Our goal was to describe in more detail the evolutionary history of Gamma and two derived lineages (P.1.1 and P.1.2), which are part of the arms race that SARS-CoV-2 wages with its host. A total of 4,977 sequences of the Gamma strain of SARS-CoV-2 from Brazil were analyzed. We detected 194 sites under positive selection in 12 genes/ORFs: Spike, N, M, E, ORF1a, ORF1b, ORF3, ORF6, ORF7a, ORF7b, ORF8, and ORF10 . Some diagnostic sites for Gamma lacked a signature of positive selection in our study, but these were not fixed, apparently escaping the action of purifying selection. Our network analyses revealed branches leading to expanding haplotypes with sites under selection only detected when P.1.1 and P.1.2 were considered. The P.1.2 exclusive haplotype H_5 originated from a non-synonymous mutational step (H3509Y) in H_1 of ORF1a. The selected allele, 3509Y, represents an adaptive novelty involving ORF1a of P.1. Finally, we discuss how phenomena such as epistasis and antagonistic pleiotropy could limit the emergence of new alleles (and combinations thereof) in SARS-COV-2 lineages, maintaining infectivity in humans, while providing rapid response capabilities to face the arms race triggered by host immuneresponses.

Background: Spinal muscular atrophy (SMA) is mostly caused by homozygous deletions in the survival motor neuron 1 (SMN1) gene. SMN2, its paralogous gene, is a genetic modifier of the disease phenotype, and its copy number is correlated with SMA severity. The purpose of the study was to investigate the number of copies of the SMN1 and SMN2 genes in a Venezuelan population control sample and in patients with a presumptive diagnosis of SMA, besides estimating the frequency of mutation carriers in the population. Results: SMN1 and SMN2 gene copies were assessed in 49 Venezuelan dweller unrelated normal individuals and in 94 subjects from 29 families with a SMA presumptive diagnosis, using the quantitative PCR method. A SMN1 deletion carrier frequency of 0.01 and 0.163 of homozygous absence of the SMN2 gene were found in the Venezuelan control sample. Deletion of SMN1 exon 7 was confirmed in 15 families; the remaining 14 index cases had two SMN1 copies and a heterogeneous phenotype not attributable to SMN deletions. Based on clinical features of the index cases and the SMN2 copy number, a positive phenotype-genotype correlation was demonstrated. No disease geographical aggregation was found in the country. Conclusion: The frequency of carriers of the deletion of exon 7 in SMN1 in the Venezuelan control population was similar to that observed in populations worldwide, while the frequency of 0 copies of the SMN2 gene (16.3 %) seems to be relatively high. All these findings have pertinent implications for the diagnosis and genetic counseling on SMA in Venezuela.

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