A nuclear gene is a gene whose physical DNA nucleotide sequence is located in the cell nucleus of a eukaryote. The term is used to distinguish nuclear genes from genes found in mitochondria or chloroplasts. The vast majority of genes in eukaryotes are nuclear. Mitochondria and plastids evolved from free-living prokaryotes into current cytoplasmic organelles through endosymbiotic evolution. Mitochondria are thought to be necessary for eukaryotic life to exist. They are known as the cell's powerhouses because they provide the majority of the energy or ATP required by the cell. The mitochondrial genome (mtDNA) is replicated separately from the host genome. Human mtDNA codes for 13 proteins, most of which are involved in oxidative phosphorylation (OXPHOS). The nuclear genome encodes the remaining mitochondrial proteins, which are then transported into the mitochondria. The genomes of these organelles have become far smaller than those of their free-living predecessors. This is mostly due to the widespread transfer of genes from prokaryote progenitors to the nuclear genome, followed by their elimination from organelle genomes. In evolutionary timescales, the continuous entry of organelle DNA into the nucleus has provided novel nuclear genes. Though separated from one another within the cell, nuclear genes and those of mitochondria and chloroplasts can affect each other in a number of ways. Nuclear genes play major roles in the expression of chloroplast genes and mitochondrial genes. Additionally, gene products of mitochondria can themselves affect the expression of genes within the cell nucleus. This can be done through metabolites as well as through certain peptides trans-locating from the mitochondria to the nucleus, where they can then affect gene expression. Eukaryotic genomes have distinct higher-order chromatin structures that are closely packaged functional relates to gene expression. Chromatin compresses the genome to fit into the cell nucleus, while still ensuring that the gene can be accessed when needed, such as during gene transcription, replication, and DNA repair.

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