Pseudogene

About: Pseudogene is a research topic. Over the lifetime, 5528 publications have been published within this topic receiving 336634 citations. The topic is also known as: Ψ & pseudogenes.

Fixation of the human-specific CMP-N-acetylneuraminic acid hydroxylase pseudogene and implications of haplotype diversity for human evolution.

Abstract: The human CMP-N-acetylneuraminic acid hydroxylase gene (CMAH) suffered deletion of an exon that encodes an active center for the enzyme ∼3.2 million years ago (MYA). We analyzed a 7.3-kb intronic region of 132 CMAH genes to explore the fixation process of this pseudogene and the demographic implication of its haplotype diversity. Fifty-six variable sites were sorted into 18 different haplotypes with significant linkage disequilibrium. Despite the rather low nucleotide diversity, the most recent common ancestor at CMAH dates to 2.9 MYA. This deep genealogy follows shortly after the original exon deletion, indicating that the deletion has fixed in the population, although whether this fixation was facilitated by natural selection remains to be resolved. Remarkable features are exceptionally long persistence of two lineages and the confinement of one lineage in Africa, implying that some African local populations were in relative isolation while others were directly involved in multiple African exoduses of the genus Homo. Importantly, haplotypes found in Eurasia suggest interbreeding between then-contemporaneous human species. Although population structure within Africa complicates the interpretation of phylogeographic information of haplotypes, the data support a single origin of modern humans, but not with complete replacement of archaic inhabitants by modern humans.

Comparative Proteomics Reveals a Significant Bias Toward Alternative Protein Isoforms with Conserved Structure and Function

Abstract: Advances in high-throughput mass spectrometry are making proteomics an increasingly important tool in genome annotation projects. Peptides detected in mass spectrometry experiments can be used to validate gene models and verify the translation of putative coding sequences (CDSs). Here, we have identified peptides that cover 35% of the genes annotated by the GENCODE consortium for the human genome as part of a comprehensive analysis of experimental spectra from two large publicly available mass spectrometry databases. We detected the translation to protein of "novel" and "putative" protein-coding transcripts as well as transcripts annotated as pseudogenes and nonsense-mediated decay targets. We provide a detailed overview of the population of alternatively spliced protein isoforms that are detectable by peptide identification methods. We found that 150 genes expressed multiple alternative protein isoforms. This constitutes the largest set of reliably confirmed alternatively spliced proteins yet discovered. Three groups of genes were highly overrepresented. We detected alternative isoforms for 10 of the 25 possible heterogeneous nuclear ribonucleoproteins, proteins with a key role in the splicing process. Alternative isoforms generated from interchangeable homologous exons and from short indels were also significantly enriched, both in human experiments and in parallel analyses of mouse and Drosophila proteomics experiments. Our results show that a surprisingly high proportion (almost 25%) of the detected alternative isoforms are only subtly different from their constitutive counterparts. Many of the alternative splicing events that give rise to these alternative isoforms are conserved in mouse. It was striking that very few of these conserved splicing events broke Pfam functional domains or would damage globular protein structures. This evidence of a strong bias toward subtle differences in CDS and likely conserved cellular function and structure is remarkable and strongly suggests that the translation of alternative transcripts may be subject to selective constraints.

Inactivation dates of the human and guinea pig vitamin C genes

Abstract: The capacity to biosynthesize ascorbic acid has been lost in a number of species including primates, guinea pigs, teleost fishes, bats, and birds. This inability results from mutations in the GLO gene coding for L-gulono-γ-lactone oxidase, the enzyme responsible for catalyzing the last step in the vitamin C biosynthetic pathway. We analyzed available primate and rodent GLO gene sequences to determine their evolutionary history. We used a method based on sequence comparisons of lineages with and without functional GLO genes to calculate inactivation dates of 61 and 14 MYA for the primate and guinea pig genes, respectively. These estimates are consistent with previous phylogeny-based estimates. An analysis of transposable element distribution in the primate and rodent GLO sequences did not reveal conclusive evidence that illegitimate recombination between repeats has contributed to the loss of exons in the primate and guinea pig genes.