Biochemistry and Molecular Biology

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Browsing Biochemistry and Molecular Biology by Subject "African"

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    Diverse African genomes reveal selection on ancient modern human introgressions in Neanderthals
    (Current Biology, 2023-10-13) Nyambo, Thomas B.
    Comparisons of Neanderthal genomes to anatomically modern human (AMH) genomes show a history of Neanderthal-to-AMH introgression stemming from interbreeding after the migration of AMHs from Af- rica to Eurasia. All non-sub-Saharan African AMHs have genomic regions genetically similar to Neander- thals that descend from this introgression. Regions of the genome with Neanderthal similarities have also been identified in sub-Saharan African populations, but their origins have been unclear. To better understand how these regions are distributed across sub-Saharan Africa, the source of their origin, and what their distribution within the genome tells us about early AMH and Neanderthal evolution, we analyzed a dataset of high-coverage, whole-genome sequences from 180 individuals from 12 diverse sub-Saharan African populations. In sub-Saharan African populations with non-sub-Saharan African ancestry, as much as 1% of their genomes can be attributed to Neanderthal sequence introduced by recent migration, and subsequent admixture, of AMH populations originating from the Levant and North Africa. However, most Neanderthal homologous regions in sub-Saharan African populations originate from migration of AMH populations from Africa to Eurasia 250 kya, and subsequent admixture with Neanderthals, resulting in 6% AMH ancestry in Neanderthals. These results indicate that there have been multiple migration events of AMHs out of Africa and that Neanderthal and AMH gene flow has been bi-directional. Observing that genomic regions where AMHs show a depletion of Neanderthal introgression are also regions where Neanderthal genomes show a depletion of AMH introgression points to deleterious interactions between introgressed variants and background genomes in both groups—a hallmark of incipient speciation.
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    Erratum for the Research Article: “Loci associated with skin pigmentation identified in African populations”
    (Science, 2020-01-17) Nyambo, Thomas B.
    In the Research Article “Loci associated with skin pigmentation identified in African populations,” the authors made the inaccurate conclusion that mfsd12a targeting in zebrafish disrupts xanthophore function. This happened because of a misinterpretation of experimental observations, not from errors in data collection or reporting. In the original experiments, a loss of normal methylene blue staining occurred in 100% of mfsd12a −/− embryos at 5 days postfertilization. These mfsd12a −/− embryos were derived from matings between mosaic F0 founder fish (mfsd12a targeted mosaic F0 x mfsd12a targeted mosaic F0). The single guide RNAs for mfsd12a were extremely efficient, and no wild-type F1 offspring were obtained from the F0 inbreeding. Therefore, the clutches of 100% mfsd12a −/− embryos were compared with embryos derived from matings of wild-type fish (mfsd12a +/+ x mfsd12a +/+ ) in which loss of methylene blue staining was not observed. In each case, multiple clutches were analyzed from independent matings. Additionally, the wild-type breeders originated from the same colony of TAB5 fish that were used to generate fertilized eggs for Cas9 injections to generate the mfsd12a F0 founders. These reproducible results led the authors to conclude that mfsd12a was required for normal methylene blue staining of xanthophores. However, in subsequent work, the authors have observed a lack of methylene blue staining in clutches originating from other matings within their facility. They have confirmed that this lack of methylene blue staining segregates with a population variant linked to chromosome 12 within their TAB5 colony. This variant was likely present at a high-enough frequency in their mfsd12a-targeted F0 founder fish to affect the outcome. These recent data thus do not support their previous conclusion that mfsd12a functions in zebrafish pigmentation (presented in Fig. 7, A and B, of the original manuscript). Importantly, however, it does not alter the main conclusions of the manuscript that MFSD12 is associated with mammalian pigment variation in both human and mouse. The sections of the results referring to the zebrafish knockout have been removed entirely, along with the accompanying figure and cited references. Both the HTML and PDF versions of the text have been corrected.
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    Loci associated with skin pigmentation identified in African populations
    (Science, 2017-07) Nyambo, Thomas B.
    Despite the wide range of skin pigmentation in humans, little is known about its genetic basis in global populations. Examining ethnically diverse African genomes, we identify variants in or near SLC24A5, MFSD12, DDB1, TMEM138, OCA2 and HERC2 that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant at SLC24A5 was introduced into East Africa by gene flow from non-Africans. At all other loci, variants associated with dark pigmentation in Africans are identical by descent in southern Asian and Australo- Melanesian populations. Functional analyses indicate that MFSD12 encodes a lysosomal protein that affects melanogenesis in zebrafish and mice, and that mutations in melanocyte-specific regulatory regions near DDB1/TMEM138 correlate with expression of UV response genes under selection in Eurasians.