Most recent common ancestor | EPFL Graph Search

In biology and genetic genealogy, the most recent common ancestor (MRCA), also known as the last common ancestor (LCA) or concestor, of a set of organisms is the most recent individual from which all the organisms of the set are descended. The term is also used in reference to the ancestry of groups of genes (haplotypes) rather than organisms. The MRCA of a set of individuals can sometimes be determined by referring to an established pedigree. However, in general, it is impossible to identify the exact MRCA of a large set of individuals, but an estimate of the time at which the MRCA lived can often be given. Such time to most recent common ancestor (TMRCA) estimates can be given based on DNA test results and established mutation rates as practiced in genetic genealogy, or by reference to a non-genetic, mathematical model or computer simulation. In organisms using sexual reproduction, the matrilineal MRCA and patrilineal MRCA are the MRCAs of a given population considering only matrilineal and patrilineal descent, respectively. The MRCA of a population by definition cannot be older than either its matrilineal or its patrilineal MRCA. In the case of Homo sapiens, the matrilineal and patrilineal MRCA are also known as "Mitochondrial Eve" (mt-MRCA) and "Y-chromosomal Adam" (Y-MRCA) respectively. The age of the human MRCA is unknown. It is no greater than the age of either the Y-MRCA or the mt-MRCA, estimated at around 200,000 years. Unlike in pedigrees of individual humans or domesticated lineages where historical parentage is known, in the inference of relationships among species or higher groups of taxa (systematics or phylogenetics), ancestors are not directly observable or recognizable. They are inferences based on patterns of relationship among taxa inferred in a phylogenetic analysis of extant organisms and/or fossils. The last universal common ancestor (LUCA) is the most recent common ancestor of all current life on Earth, estimated to have lived some 3.5 to 3.8 billion years ago (in the Paleoarchean).

Beyond silence : a functional and evolutionary study of KRAB zinc finger proteins

Pierre-Yves Joseph Laurent Helleboid

Transposable elements (TEs) are genetic units capable of spreading within the genomes of their host. TEs contribute a readily recognizable 45% of the human DNA, reflecting in part their co-option for some as source of protein-coding sequences, for others as regulators of genome architecture and expression. Nevertheless, new TE integrants can occasionally cause diseases. The KZFP/KAP1 (KRAB-Zinc Finger Protein /KRAB-associated Protein 1) system plays a major role in the transcriptional control of TEs. Encoded in the hundreds by the genomes of most higher vertebrates, KZFPs are endowed with a N-terminal KRAB (KruÌppel- associated box) domain, some of which can recruit KAP1, and a C-terminal array of zinc fingers (ZNF) with polynucleotide binding potential. When we started this work, KZFP genes were thought to be restricted to tetrapods, and a few of their products had been found to tether KAP1 and associated heterochromatin-inducing factors to TE-derived sequences during mouse or human early embryogenesis, resulting in the deposition at these loci of H3K9me3 (histone 3 trimethylated on lysine 9) and DNA methylation, two repressive marks. Additionally, the KZFP/KAP1 system had been implicated in events as diverse as imprinting, cell differentiation and metabolic homeostasis. In order to gain insight into the biology of human KZFPs, we first performed a large-scale identification of their genomic targets. We found that the majority was enriched at TEs, where they bound to regions also recognized by other TFs. Accordingly, many KZFP-targeted TE loci displayed differential chromatin patterns in human tissues, consistent notably with their putative role of cell-specific enhancers. This strongly suggests that KZFPs participate in orchestrating TE-modulated regulatory networks. Finally, we could trace KZFP genes to a common ancestor of the coelacanth, lungfishes and tetrapods, and determined that their evolutionary emergence was most often contemporaneous to that of their TE targets, with signs supporting both an arms race and a domestication model. To pursue this exploration, we analyzed the protein partners of more than a hundred human KZFPs. We could observe that the interactome of evolutionarily recent KZFPs mainly comprised KAP1 and associated effectors, whereas that of more ancient family members, conserved from marsupials to sauropsids, tended not to associate with KAP1 and were likely to engage in interactions with more original factors, including proteins related to RNA processing or genome architecture. While these results suggested that KAP1 binding might have been a late emerging property of KZFPs, we could demonstrate that KRAB domains derived from Latimeria chalumnae associated with the cognate KAP1 protein, albeit not with its human orthologue. These results support a model whereby KZFPs first emerged as TE- controlling repressors, were continuously renewed by turnover of their hostsâ TE loads, and occasionally produced derivatives that escaped this evolutionary flushing by development and exaptation of novel functions. In sum, this work provides important insights into the evolutionary history and biological function of KRAB zinc finger proteins, the largest family of transcriptional regulators encoded by human and other higher vertebrates.

EPFL2019

Beyond silence : a functional and evolutionary study of KRAB zinc finger proteins

Pierre-Yves Joseph Laurent Helleboid

EPFL2019