RESUMEN
Searches for the genetic underpinnings of uniquely human traits have focused on human-specific divergence in conserved genomic regions, which reflects adaptive modifications of existing functional elements. However, the study of conserved regions excludes functional elements that descended from previously neutral regions. Here, we demonstrate that the fastest-evolved regions of the human genome, which we term "human ancestor quickly evolved regions" (HAQERs), rapidly diverged in an episodic burst of directional positive selection prior to the human-Neanderthal split, before transitioning to constraint within hominins. HAQERs are enriched for bivalent chromatin states, particularly in gastrointestinal and neurodevelopmental tissues, and genetic variants linked to neurodevelopmental disease. We developed a multiplex, single-cell in vivo enhancer assay to discover that rapid sequence divergence in HAQERs generated hominin-unique enhancers in the developing cerebral cortex. We propose that a lack of pleiotropic constraints and elevated mutation rates poised HAQERs for rapid adaptation and subsequent susceptibility to disease.
Asunto(s)
Hominidae , Hombre de Neandertal , Animales , Humanos , Hominidae/genética , Secuencias Reguladoras de Ácidos Nucleicos , Hombre de Neandertal/genética , Genoma Humano , GenómicaRESUMEN
Despite prevalent preventative methods of human papillomavirus (HPV), cervical cancer remains the foremost cause of cancer-related death among women of reproductive age in Western Kenya. HPV self-sampling is a preventative measure that can improve accessibility and availability to cervical cancer screening. Correct education about HPV is crucial to combating stigma and increasing HPV screening uptake. In this study, we evaluated the workflow impact of a video-assisted HPV education to promote self-sampling in clinical settings in Kisumu, Kenya. We conducted a descriptive workflow study nested in a two-part cluster-randomized control trial in six government-supported health clinics in Kisumu County. We observed the workflow of HPV screening video-assisted and standard health educations. and evaluated community and clinic health assistant facilitation (CCHA), duration, and feasibility of the intervention. Thirty HPV screening-eligible women who participated in the video intervention were recruited for three focus group discussions (FGDs). The FGDs aimed to better understand women's experience with the video screening, their impressions on the content, and feedback about intervention logistics. Across 33 observations, 16.5 women per day watched the educational video at intervention clinics, and 14 women per day heard standard Ministry of Health cervical cancer prevention education talks at control clinics. Sixty-three percent of women participated in HPV self-sampling in the intervention sites, compared to forty-six percent who screened after standard health talks at control sites. The workflow observations identified variable video projection and viewing space, access to power supply, and CCHA availability and ability to utilize the projector as major factors impacting education workflow. Women in FGDs appreciated the video modality, length of video, and education location. HPV video education is a suitable intervention, with further research recommended to determine the viability of sustainably implementing the intervention in a clinic environment. This research is fully funded by the Duke University Global Health Institute.