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Neo-Darwinism is generally used to describe any integration of Darwin's theory of evolution by natural selection with Gregor Mendel's theory of genetics. Mostly used to refer to evolutionary theory from either 1895 (for the combinations of Darwin's and Weismann's theories evolution) or 1942 Modern synthesis (20th century). Though it can refer to any new Darwinian/Mendel-based theory such as the current evolutionary theory. The term Neo-Darwinism marks the combination of natural selection and genetics, and as it has variously been modified since it was first proposed.

Early usage
Darwin's theory of evolution by natural selection as publish in 1859, provided a selection mechanism for evolution, but not a trait transfer mechanism. Lamarckism was still a very popular candidate for this. As part of the disagreement about the mechanisms of evolution, Samuel Butler called the British naturalist Alfred Russel Wallace strongly opposition to Lamarckism, for Neo-Darwinism. Weismann and Wallace rejected the Lamarckian idea of inheritance of acquired characteristics that even Darwin took for granted. The basis for the complete rejection of Lamarckism was Weismann's germ plasm theory. Weismann realised that the cells that produce the germ plasm, or gametes (such as sperm and eggs in animals), separate from the somatic cells that go on to make other body tissues at an early stage in development. Since he could see no obvious means of communication between the two, he asserted that the inheritance of acquired characteristics was therefore impossible; a conclusion now known as the Weismann barrier.

It is however usually George Romanes, that is credited for the first use of the word in a scientific context. Romanes used the term to describe the combination of natural selection and the August Weismann's germ plasm theory,that evolution occurs solely through natural selection, and not by the inheritance of acquired characteristics resulting from use or disuse, making the word to mean, 'Darwinism without Lamarckism'

Following the development, from about 1918 to 1947, of the modern synthesis of evolutionary biology, the term neo-Darwinian stated to be to refer to that contemporary evolutionary theory.

Any current version of evolutionary thinking
Biologists however have not limited their application of the term neo-Darwinism to the historical modern synthesis. For example, Ernst Mayr wrote in 1984 that "the term neo-Darwinism for the synthetic theory [the modern synthesis of the early 20th century] is wrong, because the term neo-Darwinism was coined by Romanes in 1895 as a designation of Weismann's theory".

Publications such as Encyclopædia Britannica similarly use neo-Darwinism to refer to current evolutionary theory, not the version current during the early 20th century synthesis. Richard Dawkins and Stephen Jay Gould have used the term in their writings and lectures to denote the forms of evolutionary biology that were contemporary when they were writing.