Genome as a mosaic

Different genomes (DNA) in cells of individuals produce genomic mosaicism¹. Is this heresy, offending the central dogma of molecular biology². Or fact, demanding quantitation? A recent paper starts bluntly with our title³.

The DNA of each somatic cell of individuals derives from parental gametes to a cell (zygote) that develops through serial replications and partitions into 2,4,8… billion new somatic cells; in the process DNA accumulates errors and damages, recombines, transposes, incorporates foreign genes and DNA-copies of numerous RNA. Hence throughout an individual’s life the DNA of its cells diverge, probably less within than between individuals. Mature neurons don’t divide: this spares duplication errors, but not the rest. In post-mortem sorted neurons Lodato et al³ find thousands of single nucleotide variants⁴, less than in UV-exposed skin, but more than in heart. Remarkably transcription alters the nontemplate strand in neurons, the template one in germ cells, inducing a use-and-lose¹ effect, sterilely reminiscent of Lamarck’s (and Darwin’s!) use-and-disuse^(4,5).

Genes&genomes are ill-defined⁶: one gene determines height in pea plants, as discovered by Mendel⁷; hundreds favor it in humans, as reported recently⁸: still height is largely inheritable. Nowadays genes are considered Read-Write (RW) systems, rather than Read-Only-Memory (ROM)⁹. Individual’s genomes vary and occasionally disappear (erythrocytes).

Genetic information is not only DNA¹⁰: zygotic genomes shed paternal decorations, recruit maternal proteins and RNA, and originate compositionally elusive (epi)genomes¹¹, recalling Flemming’s chromatin, or even Miescher’s nuclein⁷. Chromatin  includes DNA, RNA, proteins: all switch nature and partners¹². Still we launch projects (cloning¹³, serial Human Genome Projects¹⁴, stemness regeneration¹⁵, genome editing¹⁶, etc.) based on constant individual genomes. Trying to spell life as As,Cs,Gs,Ts  borders hubris, nourishes business, and mixes Prometheus and Midas¹⁷. Genomic mosaicism survives because it bridges nature and nurture¹⁸ and increases the evo-devo versatility of genomes without increasing redundancy¹². We shall not cease from exploration¹⁹: space-time variations in individual DNA are *not known because not looked for…*¹⁹. Another mad pursuit² challenging dogmas and shifting paradigms²⁰.

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