areas that influence graduate student attrition: mentor/mentee relationship, socialization, finances, and preparedness. At the end of their first academic year, CE students reported that the program helped them in multiple areas relating to student success, such as mental wellbeing and sense of belonging. CE students reported a larger mean growth in seven of eight skills needed in graduate school compared to NonCE URG and WR students. Short answer responses revealed that NonCE students wished for more support in areas covered by the CE program, such as managing advising relationships and protecting mental health. Additionally, CE students received significant funding during the program. The CE programs successful model at UCLA can be adapted to improve support for underrepresented doctoral students at other institutions.

scientific communication and education↗

bioRxiv2017

Genome-wide quantification of the effects of DNA methylation on human gene regulation

Changes in DNA methylation are important in development and disease, but not all regulatory elements act in a methylation-dependent (MD) manner. Here, we developed mSTARR-seq, a high-throughput approach to quantify the effects of DNA methylation on regulatory element function. We assay MD activity in 14% of the euchromatic human genome, identify 2,143 MD regulatory elements, and predict MD activity using sequence and chromatin state information. We identify transcription factors associated with higher activity in unmethylated or methylated states, including an association between pioneer transcription factors and methylated DNA. Finally, we use mSTARR-seq to predict DNA methylation-gene expression correlations in primary cells. Our findings provide a map of MD regulatory activity across the human genome, facilitating interpretation of the many emerging associations between methylation and trait variation.

genomics↗