Biology subjects

Nunes, K.

Publications and source records attributed to Nunes, K..

3 recordsLinked to original sources

bioRxiv2025

Rapid expansion of synaptic complexity as a key contributor to cognitive growth in early humans

Primates have been evolving for over 50 million years. At some point, humans made an unusually large evolutionary leap, giving rise to abilities like the creation of tools, intricate art and complex language. The neuronal synapse, a key player in information processing and brain plasticity, has largely been ignored as a potential factor in this process. Here we used the genomic databases of ancestral hominins to compare the expression levels of 995 genes expressed in the human nervous system among archaic (6 Neanderthal, 2 Denisovan) and modern humans (62 African Modern Human). We searched in the 95th top p-value for variants whose derived alleles had a frequency [≥]90% in modern and <10% in archaic humans. We then used the STRING database to perform protein-protein interaction networks on the 95th top p-value for the variants. We identified genetic variants in 15 genes, and in two (STX16 and UBASH3B), the allele frequency was significantly higher in modern versus archaic humans. These genes have previously been associated with critical cellular (proliferation, differentiation, migration, survival) and synaptic (exocytosis, synaptic vesicle fusion) processes, supporting the idea that changes in synaptic structure and function may have played a key role in the development of human cognition.

evolutionary biology↗

bioRxiv2021

Population structure in the MHC region

In his 1972 "The apportionment of human diversity", Lewontin showed that, when averaged over loci, genetic diversity is predominantly attributable to differences among individuals within populations. However, selection on specific genes and genomic regions can alter the apportionment of diversity. We examine genetic diversity at the HLA loci, located within the MHC region. HLA genes code for proteins that are critical to adaptive immunity and are well-documented targets of balancing selection. The SNPs within HLA genes show strong signatures of balancing selection on large timescales and are broadly shared among populations, with low FST values. However, when we analyze haplotypes defined by these SNPs (i.e., which define "HLA alleles"), we find marked differences in frequencies between geographic regions. These differences are not reflected in the FST values because of the extreme polymorphism at HLA loci, illustrating challenges in interpreting FST. Differences in the frequency of HLA alleles among geographic regions are relevant to bone-marrow transplantation, which requires genetic identity at HLA loci between patient and donor. We explore the case of Brazils bone-marrow registry, where a deficit of enrolled volunteers with African ancestry reduces the chance of finding donors for individuals with an MHC region of African ancestry.

genetics↗

bioRxiv2020

Whole-genome sequencing of 1,171 elderly admixed individuals from the largest Latin American metropolis (Sao Paulo, Brazil)

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enabled identifying ~2,000 novel mobile element insertions, nearly 5Mb of genomic segments absent from human genome reference, and over 140 novel alleles from HLA genes. We reclassified and curated nearly four hundred variant's pathogenicity assertions in genes associated with dominantly inherited Mendelian disorders and calculated the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observed that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS.

genomics↗